Page
1
of
125
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
June
21,
2006
MEMORANDUM
SUBJECT:
ORGANIC
ARSENICS:
Final
HED
Combined
Chapter
of
the
Reregistration
Eligibility
Decision
Document
(
RED).
Organic
Arsenics:
Cacodylic
Acid
&
Salt,
PC
Code
012501/
012502;
MSMA,
PC
Code
013802;
DSMA,
PC
Code
013803;
and
CAMA,
PC
Code
013806.
DP
Barcode:
D329694
FROM:
Charles
Smith,
Risk
Assessor/
Environmental
Scientist
Reregistration
Branch
2
Health
Effects
Division
(
7509P)
AND
Anna
Lowit,
Ph.
D.
Sherrie
Kinard
Yvonne
Barnes
Ruth
Allen
Health
Effects
Division
(
7509P)
AND
Keara
Moore
Environmental
Fate
and
Effects
Division
(
7507P)

THRU:
Alan
Nielsen,
Branch
Senior
Scientist
William
J.
Hazel,
Ph.
D.,
Branch
Chief
Reregistration
Branch
2
Health
Effects
Division
(
7509P)

TO:
Lance
Wormell,
CRM
Reregistration
Branch
2
Special
Review
and
Reregistration
Division
(
7508P)

The
attached
post­
Science
Advisory
Board
(
SAB)
review
of
the
Human
Health
Assessment
for
the
organic
arsenic
RED
document
was
generated
as
part
of
Phase
4
of
the
public
participation
process.
The
Health
Effects
Division's
(
HED)
Final
chapter
reflects
the
comments
received
during
the
Phase
3
public
comment
period.
This
risk
assessment
document
includes
the
potential
individual
chemical
contributions
to
human
health
risk
of
cacodylic
acid
(
DMA)
and
its
salt,
monosodium
methanearsonate
(
MSMA),
disodium
methanearsonate
(
DSMA),
and
calcium
acid
methanearsonate
(
CAMA).
This
assessment
also
includes
a
review
of
the
aggregate
human
health
assessment
for
the
potential
combined
exposures
to
a
common
transformation
product
Page
2
of
125
from
the
use
of
the
organic
arsenicals.
Potential
risks
from
exposure
to
inorganic
arsenic
resulting
from
the
use
of
the
organic
arsenicals
are
also
discussed.
This
chapter
includes
a
summary
of
the
product
chemistry
review
from
Yvonne
Barnes,
residue
chemistry
review
from
Yvonne
Barnes/
Sherrie
Kinard/
Bonnie
Cropp­
Kohlligian,
dietary
risk
assessment
from
Sherrie
Kinard,
toxicology
review
from
Anna
Lowit,
occupational
exposure
and
risk
assessment
from
Charles
Smith,
incidence
review
from
Ruth
Allen,
environmental
fate
and
drinking
water
exposures
from
Keara
Moore
[
Environmental
Fate
and
Effects
Division
(
EFED)],
as
well
as
risk
assessment
and
characterization
from
Charles
Smith.

This
assessment
relies
in
part
on
data
from
studies
in
which
adult
human
subjects
were
intentionally
exposed
to
a
pesticide.
These
studies,
listed
below,
have
been
determined
to
require
a
review
of
their
ethical
conduct.
The
listed
studies
have
either
received
the
appropriate
review
or
are
in
the
process
of
being
ethically
reviewed.

Buchet,
J.
P.,
Lauwerys,
R.,
&
Roels,
H.
(
1981).
Comparison
of
the
urinary
excretion
of
arsenic
metabolites
after
a
single
oral
dose
of
sodium
arsenite,
monomethylarsonate,
or
dimethylarsinate
in
man.
International
Archives
of
Occupational
and
Environmental
Health,
48(
1),
71­
79.

Johnson,
L.
R.,
&
Farmer,
J.
G.
(
1991).
Use
of
human
metabolic
studies
and
urinary
arsenic
speciation
in
assessing
arsenic
exposure.
Bulletin
of
Environmental
Contamination
&
Toxicology,
46,
53­
61.

Marafante,
E.,
Vahter,
M.,
Norin,
H.,
Envall,
J.,
Sandstrom,
M.,
Christakopoulos,
A.,
Ryhage,
R.
(
1987).
Biotransformation
of
dimethylarsinic
acid
in
mouse,
hamster
and
man.
Journal
of
Applied
Toxicology,
7(
2),
111­
117.

Carbaryl
Mixer/
Loader/
Applicator
Exposure
Study
During
Application
of
RP­
2
Liquid
(
21%),
Sevin
Ready
to
Use
Insect
Spray
or
Sevin
10
Dust
to
Home
Garden
Vegetables.
MRID
444598­
01
D.
Merricks.
(
1997).

Integrated
Report
for
Evaluation
of
Potential
Exposures
to
Homeowners
and
Professional
Lawn
Care
Operators
Mixing,
Loading,
and
Applying
Granular
and
Liquid
Pesticides
to
Residential
Lawns.
MRID
449722­
01.
D.
Klonne.
(
1999).

The
PHED
Task
Force,
1995.
The
Pesticide
Handler
Exposure
Database
(
PHED),
Version
1.1.
Task
Force
members
Health
Canada,
U.
S.
Environmental
Protection
Agency,
and
the
National
Agricultural
Chemicals
Association,
released
February
1995.

cc:
Tina
Levine
Jack
Housenger
Debbie
Edwards
William
Hazel
Margaret
Rice
Page
3
of
125
Table
of
Contents
Table
of
Contents                              ..................
3
Preface
....................................................................................................................................................
5
1.0
Executive
Summary...........................................................................................................................
6
2.1
Summary
of
Registered
Uses
.......................................................................................................
10
2.2
Structure
and
Nomenclature.........................................................................................................
13
Cacodylic
Acid
&
Sodium
Cacodylate...........................................................................................
13
MSMA/
DSMA/
CAMA.................................................................................................................
13
3.1
Comparative
Metabolic
Profile
....................................................................................................
23
3.1.1
In
vivo
Metabolism
Studies
...................................................................................................
25
3.1.2
In
vitro
Studies
.....................................................................................................................
29
3.2
Nature
of
the
Residue
in
Foods
....................................................................................................
29
3.2.1
Description
of
Primary
Crop
Metabolism..............................................................................
29
3.3
Environmental
Fate......................................................................................................................
30
3.3.1
Degradation
(
Metabolites)
....................................................................................................
31
3.3.2
Mobility
...............................................................................................................................
32
3.3.3
Soil
Buildup/
Persistence
.......................................................................................................
32
4.0
Hazard
Characterization/
Assessment................................................................................................
34
4.1
Overview
and
Background...........................................................................................................
34
4.2
MMA
..........................................................................................................................................
35
4.2.1
Database
Summary
...............................................................................................................
35
4.2.2
Toxicological
Effects
............................................................................................................
36
4.2.3
FQPA
Hazard
Considerations
...............................................................................................
44
4.2.4
Dose­
Response,
Hazard
Identification
and
Toxicity
Endpoint
Selection
................................
44
4.2.4.1
Acute
Reference
Dose
(
aRfD)
­
General
Population.......................................................
46
4.2.4.2
Chronic
Reference
Dose
(
cRfD).....................................................................................
46
4.2.4.3
Incidental
Oral
Exposure
(
Short
Term)
..........................................................................
46
4.2.4.4
Incidental
Oral
Exposure
(
Intermediate
Term)
...............................................................
47
4.2.4.5
Dermal
Exposure
(
Short
and
Intermediate
Term)
...........................................................
47
4.2.4.6
Inhalation
Exposure
(
Short
and
Intermediate
Term)
.......................................................
47
4.2.5
Recommendation
for
Aggregate
Exposure
Risk
Assessments
................................................
47
4.2.6
Classification
of
Carcinogenic
Potential
................................................................................
47
4.2.7
Endocrine
Disruption............................................................................................................
49
4.3
DMA...........................................................................................................................................
49
4.3.1
Database
Summary
...............................................................................................................
49
4.3.2
Toxicological
Effects
............................................................................................................
49
4.3.3
FQPA
Hazard
Considerations
...............................................................................................
52
4.3.4
Dose­
Response,
Hazard
Identification
and
Toxicity
Endpoint
Selection
................................
53
4.3.4.1
Acute
Reference
Dose
(
aRfD)
­
General
Population
&
Acute
Incidental
Oral
Exposure..
55
4.3.4.2
Chronic
Reference
Dose
(
cRfD)
&
Incidental
Oral
Exposure
.........................................
55
4.3.4.3
Dermal
Exposure
(
Short­
and
Intermediate­
Term)..........................................................
55
4.3.5
Recommendation
for
Aggregate
Exposure
Risk
Assessments
................................................
57
4.3.6
Classification
of
Carcinogenic
Potential
................................................................................
57
4.3.7
Endocrine
Disruption............................................................................................................
57
5.1
Incident
Reports...........................................................................................................................
58
5.1.1
Cacodylic
Acid
Incidents
......................................................................................................
58
5.1.2
MSMA/
DSMA
Incidents
......................................................................................................
59
5.1.3
CAMA
Incidents
..................................................................................................................
59
5.2
Other
...........................................................................................................................................
59
6.0
Exposure
Characterization/
Assessment
............................................................................................
59
Page
4
of
125
6.1
Dietary
Exposure/
Risk
Pathway...................................................................................................
59
6.1.1
Residue
Profile
.....................................................................................................................
60
6.1.2
Dietary
Risk
Assessment/
Characterization
............................................................................
62
6.1.2.1
Acute
Dietary
Exposure
Results
and
Characterization
....................................................
63
6.1.2.2
Chronic
Dietary
Exposure
Results
and
Characterization.................................................
64
6.1.2.3
Dietary
Risk
Results/
Discussion
....................................................................................
64
6.2
Water
Exposure/
Risk
Pathway
.....................................................................................................
69
6.2.1
Surface
Water
Modeling
for
Drinking
Water
Estimates
.........................................................
70
6.2.1.1
Inputs/
Characterization..................................................................................................
71
6.2.2
Drinking
Water
from
Ground
Water......................................................................................
73
6.3
Residential
(
Non­
occupational)
Exposure/
Risk
Pathway
..............................................................
73
6.3.1
Residential
Handler
Exposures
and
Risks..............................................................................
74
6.3.1.1
Inputs
and
Assumptions
for
Residential
Handler
Risks...................................................
74
6.3.1.2
Summary
of
Residential
Handler
Risks
..........................................................................
78
6.3.2
Residential/
Non­
occupational
Postapplication
Exposures
and
Risks
......................................
79
6.3.2.1
Residential
Postapplication
Inputs
and
Assumptions
......................................................
79
6.3.2.2
Residential/
Non­
occupational
Postapplication
Risk
Summary........................................
80
7.0
Aggregate
Risk
Assessments
and
Risk
Characterization
...................................................................
84
7.1
Acute
Aggregate
Risk..................................................................................................................
85
7.2
Short­
term
Aggregate
Risk...........................................................................................................
87
7.3
Intermediate­
term
Aggregate
Risk................................................................................................
89
7.4
Long­
term
Aggregate
Risk...........................................................................................................
89
7.5
Aggregate
Cancer
Risk
................................................................................................................
90
7.6
Aggregate
Risk
Summary
............................................................................................................
90
7.7
"
Total
Arsenic"
and
Exposure
to
Inorganic
Arsenic
.....................................................................
91
7.7.1
Dietary
.................................................................................................................................
91
7.7.2
Drinking
Water.....................................................................................................................
92
7.7.3
Residential
Postapplication
Exposure....................................................................................
92
8.0
Cumulative
Risk
Characterization/
Assessment
.................................................................................
94
9.0
Occupational
Exposure/
Risk
Pathway
..............................................................................................
95
9.1
Short/
Intermediate­
term
Occupational
Handler
Exposure
and
Risk...............................................
96
9.1.1
Inputs/
Assumptions
into
Handler
Exposure/
Risk
Estimates
...................................................
96
9.1.2
Summary
of
Occupational
Handler
Risk
Concerns
..............................................................
117
9.2
Occupational
Postapplication
Exposures
and
Risk
Estimates
......................................................
117
9.2.1
Occupational
Postapplication
Scenarios,
Inputs,
and
Assumptions
......................................
117
9.2.2
Summary
of
Occupational
Postapplication
Risk
Concerns...................................................
118
10.0
Data
Needs
and
Label
Requirements
............................................................................................
120
10.1
Product
Chemistry
...................................................................................................................
120
10.2
Residue
Chemistry...................................................................................................................
120
10.3
Occupational/
Residential
Exposure
..........................................................................................
120
11.0
References
...................................................................................................................................
122
12.0
Attachments.................................................................................................................................
124
Page
5
of
125
Preface
The
Food
Quality
Protection
Act
of
1996
requires
that
EPA's
Office
of
Pesticide
Programs
review
the
safety
of
all
existing
pesticide
tolerances
(
the
legal
limit
set
on
the
maximum
amount
of
pesticides
that
may
remain
in
or
on
foods)
by
August
2006.
As
part
of
this
tolerance
reassessment
process,
the
risk
assessment
on
the
organic
arsenical
pesticides
is
being
updated.
There
are
four
registered
organic
arsenical
pesticides:
cacodylic
acid
(
dimethylarsinic
acid,
DMA)
and
its
sodium
salt
(
sodium
cacodylate);
monosodium
methanearsonate
(
MSMA);
disodium
methanearsonate
(
DSMA);
and
calcium
acid
methanearsonate
(
CAMA).
One
other
organic
arsenical,
arsanilic
acid
(
PC
129005),
is
not
included
in
this
assessment.
Arsanilic
acid
is
a
plant
growth
regulator
with
a
registration
(
expiration
02/
28/
2001)
for
experimental
use
(
180.550)
in
Florida
on
grapefruit
(
tolerance
2
ppm).
For
ease
of
discussion
the
sodium
salt
of
cacodylic
acid
and
cacodylic
acid
are
treated
as
one
and
will
be
referred
to
as
dimethylarsinic
acid
(
DMA),
and
MSMA,
DSMA,
and
CAMA
will
be
referred
to
as
monomethylarsinic
acid
(
MMA).
In
cases
where
chemical­
specific
uses,
risks,
or
other
issues
are
being
discussed,
the
specific
pesticide
name
(
MSMA,
DSMA,
and
CAMA)
will
be
used.
DMA
and
MMA
can
occur
as
two
different
valence
states.
Unless
noted,
DMA
and
MMA
refer
to
the
+
5
valence
state
(
e.
g.,
DMAV,
MMAV).
Section
4.0
of
this
document
describes
the
mode
of
action
for
the
development
of
rat
bladder
tumors
following
oral
exposure
to
DMA.
One
of
the
key
events
in
this
mode
of
action
is
the
reduction
of
DMAV
to
a
toxic
metabolite,
DMAIII.
Thus,
in
Section
4.0,
as
necessary
the
specific
valence
states
of
DMA
are
noted.

As
part
of
the
reassessment
of
the
organic
arsenic
herbicides,
new
studies
on
the
metabolism
and
the
animal
cancer
mode
of
action
of
DMA
were
evaluated.
These
studies
were
the
focus
of
a
special
issue
paper
(
USEPA,
2005a)
presented
to
the
Science
Advisory
Board
(
SAB)
September
12­
13,
2005.
The
paper
focused
on
the
carcinogenic
mode
of
action
in
animals
and
whether
the
rat
tumor
data
should
be
used
to
estimate
human
potential
risk
and
if
so,
how
an
understanding
of
the
mode
of
action
informs
the
dose
response
extrapolation
for
cancer
risk
assessment.
Based
on
the
deliberations
of
the
SAB,
the
Agency
made
appropriate
revisions
to
the
issue
paper
(
USEPA,
2005b).
The
current
risk
assessment
reflects
these
revisions,
in
addition
to
the
revisions
that
were
made
based
on
the
comments
received
during
the
Phase
3
public
comment
period.
Page
6
of
125
1.0
Executive
Summary
The
Special
Review
and
Registration
Division
requested
that
HED
conduct
a
human
health
aggregate
risk
assessment/
determination
of
safety
for
potential
aggregate
exposures
to
residues
of
arsenic
compounds
from
organic
arsenical
herbicide
use.
The
Federal
Insecticide,
Fungicide,
and
Rodenticide
Act
(
FIFRA)
and
the
Federal
Food,
Drug,
and
Cosmetic
Act
(
FFDCA)
were
amended
by
the
Food
Quality
Protection
Act
(
FQPA)
of
1996.
The
FQPA
differs
from
FIFRA
and
FFDCA
by
the
mandate
to
consider
available
information
concerning
the
cumulative
effects
of
such
residues
and
other
substances
that
have
a
common
metabolite
(
or
common
mechanism)
when
performing
tolerance
assessments
for
pesticides.

This
organic
arsenic
risk
assessment
document
captures
the
potential
human
health
risk
from
both
single
chemical
exposures
and,
overlapping,
or
co­
occurring,
exposures
to
multiple
organic
arsenical
herbicides
that
can
biotransform
to
a
common
arsenic
species.
This
assessment
includes
the
four
registered
organic
arsenical
herbicides:
cacodylic
acid
(
dimethylarsinic
acid;
a.
k.
a.
DMA)
and
its
sodium
salt
(
sodium
cacodylate);
monosodium
methanearsonate
(
MSMA);
disodium
methanearsonate
(
DSMA);
and
calcium
acid
methanearsonate
(
CAMA).
Reregistration
of
DMA
is
being
supported
by
Luxembourg­
Pamol,
Inc.
Reregistration
of
the
MMA
salts
is
being
supported
by
the
MAA
Task
Force
(
MAATF),
which
consists
of
APC
Holdings/
Drexel
Chemical
Company,
KMG­
Bernuth,
Inc.,
and
Luxembourg­
Pamol,
Inc.

DMA
is
a
defoliant
(
non­
selective)
used
primarily
on
cotton
and
to
a
much
lesser
extent,
on
nonbearing
citrus,
with
some
non­
agricultural
(
including
golf
courses,
recreational
areas,
and
rightsof
way)
and
residential
uses
in
weed
control
and
lawn
renovation.
MSMA
and
DSMA
are
selective
pre­
and
post­
emergence
herbicides
used
on
cotton,
non­
bearing
citrus
and
nuts,
golf
courses,
recreational
areas
including
schoolyards,
lawns,
and
rights­
of­
way.
CAMA
is
a
selective
post­
emergence
herbicide
registered
for
nonfood/
feed
uses
on
golf
courses,
recreational
areas
including
schoolyards,
lawns,
and
rights­
of­
way.
CAMA
has
no
registered
food
uses.

MSMA,
DSMA,
and
CAMA
are
salts
of
MMA
and
readily
dissociate
to
MMA
in
water.
HED
has
concluded
that
the
primary
residues
of
concern
resulting
from
the
herbicidal
use
of
organic
arsenics
are
MMA
and
DMA
per
se
and
their
environmental
transformation
products;
MMA,
DMA
and
inorganic
arsenic
(
iAs).
HED
and
our
partners
in
EFED
recognize
that
over
time,
and
depending
on
the
environmental
conditions
present,
organic
arsenicals
will
biotransform
by
both
methylating
and
demethylating.
Since
environmental
conditions
are
variable,
it
is
difficult
to
quantify
organic
versus
inorganic
arsenic
residues
present
at
any
specific
point
in
time.
Additionally,
it
is
known
that
background
residues
of
both
inorganic
and
organic
arsenics
exist
in
soils,
and
plants,
and
water,
and
vary
greatly
across
the
United
States.
The
assessment
of
the
potential
contribution
to
human
health
risk
from
the
herbicidal
use
of
the
organic
arsenicals
is
further
complicated
by
the
differing
toxicity
profiles
of
the
organic
arsenic
species
(
MMA
differs
from
DMA),
which
both
differ
from
iAs.
In
other
words,
the
target
organs
and
toxicological
effects
are
dissimilar,
as
well
as
the
magnitude
of
the
toxicity.
Hence,
HED
has
chosen
a
stepwise
approach
to
assessing
the
potential
risks
incurred
from
the
use
of
the
organic
arsenicals.
Page
7
of
125
As
part
of
this
stepwise
approach,
assumptions
were
made,
based
on
the
magnitude
of
toxicity,
as
well
as
the
potential
for
biotransformation
to
certain
arsenic
species,
that
were
conservative
and
health
protective.
The
biotransformation
of
the
arsenic
species,
iAs
 
MMA
 
DMA
is
predominantly
unidirectional
in
mammals
and
in
the
environment
but,
environmental
conditions
can
alter
the
progression
from
most
toxic
(
iAs)
to
least
toxic
(
MMA).
It
should
be
noted
that
any
discussion
of
relative
toxicity
(
least
vs.
most)
concerns
the
magnitude
of
the
dose
response,
not
target
organs.
In
vivo
and
in
vitro
toxicity
studies
indicate
that
the
various
arsenical
compounds
have
distinct
toxicological
profiles.
Whereas,
exposure
to
high
levels
of
iAs
in
drinking
water
results
in
a
variety
of
adverse
health
effects
including
diabetes
mellitus,
cardiovascular
disease,
renal
disease,
vascular
skin
lesions
and
cancer,
and
lung,
liver
and
bladder
cancer;
long­
term
animal
studies
with
MMA
suggest
that
the
large
intestine
is
the
target
organ
with
no
neoplastic
lesions
observed
at
any
site.
DMA
causes
bladder
tumors
in
rats
after
feeding
or
drinking
water
exposures.
Because
of
the
distinct
pharmacokinetic
and
pharmacodynamic
differences
that
are
observed
following
direct
oral
exposure
to
MMA
and
DMA,
it
was
appropriate
to
use
chemicalspecific
data
for
extrapolating
risks
for
these
herbicides.
A
more
detailed
discussion
of
these
differences
can
be
found
in
Section
4.0.
The
toxicity
of
iAs
has
been
the
subject
of
risk
assessments
conducted
by
OPP's
Antimicrobial
Division
and
the
Agency's
Office
of
Water
(
OW).
An
in­
depth
discussion
of
iAs
toxicity
can
be
found
in
Chen
2001
and
www.
epa.
gov/
safewater/
arsenic.
html.

Dietary
risk
estimates
were
assumed
to
be
to
residues
resulting
from
the
herbicidal
uses,
with
and
without
background
exposures.
Submitted
plant
and
animal
metabolism
data,
as
well
as
open
literature
show
a
tendency
for
the
organic
arsenicals
to
biotransform
but,
the
extent
and
rapidity
to
which
the
transformation
occurs
at
any
one
time
is
unknown,
so
exposures
are
likely
to
be
to
a
variable
mixture
of
both
organic
and
inorganic
arsenicals.
Currently,
little
is
known
about
the
transformation
of
arsenicals
taken
up
from
the
soil.
For
risk
assessment
purposes
HED
has
provided
a
range
of
risk
estimates
that
assume
no
transformation
of
the
applied
compound,
and
complete
or
partial
transformation
to
DMA.
Potential
risks
from
exposure
to
iAs
were
also
considered.
Dietary
residues
in
food
were
calculated
from
submitted
field
trial
data.
For
potential
co­
occurring
exposures
in
the
diet
from
applications
of
MMA
and
DMA
on
the
same
crop,
1%
co­
occurrence
was
used
and,
as
above,
all
exposures
were
assumed
to
be
to
MMA
and
then,
to
DMA.
Drinking
water
estimates
were
modeled
on
cotton
and
turf
uses
and
occupational
and
residential
exposure
estimates
were
based
on
non­
chemical
specific
monitoring
data
and
standard
operating
procedures
(
SOP).

Modeling
of
the
application
of
arsenical
herbicides
was
performed
by
EFED
to
predict
acute
and
chronic
concentrations
that
may
reach
drinking
water.
Although
there
are
extensive
monitoring
data
available
for
arsenic,
some
of
it
even
targeted
to
heavy
use
areas,
modeling
remains
a
valuable
tool
to
supplement
the
limitations
of
monitoring.
Most
monitoring
measures
total
arsenic
and
does
not
provide
information
on
speciation
or
the
source
of
contamination.
This
is
particularly
important
for
arsenic,
which
has
multiple
potential
sources,
both
from
natural
background
and
from
various
anthropogenic
activities.
The
Estimated
Drinking
Water
Concentrations
(
EDWCs)
are
based
on
maximum
labeled
application
rates
under
the
most
vulnerable
circumstances.
Sorption
of
arsenicals
varies
with
soil
characteristics,
which
in
turn
affects
migration
through
soil
to
sources
of
drinking
water.
Page
8
of
125
Several
acute
and
chronic
dietary
assessments
were
performed
for
the
organic
arsenicals
using
field
trial
data,
Food
and
Drug
Administration
(
FDA)
Total
Diet
Study
(
TDS)
data,
percent
crop
treated
information,
and
default
processing
factors.
Since
arsenic
is
ubiquitous
in
the
environment
and
is
usually
tested
for
as
total
arsenic,
it
is
impossible
at
this
time
to
differentiate
where
the
arsenic
originated
from
(
i.
e.,
background
or
from
herbicidal
use)
or
to
determine
speciated
residue
values
for
use
in
a
national
dietary
exposure
assessment;
therefore,
these
assessments
contain
some
assumptions
that
are
not
standard
for
dietary
exposure
assessments.
A
number
of
the
assumptions
that
have
been
made
in
these
assessments
are
considered
to
be
conservative;
however,
even
when
assuming
that
all
arsenic
found
in
the
field
trials,
reported
in
the
FDA
TDS,
and
estimated
in
drinking
water
is
either
MMA
or
DMA,
risks
are
below
HED's
level
of
concern
[<
100%
Population
Adjusted
Dose
(
PAD)]
for
the
U.
S.
general
population
and
all
population
subgroups
(
highest
89%
aPAD).
Commodities
that
contributed
the
most
to
the
dietary
risk
estimates
are
fish,
water,
rice,
and
cereal
grains.
As
discussed
above,
though
it
is
likely
that
dietary
exposures
are
a
mix
of
arsenic
species,
since
the
toxicity
profiles
of
MMA,
DMA,
and
iAs
differ,
HED
can
only
provide
a
range
of
possibilities
by
showing
potential
risks
from
total
MMA
exposure
and
total
DMA
exposure.
Possible
risks
from
iAs
exposure
are
discussed
later.

There
is
a
potential
for
exposure
in
residential
settings
during
the
application
process
for
homeowners
who
use
products
containing
DMA,
CAMA,
DSMA,
or
MSMA.
HED
uses
the
term
"
handlers"
to
describe
those
individuals
who
are
involved
in
the
pesticide/
herbicide
application
process.
There
is
also
a
potential
for
exposure
from
entering
DMA,
CAMA,
DSMA,
or
MSMA­
treated
areas,
such
as
lawns
and
golf
courses.
HED
uses
the
term
"
postapplication"
to
describe
exposures
to
individuals
that
occur
as
a
result
of
being
in
an
environment
that
has
been
previously
treated
with
a
pesticide.
Cacodylic
acid,
CAMA,
and
MSMA/
DSMA
can
be
used
in
many
areas
that
can
be
frequented
by
the
general
population
including
residential
areas
(
e.
g.,
home
lawns
and
gardens).
As
a
result,
individuals
can
be
exposed
by
entering
these
areas,
if
they
have
been
previously
treated.
Risk
assessments
have
been
completed
for
both
residential
handler
and
postapplication
scenarios.

All
risks
(
i.
e.,
MOEs)
associated
with
the
residential
handler
scenarios
are
not
of
concern;
all
Margins
of
Exposure
(
MOEs)
were
>
100
for
DMA,
CAMA,
MSMA,
and
DSMA.

HED
considered
a
number
of
exposure
scenarios
for
products
that
can
be
used
in
the
residential
environment
representing
different
segments
of
the
population
including
toddlers,
youth­
aged
children,
and
adults.
Short­
term
(
1­
30
days)
MOEs
were
calculated
for
all
scenarios.
In
residential
settings,
HED
does
not
use
restricted­
entry
intervals
or
other
mitigation
approaches
to
limit
postapplication
exposures,
because
they
are
viewed
as
impractical
and
not
enforceable.
As
such,
risk
estimates
on
the
day
of
application
are
the
key
concern.
In
the
assessment
for
residential
postapplication
exposure
and
risk,
there
are
risks
of
concern
for
DMA,
as
they
are
currently
used
in
a
residential
environment.
In
the
assessment
for
residential
postapplication
exposure
and
risk,
there
are
risks
of
concern
for
DMA,
as
they
are
currently
used
in
a
residential
environment.
The
endpoint
used
to
assess
these
incidental
oral
exposures
(
BMDL10)
comes
from
data
measured
at
10
weeks
of
DMA
exposure
in
the
feed
to
female
rats
(
Arnold
et
al,
1999).
However,
Cohen
et
al,
(
2001)
shows
that
regenerative
proliferation
occurred
as
early
as
1
week
into
the
DMA
exposure.
HED
believes
that
using
the
Arnold
(
1999)
study
(
with
the
Cohen
2001
Page
9
of
125
study
as
characterization)
in
conjunction
with
Day
0
DMA
residues
(
calculated
from
the
labeled
application
rates),
constitutes
the
use
of
the
best
available
data
and
that
the
results
can
be
considered
conservative
for
risk
assessment
purposes.

For
the
dermal
and
inhalation,
short­
and
intermediate­
term
exposure,
the
level
of
concern
(
LOC)
or
target
MOE
is
100.
Estimated
risks
above
100
are
not
of
concern.
The
calculated
dermal
and
inhalation
risks
were
not
combined
for
short­
or
intermediate­
term
exposures
because
the
dermal
and
inhalation
endpoints
are
based
on
different
toxicological
effects.
There
are
no
occupational
handler
scenarios
for
MMA
or
DMA
that
have
risks
of
concern,
with
some
level
of
mitigation.

HED
has
determined
that
there
are
potential
exposures
to
postapplication
occupational
workers
during
usual
use­
patterns
associated
with
DMA.
For
lawn
applications
using
DMA,
the
calculated
MOE
ranges
from
22
to
47
on
day
0
(
12
hours
following
application),
and
the
target
MOE
is
not
reached
until
a
week
to
two
weeks
after
application
(
depending
on
the
postapplication
activity).
All
other
postapplication
scenarios
(
for
CAMA,
DSMA,
MSMA,
and
DMA)
have
risks
below
HED's
level
of
concern
on
day
0
(
12
hours
following
application).

Though
potential
aggregate
dietary
(
food
and
water)
risks
that
include
exposures
from
registered
uses
and
background
are
not
of
concern,
whether
exposure
is
assumed
to
be
to
MMA
or
DMA,
residential
postapplication
exposures
to
toddlers
(
from
DMA
and
CAMA)
do
present
potential
risks
of
concern.
Additional
exposures
to
toddlers
through
the
diet
would
increase
these
concerns.

The
Federal
Government
and
most
states
have
established
limits
and/
or
screening
levels
for
"
total
arsenic"
(
unspeciated)
exposure
from
a
variety
of
sources;
drinking
water,
air,
and
soil.
Typically
in
monitoring
programs,
arsenic
is
measured
and
reported
as
total
arsenic,
regardless
of
what
species
(
DMA,
MMA,
iAs),
or
mixture
of
species,
may
be
present,
or
what
the
source
is.
These
limits
or
screening
levels
are
established
based
on
risks
(
cancer)
from
exposure
to
iAs
and
technically
feasible
clean­
up
levels.
Under
FQPA,
the
Agency
is
required
to
consider
all
potential
sources
of
exposure
to
the
organic
arsenicals,
and
their
metabolites
and/
or
transformation
products.
Since
there
is
potential
for
transformation
and
exposure
to
iAs
from
the
registered
uses
of
the
organic
arsenicals,
the
potential
for
risks
from
exposure
to
iAs
was
determined,
which
included
a
comparison
of
estimated
exposures
from
registered
uses
to
existing
regulatory
limits
or
screening
levels
(
see
Section
7.7).

Based
on
the
MMA
and
DMA
dietary
(
food
and
water)
exposure
assessments,
HED
has
determined
that
only
a
small
amount
of
the
total
exposure
needs
to
be
from
iAs
to
reach
HED's
LOC
for
cancer
(
1x10­
6).
The
Agency's
Office
of
Water
has
established
a
Maximum
Concentration
Level
(
MCL)
for
total
arsenic
of
10
ppb.
EDWCs
for
exposure
to
iAs
alone
may
possibly
exceed
the
MCL.
Since
the
MCL
was
established
for
total
arsenic,
exposures
to
any
of
the
arsenic
species
in
water
are
potentially
subject
to
regulation.

HED
considered
the
possible
in­
soil
conversion
of
MMA
and
DMA
to
iAs
to
assess
risks
from
postapplication
dermal
exposures
to
the
soil
and
from
postapplication
incidental
oral
exposures
to
toddlers
ingesting
soil.
EPA's
Office
of
Solid
Waste
and
Emergency
Response's
(
OSWER)
established
a
soil
screening
level
(
SSL)
of
0.4
ppm
for
total
arsenic
(
unspeciated).
Using
very
Page
10
of
125
conservative
assumptions
that
include
100%
conversion
to
iAs
and
100%
bioavailability,
the
arsenic
levels
in
soil
exceeded
the
0.4
ppm
SSL
for
total
arsenic
in
all
cases,
after
one
application.
HED
believes
the
possibility
of
exceeding
the
arsenic
SSL
would
increase
with
the
number
of
arsenic
applications
as
arsenic
in
its
inorganic
form
does
not
degrade
and
evidence
indicates
that
it
may
build
up
in
soil
overtime
as
applications
are
repeated.

2.0
Ingredient
Profile
2.1
Summary
of
Registered
Uses
A
master
label
was
provided
for
all
the
chemicals
by
the
MAA
Task
Force
and
the
uses
and
rates
from
this
master
label
were
used
in
the
assessment.
Note
that
much
higher
rates
are
found
on
some
current
end­
use
product
labels
and
these
higher
rates
will
need
to
be
reduced
to
the
levels
on
the
master
label.

Table
2.1a:
Maximum
Application
Rates
obtained
from
the
Master
Label
for
Cacodylic
Acid
Application
Master
Label
Maximum
Application
Rate
(
lb
ai/
A)
Applications
Per
Year
Cotton
Preconditioning
for
defoliation
0.3
1
Cotton
defoliation
0.8
1
Cotton
defoliation
0.6
2
Lawns
and
Ornamental
Turf
Lawn
renovation
7.3
2
Lawn
edging
7.72
4
Ornamentals
Ornamentals
7.3
6
Non­
Crop
Areas
Non­
crop
7.3
6
Nonbearing
Citrus
Ground
directed
4.96
3
Page
11
of
125
Table
2.1b:
Maximum
Application
Rates
obtained
from
the
Master
Label
for
CAMA
Timing
of
Application/
Use
Site
Master
Label
Maximum
Application
Rate
(
lb
ai/
A)
MMA
equivalent
(
lb
ai/
A)
Applications
Per
Year
Turfgrass
B
Lawns
and
Ornamental
Turf
&
Turf
Grown
for
Sod
By
Ground
only
on
athletic
fields,
golf
courses,
parks
On
Bentgrass:
2.5
2.2
2
By
Ground
on
well
established
actively
growing
turf
On
grasses
other
than
Bent:
5
4.4
2
By
ground
on
established
Bermuda
grass
&
zoysiagrass
4.182
3.6
4
Note:
One
broadcast
application
per
year.
All
additional
applications
are
to
be
spot
treatment
only.
In
Florida
all
applications
 
spot
treatment
only.

Table
2.1c:
Maximum
Application
Rates
obtained
from
the
Master
Label
for
DSMA
Timing
of
Application
Master
Label
Maximum
Application
Rate
(
lb
ai/
A)
MMA
equivalent
(
lb
ai/
A)
Maximum
Number
of
Applications
Per
Crop
Cotton
By
ground
or
air:
pre­
plant
or
post­
plant
(
up
to
cracking)
2.268
1.7
1
By
ground
or
air:
post­
emergent
(
as
over
the
top
broadcast
spray)
2.268
1.7
1
By
ground:
post­
emergent
(
directed
spray
application)
2.268
1.7
2
By
ground:
post­
emergent
(
directed
band
application)­
based
on
40
inch
row
spacing)
2.268
1.7
2
Grasses
Grown
for
Seed
in
Pacific
Northwest
only
(
Ryegrass,
Fescue,
and
Bluegrass)
Pacific
Northwest
apply
before
boot
stage
4.4
3.3
1
Lawns,
Ornamental
Turf,
and
Sod
Farms
By
Ground
on
well
established
actively
growing
turf
3.293
2.5
4
Sod
Farms
3.293
2.5
4
Nonbearing
Orchards
and
Vineyards
Ground
directed
4.85
3.7
3
Noncrop
Areas
Ground
application
5.1
3.9
4
Page
12
of
125
Table
2.1d:
Maximum
Application
Rates
obtained
from
the
Master
Label
for
MSMA
Timing
of
Application
Master
Label
Maximum
Application
Rate
(
lb
ai/
A)
MMA
equivalent
(
lb
ai/
A)
Maximum
Number
of
Applications
Per
Crop
Cotton
By
ground
or
air:
pre­
plant
or
post­
plant
(
up
to
cracking)
2.0
1.7
1
1.875
1.6
1
By
ground
or
air:
post­
emergent
(
as
over
the
top
broadcast
spray)
0.9375
0.8
2
By
ground:
post­
emergent
(
directed
spray
application)
2.0
1.7
2
Grasses
Grown
for
Seed
in
Pacific
Northwest
only
(
Ryegrass,
Fescue,
and
Bluegrass)

Pacific
Northwest
apply
before
boot
stage
6.16
5.3
1
Lawns,
Ornamental
Turf,
and
Sod
Farms
By
Ground
only
on
athletic
fields,
golf
courses,
parks
2.6136
2.3
4
By
Ground
on
well
established
actively
growing
turf
2.178
1.9
4
By
ground
on
established
Bermuda
grass
&
zoysiagrass
3.9204
3.4
4
Sod
Farms
3.9204
3.4
4
Nonbearing
Orchards
and
Vineyards
Ground
directed
4
3.5
3
Noncrop
Areas
Ground
application
4.5
3.9
4
Page
13
of
125
2.2
Structure
and
Nomenclature
TABLE
2.2:
Test
Compound
Nomenclature
Cacodylic
Acid
&
Sodium
Cacodylate
Chemical
structure
Cacodylic
Acid
Sodium
Cacodylate
Empirical
formula
C2
H7
AsO2
/
C2
H6
AsNaO2
Common
name
Cacodylic
Acid/
Sodium
Cacodylate
Other
names
dimethylarsinic
acid,
dimethyl
arsonate,
DMA
Molecular
Weight
137.99
/
159.99
PC
Code
012501
/
012502
CAS
Registry
Number
75­
60­
5
/
124­
65­
2
Chemical
Class
Organic
Arsenic
Known
Impurities
of
Concern
Unknown
MSMA/
DSMA/
CAMA
Chemical
structure
MSMA
DSMA
CAMA
Empirical
formula
CH4
AsNaO3
/
CH3
AsNa2O3
/
(
CH4
AsO3
)
2
Ca
Common
name
MSMA/
DSMA/
CAMA
Other
names
monosodium
methanearsonate
(
MSMA);
disodium
methanearsonate
(
DSMA),
calcium
acid
methanearsonate
(
CAMA),
methylarsinic
acid,
MAA
monomethyl
arsonate,
MMA
Molecular
Weight
161.94
/
183.92
/
318
PC
Code
013803
/
013802
/
013806
CAS
Registry
Number
2163­
80­
6
/
144­
21­
8
/
5902­
95­
4
Chemical
Class
Organic
Arsenic
Known
Impurities
of
Concern
Unknown
As
O
C
H
3
OH
CH
3
As
O
C
H
3
O
CH
3
Na
+

As
OH
O
O
C
H
3
Na
+

As
O
O
O
C
H
3
Na
+
Na
+

As
O
C
H
3
O
OH
2
Ca
2+
Page
14
of
125
2.3
Physical
and
Chemical
Properties
Table
2.3a:
Product
Chemistry
Data
Summary
for
Cacodylic
Acid
OPPTS
Guideline
Numbers
Data
Requirements:
Cacodylic
Acid
[
TGAI]
PC
Code
012501
CAS#
75­
60­
5
Master
Record
Identification
[
MRID#]
or
Reference
Are
Data
Requirements
Fulfilled?
Results
or
*
Data
Gap
830.1550
Product
Identity
and
Composition
NO
*
DATA
GAP
830.1600
Description
of
Materials
Used
to
Produce
the
Product
NO
*
DATA
GAP
830.1620
Description
of
Production
Process
NO
*
DATA
GAP
830.1650
Description
of
Formulation
Process
NO
*
DATA
GAP
830.1670
Discussion
of
Formation
of
Impurities
NO
*
DATA
GAP
830.1700
Preliminary
Analysis
41608302,
42614501
YES
830.1750
Certified
Limits
NO
*
DATA
GAP
830.1800
Enforcement
Analytical
Method
NO
*
DATA
GAP
830.1900
Submittal
of
Samples
NO
*
DATA
GAP
830.6302
Color
40957813
42473801
YES
WHITE
830.6303
Physical
State
40957813
42473801
YES
CRYSTALLINE
SOLID
830.6304
Odor
40957813,
42473801
YES
NO
ODOR
830.6313
Stability
to
normal
and
elevated
temperatures,
metals
and
metal
ions
NO
*
DATA
GAP
830.7000
pH
40957813,
42473801
YES
830.7050
UV/
VIS
absorption
NO
*
DATA
GAP
830.7200
Melting
Point/
Melting
Range
42397101
YES
192
º
C
 
194
º
C
830.7220
Boiling
Point/
Boiling
Point
Range
NOT
APPLICABLE
SEE
GUIDELINE
830.7220
830.7300
Density/
Relative
Density/
Bulk
Density
40957813
42473801
YES
1.10
g
/
mL
830.7370
Dissociation
Constant
42403501
YES
6.17
AT
25
º
C
830.7550
Partition
coefficient
(
n­
octanol
/
water)
shake
flask
method
42397101
YES
K
O/
W
=
<
0.028
AT
25
º
C
830.7560
Partition
coefficient
(
n­
octanol
/
water)
generator
column
method
SEE
GUIDELINE
830.7550
830.7570
Partition
coefficient
(
n­
octanol
/
water)
estimation
by
liquid
chromatography
SEE
GUIDELINE
830.7550
830.7840
Water
Solubility:
Column
Elution
Method;
Shake
Flask
Method
42397101
YES
102
g
/
100mL
830.7860
Water
solubility
generator
column
method
SEE
GUIDELINE
830.7840
830.7950
Vapor
pressure
NO
*
DATA
GAP
Page
15
of
125
Table
2.3b:
Product
Chemistry
Data
Summary
for
Sodium
Cacodylate
OPPTS
Guideline
Numbers
Data
Requirements
Sodium
Cacodylate
[
TGAI]
PC
Code
012502
CAS#
124­
65­
2
Master
Record
Identification
[
MRID#]
or
Reference
Are
Data
Requirements
Fulfilled?
Results
or
*
Data
Gap
830.1550
Product
Identity
and
Composition
NO
*
DATA
GAP
830.1600
Description
of
Materials
Used
to
Produce
the
Product
NO
*
DATA
GAP
830.1620
Description
of
Production
Process
NO
*
DATA
GAP
830.1650
Description
of
Formulation
Process
NO
*
DATA
GAP
830.1670
Discussion
of
Formation
of
Impurities
NO
*
DATA
GAP
830.1700
Preliminary
Analysis
41608302,
42614501
YES
830.1750
Certified
Limits
NO
*
DATA
GAP
830.1800
Enforcement
Analytical
Method
NO
*
DATA
GAP
830.1900
Submittal
of
Samples
NO
*
DATA
GAP
830.6302
Color
40957813
42473801
YES
WHITE
830.6303
Physical
State
40957813
42473801
YES
CRYSTALLINE
SOLID
830.6304
Odor
40957813,
42473801
YES
NO
ODOR
830.6313
Stability
to
normal
and
elevated
temperatures,
metals
and
metal
ions
42403501
YES
STABLE
830.7000
pH
42473801
YES
830.7050
UV/
VIS
absorption
NO
*
DATA
GAP
830.7200
Melting
Point/
Melting
Range
42403501
YES
77
oC
 
79.5
oC
830.7220
Boiling
Point/
Boiling
Point
Range
NOT
APPLICABLE
830.7300
Density/
Relative
Density/
Bulk
Density
40957813
42473801
YES
1.10
g
/
mL
830.7370
Dissociation
Constant
42403501
YES
6.21
at
25
oC
830.7550
Partition
coefficient
(
n­
octanol
/
water)
shake
flask
method
NOT
APPLICABLE
CRBS
8865,
D170691
12/
12/
1991
A.
Perfetti
830.7560
Partition
coefficient
(
n­
octanol
/
water)
generator
column
method
830.7570
Partition
coefficient
(
n­
octanol
/
water)
estimation
by
liquid
chromatography
SEE
GUIDELINE
830.7550
830.7840
Water
Solubility:
Column
Elution
Method;
Shake
Flask
Method
42397101
YES
82
g
/
100
mL
830.7860
Water
solubility
generator
column
method
SEE
GUIDELINE
830.7840
830.7950
Vapor
pressure
NO
*
DATA
GAP
Page
16
of
125
Table
2.3c:
Product
Chemistry
Data
Summary
for
DiSodium
Methanearsonic
salt
OPPTS
Guideline
Numbers
Luxembourg­
Pamol,
Inc.
Data
Requirements:
DSMA
[
TGAI]
PC
Code
013802
CAS#
144­
21­
8
Master
Record
Identification
[
MRID#]
Are
Data
Requirements
Fulfilled?
Results
or
*
Deficiency
830.1550
Product
Identity
and
Composition
NO
*
Data
Gap
830.1600
Description
of
Materials
Used
to
Produce
the
Product
42388301,
44150401
YES
830.1620
Description
of
Production
Process
42388301,
44150401
YES
830.1650
Description
of
Formulation
Process
NO
*
Data
Gap
830.1670
Discussion
of
Formation
of
Impurities
NO
*
Data
Gap
830.1700
Preliminary
Analysis
42053701,
45053702
YES
830.1750
Certified
Limits
NO
*
Data
Gap
830.1800
Enforcement
Analytical
Method
NO
*
Data
Gap
830.1900
Submittal
of
Samples
NO
*
Data
Gap
830.6302
Color
42451102
YES
WHITE
830.6303
Physical
State
42451102
YES
CRYSTALINE
SOLID
830.6304
Odor
42451102
YES
No
Odor
830.6313
Stability
to
normal
and
elevated
temperatures,
metals
and
metal
ions
NO
*
Data
Gap
830.7000
pH
41982002
YES
830.7050
UV/
VIS
absorption
NO
*
Data
Gap
830.7200
Melting
Point/
Melting
Range
41982001
YES
>
300
º
C
830.7220
Boiling
Point/
Boiling
Point
Range
NOT
APPLICABLE
830.7300
Density/
Relative
Density/
Bulk
Density
42451102
YES
830.7370
Dissociation
Constant
41976201
YES
830.7550
Partition
coefficient
(
n­
octanol
/
water)
shake
flask
method
41976202
YES
Log
P
O/
W
<
1
830.7560
Partition
coefficient
(
n­
octanol
/
water)
generator
column
method
SEE
GUIDELINE
830.7550
830.7570
Partition
coefficient
(
n­
octanol
/
water)
estimation
by
liquid
chromatography
SEE
GUIDELINE
830.7550
830.7840
Water
Solubility:
Column
Elution
Method;
Shake
Flask
Method
41602502
YES
830.7860
Water
solubility,
generator
column
method
SEE
GUIDELINE
830.7840
830.7950
Vapor
pressure
42120701
YES
0.0000001
mm
Hg
at
25
°
C
Page
17
of
125
Table
2.3d:
Product
Chemistry
Data
Summary
for
DiSodium
Methanearsonic
salt
OPPTS
Guideline
Numbers
APC
Holdings
Data
Requirements:
DSMA
[
TGAI]
PC
Code
013802
CAS#
144­
21­
8
Master
Record
Identification
[
MRID#]
Are
Data
Requirements
Fulfilled?
Results
or
*
Deficiency
830.1550
Product
Identity
and
Composition
NO
*
DATA
GAP
830.1600
Description
of
Materials
Used
to
Produce
the
Product
42361001
YES
830.1620
Description
of
Production
Process
42361001
YES
830.1650
Description
of
Formulation
Process
NO
*
DATA
GAP
830.1670
Discussion
of
Formation
of
Impurities
42053701
YES
830.1700
Preliminary
Analysis
42053702
YES
830.1750
Certified
Limits
NO
*
DATA
GAP
830.1800
Enforcement
Analytical
Method
NO
*
DATA
GAP
830.1900
Submittal
of
Samples
NO
*
DATA
GAP
830.6302
Color
42451102
YES
830.6303
Physical
State
42451102
YES
830.6304
Odor
42451102
YES
NO
ODOR
830.6313
Stability
to
normal
and
elevated
temperatures,
metals
and
metal
ions
NO
*
DATA
GAP
830.7000
pH
41982002
YES
830.7050
UV/
VIS
absorption
NO
*
DATA
GAP
830.7200
Melting
Point/
Melting
Range
41982001
YES
830.7220
Boiling
Point/
Boiling
Point
Range
SEE
GUIDELINE
830.7200
830.7300
Density/
Relative
Density/
Bulk
Density
42451102
YES
830.7370
Dissociation
Constant
41976201
YES
830.7550
Partition
coefficient
(
n­
octanol
/
water)
shake
flask
method
41976202
YES
830.7560
Partition
coefficient
(
n­
octanol
/
water)
generator
column
method
830.7570
Partition
coefficient
(
n­
octanol
/
water)
estimation
by
liquid
chromatography
SEE
GUIDELINE
830.7550
830.7840
Water
Solubility:
Column
Elution
Method;
Shake
Flask
Method
41602502
YES
830.7860
Water
solubility,
generator
column
method
SEE
GUIDELINE
830.7840
830.7950
Vapor
pressure
42120701
YES
Page
18
of
125
Table
2.3e:
Product
Chemistry
Data
Summary
for
DiSodium
Methanearsonic
salt
OPPTS
Guideline
Numbers
GB
Biosciences
Corporation
Data
Requirements:
81%
DSMA
FI
[
Technical]
PC
Code
013802
CAS#
144­
21­
8
Master
Record
Identification
[
MRID#]
Are
Data
Requirements
Fulfilled?
Results
or
*
Deficiency
830.1550
Product
Identity
and
Composition
42051902
YES
CSF
09/
23/
1991
830.1600
Description
of
Materials
Used
to
Produce
the
Product
NO
*
DATA
GAP
830.1620
Description
of
Production
Process
NO
*
DATA
GAP
830.1650
Description
of
Formulation
Process
NO
*
DATA
GAP
830.1670
Discussion
of
Formation
of
Impurities
NO
*
DATA
GAP
830.1700
Preliminary
Analysis
NO
*
DATA
GAP
830.1750
Certified
Limits
42051902,
CSF
09/
23/
1991
YES
830.1800
Enforcement
Analytical
Method
NO
*
DATA
GAP
830.1900
Submittal
of
Samples
NO
*
DATA
GAP
830.6302
Color
NO
*
DATA
GAP
830.6303
Physical
State
NO
*
DATA
GAP
830.6304
Odor
NO
*
DATA
GAP
830.6313
Stability
to
normal
and
elevated
temperatures,
metals
and
metal
ions
NO
*
DATA
GAP
830.7000
pH
NO
*
DATA
GAP
830.7050
UV/
VIS
absorption
NO
*
DATA
GAP
830.7200
Melting
Point/
Melting
Range
NO
*
DATA
GAP
830.7220
Boiling
Point/
Boiling
Point
Range
NO
*
DATA
GAP
830.7300
Density/
Relative
Density/
Bulk
Density
NO
*
DATA
GAP
830.7370
Dissociation
Constant
NO
*
DATA
GAP
830.7550
Partition
coefficient
(
n­
octanol
/
water)
shake
flask
method
NO
*
DATA
GAP
830.7560
Partition
coefficient
(
n­
octanol
/
water)
generator
column
method
NO
*
DATA
GAP
830.7570
Partition
coefficient
(
n­
octanol
/
water)
estimation
by
liquid
chromatography
NO
*
DATA
GAP
830.7840
Water
Solubility:
Column
Elution
Method;
Shake
Flask
Method
NO
*
DATA
GAP
830.7860
Water
solubility,
generator
column
method
NO
*
DATA
GAP
830.7950
Vapor
pressure
NO
*
DATA
GAP
Page
19
of
125
Table
2.3f:
Product
Chemistry
Data
Summary
for
MonoSodium
Methanearsonic
salt
OPPTS
Guideline
Numbers
Luxembourg­
Pamol,
Inc
Data
Requirements:
MSMA
[
TGAI]
PC
Code
013803
CAS#
2163­
80­
6
Master
Record
Identification
[
MRID#]
Are
Data
Requirements
Fulfilled?
Results
or
*
Deficiency
830.1550
Product
Identity
and
Composition
NO
*
DATA
GAP
830.1600
Description
of
Materials
Used
to
Produce
the
Product
NO
*
DATA
GAP
830.1620
Description
of
Production
Process
41602701,
42387801
YES
830.1650
Description
of
Formulation
Process
NO
*
DATA
GAP
830.1670
Discussion
of
Formation
of
Impurities
41602701,
42387801
YES
830.1700
Preliminary
Analysis
42387802
YES
830.1750
Certified
Limits
NO
*
DATA
GAP
830.1800
Enforcement
Analytical
Method
NO
*
DATA
GAP
830.1900
Submittal
of
Samples
NO
*
DATA
GAP
830.6302
Color
41610001,
42451101
YES
WHITE
830.6303
Physical
State
41610001,
42451101
YES
CRYSTALLINE
830.6304
Odor
41610001,
42451101
YES
NO
ODOR
830.6313
Stability
to
normal
and
elevated
temperatures,
metals
and
metal
ions
41610001,
42378601
YES
830.7000
pH
41610001,
42378601
YES
830.7050
UV/
VIS
absorption
NO
*
DATA
GAP
830.7200
Melting
Point/
Melting
Range
41789501
YES
830.7220
Boiling
Point/
Boiling
Point
Range
NOT
APPLICABLE
830.7300
Density/
Relative
Density/
Bulk
Density
42451101
YES
1.65
g/
mL
at
25
º
C
830.7370
Dissociation
Constant
41610001
YES
830.7550
Partition
coefficient
(
n­
octanol
/
water)
shake
flask
method
830.7560
Partition
coefficient
(
n­
octanol
/
water)
generator
column
method
830.7570
Partition
coefficient
(
n­
octanol
/
water)
estimation
by
liquid
chromatography
NO
*
DATA
GAP
830.7840
Water
Solubility:
Column
Elution
Method;
Shake
Flask
Method
41610001
YES
830.7860
Water
solubility,
generator
column
method
SEE
GUIDELINE
830.7840
830.7950
Vapor
pressure
41610001,
41651901
YES
0.00001
Pa
Page
20
of
125
Table
2.3g:
Product
Chemistry
Data
Summary
for
MonoSodium
Methanearsonic
salt
OPPTS
Guideline
Numbers
APC
Holdings,
Inc.
Data
Requirements:
MSMA
[
TGAI]
PC
Code
013803
CAS#
2163­
80­
6
Master
Record
Identification
[
MRID#]
Are
Data
Requirements
Fulfilled?
Results
or
*
Deficiency
830.1550
Product
Identity
and
Composition
NO
*
DATA
GAP
830.1600
Description
of
Materials
Used
to
Produce
the
Product
41702001
YES
830.1620
Description
of
Production
Process
41702001
YES
830.1650
Description
of
Formulation
Process
NO
*
DATA
GAP
830.1670
Discussion
of
Formation
of
Impurities
42474101
YES
830.1700
Preliminary
Analysis
41702002,
42474101
YES
830.1750
Certified
Limits
NO
*
DATA
GAP
830.1800
Enforcement
Analytical
Method
NO
*
DATA
GAP
830.1900
Submittal
of
Samples
NO
*
DATA
GAP
830.6302
Color
41610001
YES
830.6303
Physical
State
41610001
YES
830.6304
Odor
41610001
YES
NO
ODOR
830.6313
Stability
to
normal
and
elevated
temperatures,
metals
and
metal
ions
41610001,
4237801
YES
830.7000
pH
41610001,
4237801
YES
830.7050
UV/
VIS
absorption
NO
*
DATA
GAP
830.7200
Melting
Point/
Melting
Range
41789501
YES
830.7220
Boiling
Point/
Boiling
Point
Range
SEE
GUIDELINE
830.7200
830.7300
Density/
Relative
Density/
Bulk
Density
42451101
YES
830.7370
Dissociation
Constant
41610001
YES
830.7550
Partition
coefficient
(
n­
octanol
/
water)
shake
flask
method
830.7560
Partition
coefficient
(
n­
octanol
/
water)
generator
column
method
830.7570
Partition
coefficient
(
n­
octanol
/
water)
estimation
by
liquid
chromatography
NO
*
DATA
GAP
830.7840
Water
Solubility:
Column
Elution
Method;
Shake
Flask
Method
41610001
YES
830.7860
Water
solubility,
generator
column
method
SEE
GUIDELINE
830.7840
830.7950
Vapor
pressure
41610001,
41651901
YES
Page
21
of
125
Table
2.3h:
Product
Chemistry
Data
Summary
for
MonoSodium
Methanearsonic
salt
OPPTS
Guideline
Numbers
GB
Biosciences
Corporation
Data
Requirements:
MSMA
59%
[
Technical]
PC
Code
013803
CAS#
2163­
80­
6
Master
Record
Identification
[
MRID#]
Are
Data
Requirements
Fulfilled?
Results
or
*
Deficiency
830.1550
Product
Identity
and
Composition
42153501
YES
830.1600
Description
of
Materials
Used
to
Produce
the
Product
42081201
YES
830.1620
Description
of
Production
Process
42081201
YES
830.1650
Description
of
Formulation
Process
NO
*
DATA
GAP
830.1670
Discussion
of
Formation
of
Impurities
41608101
YES
830.1700
Preliminary
Analysis
41608101
YES
830.1750
Certified
Limits
NO
*
DATA
GAP
830.1800
Enforcement
Analytical
Method
NO
*
DATA
GAP
830.1900
Submittal
of
Samples
NO
*
DATA
GAP
830.6302
Color
NO
*
DATA
GAP
830.6303
Physical
State
NO
*
DATA
GAP
830.6304
Odor
NO
*
DATA
GAP
830.6313
Stability
to
normal
and
elevated
temperatures,
metals
and
metal
ions
41610001,
42378601
YES
830.7000
pH
NO
*
DATA
GAP
830.7050
UV/
VIS
absorption
NO
*
DATA
GAP
830.7200
Melting
Point/
Melting
Range
41789501
YES
830.7220
Boiling
Point/
Boiling
Point
Range
SEE
GUIDELINE
830.7200
830.7300
Density/
Relative
Density/
Bulk
Density
NO
*
DATA
GAP
830.7370
Dissociation
Constant
41610001
YES
830.7550
Partition
coefficient
(
n­
octanol
/
water)
shake
flask
method
830.7560
Partition
coefficient
(
n­
octanol
/
water)
generator
column
method
830.7570
Partition
coefficient
(
n­
octanol
/
water)
estimation
by
liquid
chromatography
NO
*
DATA
GAP
830.7840
Water
Solubility:
Column
Elution
Method;
Shake
Flask
Method
41610001
YES
830.7860
Water
solubility,
generator
column
method
SEE
GUIDELINE
830.7840
830.7950
Vapor
pressure
41610001,
41651901
YES
Page
22
of
125
Table
2.3i:
Product
Chemistry
Data
Summary
for
Calcium
Methanearsonate
OPPTS
Guideline
Numbers
APC
Holding
Company
Data
Requirements:
CAMA
[
TGAI]
PC
Code
013806
CAS#
5902­
95­
4
Master
Record
Identification
[
MRID#]
Are
Data
Requirements
Fulfilled?
Results
or
*
Deficiency
830.1550
Product
Identity
and
Composition
NO
*
DATA
GAP
830.1600
Description
of
Materials
Used
to
Produce
the
Product
42913801
YES
830.1620
Description
of
Production
Process
42913801
YES
830.1650
Description
of
Formulation
Process
NO
*
DATA
GAP
830.1670
Discussion
of
Formation
of
Impurities
42913801
YES
830.1700
Preliminary
Analysis
42825901
YES
830.1750
Certified
Limits
NO
*
DATA
GAP
830.1800
Enforcement
Analytical
Method
NO
*
DATA
GAP
830.1900
Submittal
of
Samples
NO
*
DATA
GAP
830.6302
Color
42807602
YES
830.6303
Physical
State
42807603
YES
830.6304
Odor
42807604
YES
830.6313
Stability
to
normal
and
elevated
temperatures,
metals
and
metal
ions
42807609
YES
830.7000
pH
42807608
YES
830.7050
UV/
VIS
absorption
NO
*
DATA
GAP
830.7200
Melting
Point/
Melting
Range
42807605
YES
830.7220
Boiling
Point/
Boiling
Point
Range
SEE
GUIDELINE
830.7200
830.7300
Density/
Relative
Density/
Bulk
Density
42807606
YES
830.7370
Dissociation
Constant
Memo
YES
MEMO
09/
29/
1995,
07/
29/
1993,
A.
SMITH
830.7550
Partition
coefficient
(
n­
octanol
/
water)
shake
flask
method
830.7560
Partition
coefficient
(
n­
octanol
/
water)
generator
column
method
830.7570
Partition
coefficient
(
n­
octanol
/
water)
estimation
by
liquid
chromatography
NO
*
DATA
GAP
830.7840
Water
Solubility:
Column
Elution
Method;
Shake
Flask
Method
42807607
YES
830.7860
Water
solubility,
generator
column
method
SEE
GUIDELINE
830.7840
830.7950
Vapor
pressure
NO
*
DATA
GAP
Page
23
of
125
3.0
Metabolism
Assessment
3.1
Comparative
Metabolic
Profile
Toxicokinetic
factors
(
i.
e.,
absorption,
distribution,
metabolism,
and
excretion)
play
critical
roles
in
the
evaluation
of
quantitative
dose­
response
relationships
since
these
factors
influence
the
amount
of
chemical
at
the
site
of
action,
along
with
the
time
course
for
exposure
at
that
site.
Section
2.
C.
Toxicokinetics
and
Metabolism
of
USEPA,
2005b
provides
details
on
the
available
studies
in
humans
and
animals
which
characterize
the
metabolism
following
administration
of
iAs,
MMAV
or
DMAV.
Although
species
differences
exist,
these
in
vivo
studies
indicate
that
the
methylation/
reduction
of
iAs
to
MMAV
or
DMAV
is
highly
efficient,
particularly
in
rodents
and
humans.
However,
when
MMAV
or
DMAV
are
administered
as
parent
compound,
further
methylation
of
MMAV
or
DMAV
is
less
efficient.
The
results
of
the
in
vivo
studies
are
further
supported
by
the
in
vitro
evidence.
Specifically,
the
in
vitro
evidence
indicates
that
the
cellular
absorption
of
MMAV
or
DMAV
is
less
than
that
of
iAsV,
MMAIII,
or
DMAIII.

The
biomethylation
of
arsenic
involves
alternating
steps
in
which
trivalent
arsenic
is
oxidatively
methylated
and
then
reduced
from
pentavalency
to
trivalency
(
Figure
3.1).
In
mammals,
the
methylation
and
reduction
reactions
are
enzymatically
catalyzed.
Some
research
suggests
that
distinct
methyltransferases
and
reductases
catalyze
each
step
in
the
pathway
that
leads
from
inorganic
arsenic
to
methylated
arsenicals,
while
other
investigators
have
found
orthologous
genes
encoding
arsenic
(+
3
oxidation
state)
methyltransferase
(
AS3MT)
in
the
genomes
of
rat,
mouse,
and
human.
AS3MT
catalyzes
all
steps
in
the
pathway
from
arsenite
to
mono,
di,
and
trimethylated
products.

Less
is
known
about
the
capacity
for
the
reduction
of
pentavalent
methylated
arsenicals
into
trivalent
methylated
arsenicals.
In
assays
containing
AS3MT,
the
low
rates
of
conversion
of
substrates
containing
pentavalent
arsenic
into
the
expected
methylated
products
suggest
that
unknown
factors
limit
the
capacity
of
the
enzyme
to
reduce
the
substrate.
Similarly,
in
cultured
cells,
pentavalent
arsenicals
are
converted
to
methylated
products
at
much
slower
rates
than
are
trivalent
arsenicals.
The
low
rate
of
conversion
could
reflect
inefficient
reduction
of
the
substrate
before
oxidative
methylation
or
could
reflect
the
relatively
slow
uptake
of
pentavalent
arsenicals
into
cells.
.
Page
24
of
125
TMAsIII
TMAsV
Methylation
Reduction
Figure
3.1:
Scheme
for
the
Methylation
of
As
Page
25
of
125
3.1.1
In
vivo
Metabolism
Studies
Humans
and
many
other
mammals
efficiently
methylate
iAs
to
mono­,
di­
and
trimethyl
arsenicals.
The
degree
of
methylation
varies
by
species
(
see
more
detail
in
USEPA
2006).
Some
species
such
as
the
guinea
pig,
marmoset
monkey
and
chimpanzee
do
not
appear
to
methylate
iAs.
When
humans
are
exposed
to
iAs,
urinary
concentrations
of
methylated
metabolites
vary
among
populations.
However,
when
exposed
iAs,
particularly
in
drinking
water,
human
urine
typically
contains
10­
20%
iAs,
10­
20%
MMA,
and
60­
80%
DMA.
Humans
tend
to
excrete
higher
amounts
of
MMAV
(
10­
20%)
than
do
mice
(<
1%)
after
exposure
to
iAs.
Rats
and
hamsters
tend
to
excrete
more
TMAO
than
other
species
following
exposure
to
DMA.
Recent
studies
have
detected
the
trivalent
species
of
MMA
and
DMA
in
human
urine
following
exposure
to
drinking
water
contaminated
with
iAs.
Following
direct
exposure
to
MMAV
and
DMAV,
these
compounds
are
methylated
to
a
lesser
degree
by
laboratory
animals
and
humans
compared
to
that
of
iAsV.

Section
2.
C.
2
of
USEPA
2006
describes
the
in
vivo
metabolism
of
key
arsenical
compounds.
Figures
3.1.1a,
3.1.1b,
and
3.1.1c
summarize
the
results
of
in
vivo
metabolism
studies.
In
summary,
the
available
in
vivo
metabolism
studies
indicate
that:

 
When
exposed
directly
to
iAs,
arsenic
is
efficiently
absorbed
and
methylated
in
human
and
laboratory
animal
tissues.

 
Ingested
MMAV
and
DMAV
are
eliminated
more
rapidly
compared
to
ingested
iAs.

 
Studies
in
laboratory
animals
indicate
little
or
no
demethylation
of
either
MMAV
or
DMAV
(
i.
e.,
production
of
inorganic
arsenic
from
methylated
arsenicals
is
minimal
to
nonexistent).
Page
26
of
125
Figure
3.1.1a
provides
a
visual
representation
of
some
of
the
key
differences
between
humans
and
rats
regarding
exogenous
exposure
to
iAs.
iAs
is
efficiently
methylated
to
MMAV
and/
or
DMAV.

Figure
3.1.1a:
General
metabolic
profile
following
direct
exposure
to
iAs.

iAsV
Limited
cellular
uptake
iAsIII
Extensive
cellular
uptake
iAsIII
MMAV
MMAs
10­
20%
of
Human
urinary
excretion
MMAII
I
DMAV
DMAIII
DMAs
60­
80%
of
Human
urinary
excretion
TMAO
TMAO
None
found
in
human
urine
5­
10%
of
Rat
urinary
excretion
TMA
Page
27
of
125
Figure
3.1.1b
provides
a
visual
representation
of
some
key
differences
between
humans
and
rats
regarding
exogenous
exposure
to
MMAV.
Following
direct
exposure
to
MMAV,
humans
and
rats
excrete
MMAV
predominately
unchanged.
Only
a
portion
of
MMAV
is
methylated
to
DMAV
in
humans
and
rats.
Excretion
of
MMAV
occurs
rapidly
compared
to
excretion
of
arsenic
following
exposure
to
iAs.

Figure
3.1.1b:
General
metabolic
profile
following
direct
exposure
to
MMAV
MMAV
Limited
cellular
uptake
MMAV
MMAs
Excreted
primarily
unchanged
in
human
urine
(>
80%)
MMAIII
DMAV
DMAIII
DMAs
~
12%
of
Human
urinary
excretion
~
20%
of
Rat
urinary
excretion
TMAO
TMAO
None
found
in
human
urine
~
5%
of
Rat
urinary
excretion
TMA
Page
28
of
125
Figure
3.1.1c
provides
a
visual
representation
of
some
key
differences
between
humans
and
rats
regarding
exogenous
exposure
to
DMAV.
Following
direct
exposure
to
DMAV,
humans
excrete
DMAV
predominately
unchanged.
Rats
tend
to
excrete
more
TMAO
than
other
species.
Excretion
of
DMAV
is
more
rapid
than
excretion
of
arsenic
following
exposure
to
iAs
or
MMAV.

Figure
3.1.1c:
General
metabolic
profile
following
direct
exposure
to
DMAV
DMAV
Limited
cellular
uptake
DMAV
DMAs:
Excreted
primarily
unchanged
in
human
urine
(>
95%)
DMAIII
TMA
TMAO
Small
amount
(~
4%)
in
human
urinary
excretion
~
20­
40%
of
rat
urinary
excretion
TMAO
Page
29
of
125
3.1.2
In
vitro
Studies
There
is
evidence
from
in
vitro
studies
which
indicates
that
iAs
is
more
readily
taken
up
by
cells
compared
to
the
cellular
uptake
of
MMAV
and
DMAV.
Because
methylation
occurs
intracellularly,
these
studies
provide
characterization
of
the
biological
processes
leading
to
the
differences
observed
in
the
in
vivo
metabolism
studies.
Furthermore,
the
differential
cellular
uptake
of
iAs,
MMAV,
or
DMAV
also
provides
characterization
of
the
potential
intracellular
exposure
contributing
to
the
differential
toxicological
profiles
of
the
arsenicals.

In
each
of
the
in
vitro
studies
(
described
in
2.
C.
3
of
USEPA
2006),
cellular
uptake
of
iAsIII
and/
or
iAsV
was
shown
to
be
greater
than
cellular
uptake
for
MMAV
and
DMAV.
In
vitro
metabolism
studies
also
suggest
that
reduction
of
iAsV
occurs
at
a
greater
rate
in
vitro
than
reduction
of
DMAV,
and
that
MMAIII
is
readily
methylated
but
MMAV
is
not.
The
in
vivo
metabolism
studies
described
in
USEPA
2006
indicate
that
methylation
is
more
efficient
in
humans,
mice,
hamsters,
and
rats
following
direct
exposure
to
iAs
compared
to
methylation
rates
following
direct
exposure
to
MMAV
and
DMAV.
The
in
vitro
studies
suggest
that,
at
least
in
part,
the
differences
in
in
vivo
methylation
may
be
related
to
the
degree
to
which
arsenical
compounds
are
taken
up
into
the
cell
as
well
as
reduced.

3.2
Nature
of
the
Residue
in
Foods
Based
on
the
available
data
and
published
information
on
cacodylic
acid,
the
Metabolism
Committee
concluded
that
the
only
residue
of
concern
is
cacodylic
acid
(
DMA)
per
se
(
Swartz
1995).
Little
or
no
demethylation
of
cacodylic
acid
is
likely
to
occur
in/
on
cotton
and
animal
commodities.
Submitted
plant
and
animal
metabolism
data
support
this
finding.
However,
there
are
no
available
data
to
show
how
plants
metabolize
residues
taken
up
from
contaminated
soils.
Monitoring
data,
which
measures
total
arsenic
(
unspeciated),
shows
measurable
amounts
of
arsenic
in
foods,
including
meat
and
milk.

3.2.1
Description
of
Primary
Crop
Metabolism
The
qualitative
nature
of
MMA
residues
in
plants
is
adequately
understood.
Acceptable
metabolism
studies
on
citrus
and
cotton
have
been
submitted
by
the
MAATF
and
reviewed
by
the
Agency.
The
citrus
and
cotton
studies
were
conducted
using
MSMA
labeled
with
14C
in
the
methyl
group
as
the
test
substance.
The
Agency
previously
specified
that
translation
of
MSMA
metabolism
studies
to
DSMA
(
and
CAMA)
is
acceptable,
according
to
a
Phase
4
response
(
Christina
Olinger,
March
26,
1991).
The
results
of
these
reviewed
studies
were
presented
on
December
19,
1994
to
the
HED
Metabolism
Committee
(
Christina
Swartz,
January
26,
1995).
Based
on
the
metabolism
studies
conducted
by
the
registrants
for
MSMA,
as
well
as
metabolism
data
for
MSMA
and
DSMA
from
published
sources,
the
Committee
concluded
that
the
residues
of
concern
(
i.
e.,
that
which
is
of
toxicological
concern
and
requires
regulation)
associated
with
the
use
of
MSMA,
DSMA,
and
CAMA
are
MMA
per
se
and
DMA
expressed
as
As2O3.
This
decision
was
predicated
on
the
low
rate
or
lack
of
demethylation,
and
the
inability
to
distinguish
between
background
arsenic
and
arsenic
resulting
from
pesticide
use.
Since
the
Agency
is
Page
30
of
125
required
to
consider
all
sources
of
arsenic
under
FQPA,
speciated
(
MMA,
DMA,
iAs)
monitoring
data
would
be
useful.

The
qualitative
nature
of
MMA
residues
in
animals
is
adequately
understood
based
on
acceptable
ruminant
and
poultry
metabolism
studies.
The
HED
Metabolism
Committee
(
Swartz
1995)
concluded
that
there
was
no
reasonable
expectation
of
finite
residues
of
concern
in
meat,
milk,
poultry,
and
eggs
as
a
result
of
registered
uses;
that
is,
residues
in
meat,
milk,
poultry,
and
eggs
could
be
classified
under
Category
3
of
CFR
§
180.6(
a).
Tolerances
and
feeding
studies
are
not
required
at
this
time.
However,
if
warranted,
this
will
be
revisited
in
the
future.

3.3
Environmental
Fate
Environmental
fate
laboratory
studies
show
that
organic
arsenicals
are
stable
under
all
tested
abiotic
conditions.
Registrant
submitted
studies
of
DMA
and
MMA
found
both
compounds
to
be
stable
to
hydrolysis
at
all
pHs
(
MRID#
s
42059201
and
42363001).
DMA
and
MMA
were
also
found
to
be
stable
to
photolysis
in
both
aquatic
and
soil
environments
(
DMA:
MRID#
s
41662601
&
41662602;
MMA:
MRID#
s
41903902
&
41903901).
These
conclusions
are
supported
by
multiple
open
literature
studies
of
organic
arsenical
soil
metabolism
in
which
no
degradation
occurred
in
sterile
control
soils
(
see
Moore
2006).

Organic
arsenicals
are
subject
to
microbial
metabolism
in
soil
under
aerobic
or
anaerobic
conditions.
The
occurrence,
rate,
and
products
of
this
metabolism
are
variable,
dependent
on
environmental
conditions.
The
observed
persistence
of
organic
arsenicals
in
aerobic
soil
has
ranged
from
weeks
to
years,
depending
on
soil
properties
and
ambient
conditions
such
as
soil
moisture,
temperature,
chemical
concentration,
and
amount
of
organic
matter
(
Moore
2006).
The
extreme
of
this
range
is
seen
in
several
registrant
submitted
studies
of
microbial
metabolism
which
observed
no
transformation
at
all
(
MRID#
s
42616001,
42572601,
43036101).
These
studies
demonstrate
that
there
are
conditions
in
which
metabolism
does
not
occur,
possibly
due
to
non­
viable
soils,
but
there
is
well
established
evidence
of
organic
arsenical
metabolism
in
many
environments.
Therefore,
this
assessment
is
based
on
the
understanding
that
transformation
of
organic
arsenicals
is
an
important,
although
variable,
process.

Adding
to
the
complexity
is
that
metabolism
rates
do
not
appear
to
depend
linearly
on
organic
arsenical
concentration;
in
some
studies,
degradation
decreased
with
increasing
concentration
while
in
others,
concentration
had
no
effect
on
degradation.
Hence,
the
kinetics
is
not
necessarily
first­
order,
and
"
half­
life"
is
therefore
not
necessarily
an
appropriate
constant
for
all
concentrations.
Keeping
this
uncertainty
in
mind,
EFED
calculated
first­
order
half­
lives
to
use
in
the
exposure
modeling
and
as
a
convenient
measure
to
compare
results
from
laboratory
studies.
Based
on
several
studies
showing
estimated
first­
order
"
half­
lives"
in
aerobic
and
anaerobic
soils
ranging
from
months
to
nearly
a
year,
a
calculated
aerobic
soil
half­
life
of
240
days
was
used
in
modeling
for
both
DMA
and
MMA
(
see
Moore
2006).

Some
of
the
variability
in
degradation
processes
is
associated
with
variability
in
sorption
processes.
Soil
microbial
degradation
of
organic
arsenicals
only
occurs
while
the
compounds
Page
31
of
125
remain
dissolved
in
pore
water.
As
the
arsenicals
sorb
to
soil,
they
become
less
accessible
to
microbes
and
therefore
less
likely
to
be
degraded.
Sorption
variability
is
largely
controlled
by
soil
properties
including
the
clay
content,
the
iron
and
aluminum
content,
and
the
soil
pH.
It
has
also
been
shown
that
microbial
activity
can
slow
sorption.
With
changing
environmental
conditions,
arsenicals
can
also
desorb
and
become
available
for
degradation,
although
it
has
been
shown
that
over
time,
sorbed
arsenic
species
become
more
tightly
bound
to
soil.

The
effects
of
other
environmental
factors
on
the
rate
of
organic
arsenical
degradation
are
complex
and
poorly
defined
with
different
studies
leading
to
conflicting
results.
An
increase
in
temperature
has
been
shown
to
lead
to
increased
degradation,
but
results
on
the
impact
of
soil
organic
matter
or
applied
organic
arsenical
concentrations
are
contradictory.
The
influence
of
aerobic
versus
anaerobic
conditions
on
degradation
rates
is
also
ambiguous.
What
is
consistent,
in
both
literature
and
submitted
fate
studies,
is
the
great
influence
of
soil
environmental
conditions
on
transformation
rates.

3.3.1
Degradation
(
Metabolites)

Potential
metabolites
of
applied
DMA
and
MMA
include
volatile
alkylarsines
and
inorganic
arsenic
(
as
arsenate
or
arsenite)
along
with
carbon
dioxide.
Cacodylic
acid
may
be
present
as
a
metabolite
of
MMA
as
well
as
an
applied
parent
compound.
The
major
metabolites
identified
in
published
sources
and
registrant
submissions
are
inconstant­­
sometimes
detected
and
sometimes
not.
They
also
occur
in
widely
variable
proportions.
Reasons
for
this
are
unclear,
but
are
most
likely
associated
with
the
exquisite
sensitivity
to
the
ambient
conditions
mentioned
above.
Regardless,
it
is
crucial
not
to
confuse
transformation
with
detoxification.
These
arsenicals
and
their
transformation
products,
in
combination
with
arsenic
from
the
natural
background
and
from
other
anthropogenic
sources,
maintain
the
total,
immutable
arsenic
environmental
load.
Arsenic
from
pesticides
is
not
lost
but
redistributed
and
transformed
throughout
the
environment
(
plants,
animals,
air,
soil,
sediment,
water)
into
other
arsenic
containing
substances.

The
only
metabolism
pathway
that
could
directly
reduce
soil
arsenic
loading
is
transformation
to
volatile
alkylarsines.
Microbial
species
capable
of
metabolizing
dissolved
organic
arsenical
compounds
to
gaseous
arsines
have
been
identified
and
dimethylarsine
and
trimethylarsine
are
the
most
likely
volatile
products
of
soil
metabolism.
Metabolism
to
volatile
alkylarsines
is
possible
under
certain
conditions
but,
is
generally
not
likely
to
be
a
major
route
of
dissipation.
The
possibility
of
volatilization
was
therefore
not
included
in
calculations
on
the
fate
of
applied
organic
arsenical
pesticides.

Other
routes
of
metabolism
include
methylation
and
demethylation.
DMA
has
two
methyl
groups
attached
to
a
central
arsenic,
MMA
has
one,
and
inorganic
arsenic
has
none.
Theoretically,
any
of
the
methyl
groups
on
DMA
or
MMA
are
subject
to
removal,
while
one
methyl
group
could
be
added
to
convert
inorganic
arsenic
to
MMA
which
could
be
further
methylated
to
DMA.
However,
not
all
of
these
transformations
are
likely
to
occur
(
see
Moore
2006).
Studies
show
that
to
a
varying
degree,
MMA
may
lead
to
both
DMA
and
inorganic
arsenic
as
end
products.
Although
fewer
speciated
studies
are
available
for
DMA,
it
appears
that
Page
32
of
125
it
can
degrade
to
inorganic
arsenic
but
no
transformation
to
MMA
is
expected.
There
is
some
uncertainty
associated
with
all
studies
relying
on
speciation
of
soil
arsenic
due
to
limitations
in
extraction
and
analytical
techniques.
Arsenical
species
may
be
transformed
to
some
extent
during
the
process
of
extraction
and
measurement.
This
is
not
an
issue
when
results
are
reported
as
total
arsenic,
as
done
in
many
studies,
but
those
results
are
less
useful
in
a
discussion
of
metabolites.

Inorganic
forms
of
arsenic
are
more
toxic
than
the
organic
forms,
so
it
is
very
important
to
assess
the
possibility
of
transformation/
mineralization
of
organic
arsenical
pesticides
to
arsenate
[
AsV]
and
arsenite
[
AsIII].
As
with
all
organic
arsenical
degradation
processes,
conversion
to
inorganic
arsenic
is
extremely
variable.
Results
of
multiple
studies
range
from
no
mineralization
to
approximately
80%
mineralization.
Monitoring
of
residual
arsenic
in
areas
where
organic
arsenical
pesticides
have
been
applied
support
the
conclusion
that
significant
conversion
to
inorganic
arsenic
can
occur.

3.3.2
Mobility
In
Air.
Based
on
physical
properties
tabulated
above
in
section
2.0,
volatilization
of
parent
materials
would
not
expected
to
be
a
significant
route
of
dispersal.
Consistent
with
this
expectation,
volatilization
of
parent
was
not
reported
in
any
lab
study.
However,
as
mentioned
above,
volatile
arsines
produced
by
metabolism
are
part
of
the
global
arsenic
transformation
and
transport
cycle.

In
Soil.
Sorption
to
numerous
diverse
soils
varies
tremendously
but
indicates
intermediate
to
low
mobility.
Sorption
appears
to
be
independent
of
organic
matter
content;
rather,
it
is
higher
in
soils
with
higher
percentages
of
clay
or
with
more
iron
or
aluminum
content.
pH
could
have
a
major
influence
on
sorption
because
of
the
anionic
nature
of
the
tested
chemicals.
However,
available
data
show
that
in
the
more
environmentally
relevant
range
of
pHs
from
5
to
8.5,
sorption
of
organic
arsenicals
should
not
decrease
(
increase
mobility)
dramatically
with
pH
when
compared
to
the
much
larger
variability
in
soil
sorption
found
with
different
types
of
soils.

3.3.3
Soil
Buildup/
Persistence
The
relative
immobility
of
arsenicals
along
with
arsenic's
elemental
nature
lends
to
buildup
in
soil
after
repeated
applications
an
important
consideration.
Arsenic
does
not
break
down;
it
can
only
be
redistributed
through
runoff,
leaching,
erosion,
volatilization,
or
plant
uptake.
Arsenic
sorbs
strongly
to
soil
so
significant
leaching
is
unlikely
in
most
conditions
and
the
potential
for
runoff
is
likely
to
decrease
over
time.
Volatilization
is
also
likely
only
in
specific
circumstances,
leaving
soil
erosion
and
plant
uptake
as
the
sole
routes
of
dissipation
of
organic
arsenicals
applied
to
soil.

Submitted
studies
(
reviewed
by
EFED)
show
that,
except
for
at
high
application
rates,
a
single
year
of
application
is
unlikely
to
lead
to
significant
buildup
of
soil
arsenic,
but
they
show
that
a
large
fraction
of
applied
arsenic
remains
in
the
top
layers
of
soil.
After
repeated
applications
for
Page
33
of
125
multiple
years,
then,
soil
arsenic
levels
could
be
expected
to
increase,
making
the
possibility
of
soil
buildup
a
long
term
concern.

Because
long
term
impacts
are
of
concern,
it
is
important
to
look
at
studies
conducted
over
a
longer
period
of
time.
A
review
of
the
open
literature
by
EFED
found
several
long
term
field
dissipation
studies
with
some
reporting
no
arsenic
buildup
despite
very
high
application
rates
and
others
finding
substantial
buildup
at
rates
similar
to
current
labels.
Additional
information
about
the
potential
for
arsenic
soil
buildup
comes
from
monitoring
studies
in
areas
where
organic
arsenicals
are
known
to
be
used.
Levels
of
soil
arsenic
were
found
to
be
higher
than
background
arsenic
levels
in
several
Florida
golf
courses
and
in
highway
rights
of
way
in
Louisiana.
These
results
are
inconclusive
as
to
the
source
of
the
arsenic
buildup,
but
they
add
to
the
weight
of
evidence
from
controlled
field
studies
and
modeling.

Soil
accumulation
values
are
generated
by
PRZM
as
part
of
the
process
of
modeling
runoff
concentrations.
PRZM
was
run
with
a
modified
version
of
the
pe4
v01
shell
program
to
estimate
soil
accumulation
(
see
Moore
2006).
With
some
exceptions,
the
modeling
inputs
were
the
same
as
those
described
for
surface
water
modeling
(
see
Moore
2006).
Maximum
application
rates
for
MMA
on
turf
and
cotton
and
for
DMA
on
turf
were
used
and
the
modeling
assumed
median
sorption.
Because
of
limitations
in
the
available
data
and
modeling
capabilities,
soil
concentrations
were
modeled
as
total
arsenic,
rather
than
speciated
forms.
Application
rates
were
therefore
calculated
to
represent
applied
arsenic
and
infinite
half­
lives
were
used
to
capture
all
forms
of
arsenic
that
may
be
present.
A
wide
range
of
sorption
is
possible;
lower
sorption,
used
to
provide
protective
estimates
for
surface
water
modeling,
would
lead
to
lower
soil
concentrations,
while
greater
sorption
leading
to
higher
concentrations
is
also
possible.
The
possibility
of
transformation
to
volatile
species
was
not
included
in
modeling,
and
modeling
does
not
account
for
plant
uptake.
The
results
presented
are
for
the
scenarios
that
led
to
the
highest
soil
concentrations
(
PA
turf
and
NC
cotton).

In
the
top
10
cm
of
soil,
modeling
predicts
that
arsenic
will
accumulate
with
very
little
dissipation
for
several
years
and
then
level
off.
Over
the
long
term,
the
buildup
of
total
arsenic
from
MMA
application
is
predicted
to
reach
chronic
concentrations
of
approximately
13
ppm
and
45
ppm
on
cotton
and
turf,
respectively.
For
DMA
on
turf,
the
highest
application
rate
leads
to
a
modeled
chronic
soil
concentration
of
approximately
77
ppm,
assuming
annual
application
at
that
rate.
The
application
rate
for
other
non­
crop
uses
is
significantly
higher
than
that
for
turf.
For
DMA
on
cotton,
the
chronic
soil
concentration
is
2
ppm.
"
Chronic"
concentrations
are
the
upper
90th
percentile
confidence
limit
on
the
annual
average,
or
the
1­
in­
10
year
peak
annual
concentration.
If
deeper
soils
are
included,
the
overall
concentrations
would
be
lower.
Most
studies
suggest
that
concentrations
are
highest
in
the
surface
layers
and
buildup
is
typically
limited
to
the
top
30
cm.

The
same
issue
of
arsenic
buildup,
supported
for
soil
by
field
studies,
monitoring,
and
modeling,
is
relevant
to
concentrations
of
arsenic
in
sediment.
Arsenic
that
reaches
surface
water
is
likely
to
end
up
in
sediments.
A
registrant
study
in
an
aerobic
aquatic/
sediment
system
found
that
after
30
days,
25%
of
applied
DMA
was
found
in
the
sediment
(
MRID#
43036101).
For
MMA,
39%
Page
34
of
125
of
the
applied
amount
ended
up
in
sediment
after
30
days,
with
most
of
it
out
of
the
water
within
the
first
week
(
MRID#
43314801).
In
an
anaerobic
system,
after
1
year
61
to
95%
of
applied
MMA
was
found
in
the
sediment
(
MRID#
44767602).
For
DMA,
approximately
95%
of
the
applied
amount
was
found
in
the
sediment
after
one
year,
with
most
of
it
reaching
there
within
the
first
month
(
MRID#
42572601).
A
literature
review
of
arsenic
fate
reported
that
in
Lake
Michigan,
arsenic
concentrations
in
water
were
generally
much
less
than
in
the
sediments,
and
referred
to
oceanic
sediments
as
"
the
ultimate
sink
for
arsenic"
(
Moore
2006).

4.0
Hazard
Characterization/
Assessment
4.1
Overview
and
Background
The
text
and
tables
below
were
summarized
or
extracted
from
various
sources
including
data
evaluation
records
developed
for
the
studies
noted
below
for
MMA
and
DMA,
EPA's
special
metabolism
and
mode
of
action
paper
on
DMA
(
USEPA
2006)
,
and
the
scientific
literature.
EPA's
special
metabolism
and
mode
of
action
paper
on
DMA
(
USEPA
2006)
provides
a
detailed
description
of
the
metabolic
profiles
of
MMA
and
DMA
in
most
mammals,
including
rodents
and
humans;
the
mode
of
action
for
the
development
of
rat
bladder
tumors;
the
human
relevance
of
the
animal
mode
of
action;
and
the
dose­
response
considerations
for
DMA's
mode
of
action.
The
current
document
provides
only
a
brief
summary
of
the
information
contained
in
the
special
issue
paper.
For
details
regarding
these
topics,
including
the
benchmark
dose
analysis
for
DMA,
the
reader
is
referred
to
 
USEPA
(
2006).
Revised
Science
Issue
Paper:
Mode
of
Carcinogenic
Action
for
Cacodylic
Acid
(
Dimethylarsinic
Acid,
DMAV)
and
Recommendations
for
Dose
Response
Extrapolation.
January
30,
2006.

Toxicokinetic
factors
(
i.
e.,
absorption,
distribution,
metabolism,
and
excretion)
play
critical
roles
in
the
evaluation
of
quantitative
dose­
response
relationships
since
these
factors
influence
the
amount
of
chemical
at
the
site
of
action,
along
with
the
time
course
for
exposure
at
that
site.
The
in
vivo
metabolism
of
inorganic
arsenic
and
its
methylated
forms
involves
alternating
steps
in
which
trivalent
arsenic
is
oxidatively
methylated
and
then
reduced
from
pentavalency
to
trivalency
(
Figure
3.1a).
This
process
occurs
inside
the
body
in
a
primarily
one­
way
direction
such
that
direct
exposure
to
MMA
or
DMA
is
not
expected
to
lead
to
internal
exposure
to
inorganic
arsenic.
Data
from
in
vivo
and
in
vitro
metabolism
and
pharmacokinetic
(
PK)
studies
with
various
species
indicate
that
the
cellular
uptake
and
efficiency
of
methylation
differs
by
the
administered
or
exogenous
arsenical
compound.
Because
of
the
predominately
one­
directional
nature
of
the
pathway
in
mammals,
following
direct
exposure
to
pentavalent
MMA
or
pentavalent
DMA
(
e.
g.,
MMAV
or
DMAV,
respectively)
the
number
of
biologically
active
metabolic
products
is
expected
to
be
smaller
compared
to
direct
ingestion
of
iAs
(
Figure
3.1a).
For
example,
environmental
exposure
to
pentavalent
iAs
(
e.
g.,
iAsV)
may
result
in
an
internal
mixture
of
multiple
biologically
active
metabolic
products
[
iAsV,
iAsIII,
MMAV,
MMAIII,
DMAV,
DMAIII,
and
TMAO)].
However,
following
ingestion
of
DMAV,
metabolism
to
DMAIII
Page
35
of
125
and
TMAO
can
occur
(
Figure
3.1a).
Thus,
the
toxicokinetics
and
toxicodynamics
for
MMAV
and
DMAV
are
simpler
compared
to
the
internal
mixture
following
exposure
to
iAs.

In
vivo
and
in
vitro
toxicity
studies
indicate
that
the
various
arsenical
compounds
have
distinct
toxicological
profiles.
For
example,
exposure
to
high
levels
of
inorganic
arsenic
in
drinking
water
results
in
a
variety
of
adverse
health
effects
including
diabetes
mellitus,
cardiovascular
disease,
renal
disease,
vascular
skin
lesions
and
cancer,
and
lung,
liver
and
bladder
cancer.
Long­
term
animal
studies
with
MMA
suggest
that
the
large
intestine
is
the
target
organ
with
no
neoplastic
lesions
observed
at
any
site.
DMA
causes
bladder
tumors
in
rats
after
feeding
or
drinking
water
exposures.
Many
of
the
toxicological
activities
of
the
pentavalent
and
trivalent
arsenical
compounds
are
shown
in
Figure
3.1a.
Because
of
the
distinct
PK
and
pharmacodynamic
(
PD)
differences
that
are
observed
following
direct
oral
exposure
to
MMA
and
DMA,
it
is
appropriate
to
use
chemical­
specific
data
for
extrapolating
risk
for
these
pesticides.

Under
the
FQPA,
only
those
chemicals
with
a
common
mechanism
of
toxicity
are
considered
in
cumulative
risk
assessment.
In
the
case
of
the
DMA,
the
mode
of
action
for
the
development
of
bladder
tumors
in
rats
has
been
elucidated.
Understanding
the
mode(
s)
of
action
for
inorganic
arsenic
is
complicated
by
the
mixture
of
toxic
metabolites
that
result
in
vivo.
The
mode
or
mechanism
of
action
for
cancer
and/
or
non­
cancer
effects
from
exposure
to
inorganic
arsenic
and
from
direct
exposure
to
MMA
have
not
yet
been
elucidated.
Some
have
hypothesized
that
multiple
modes
of
action
may
influence
the
toxicity
of
inorganic
arsenic.
Moreover,
because
of
the
PK
and
PD
differences
noted
above,
inorganic
arsenic,
MMA,
and
DMA
are
not
expected
to
exhibit
the
same
mode
or
mechanism
of
toxicity.
Thus,
the
risk
to
direct,
exogenous
exposure
to
MMA
and
DMA
should
not
be
summed
in
a
cumulative
risk
assessment.

4.2
MMA
4.2.1
Database
Summary
The
database
of
toxicology
studies
for
MMA
is
adequate
for
risk
assessment
purposes.
No
additional
studies
are
required
at
this
time.
As
MMA
is
an
in
vivo
metabolite
of
inorganic
arsenic,
there
is
extensive
data
evaluating
the
pharmacokinetics
and
metabolism
of
MMA
in
various
species
in
addition
to
extensive
in
vitro
metabolism
and
toxicity
studies.
Acceptable
animal
toxicity
studies
include:
subchronic
dermal
toxicity,
chronic
toxicity
following
oral
exposure
in
rodents
and
non­
rodents,
developmental
toxicity
in
rat
and
rabbit,
reproductive
toxicity,
and
genotoxicity/
mutagenicity.
There
are
no
acute
studies
in
animals
which
studied
sub­
lethal
doses.
However,
an
acute
study
is
not
required
at
this
time
since
clinical
signs
consistent
with
acute
toxicity
were
noted
within
2­
5
hours
of
each
days
dosing
in
the
first
week
of
the
dog
study.
A
subchronic
toxicity
study
via
the
inhalation
route
is
not
available
for
MMA
or
the
pesticidal
salts
(
i.
e.;
MSMA,
DSMA,
and
CAMA).
This
study
is
not
required
at
this
time.
It
is
preferred
to
use
route­
specific
and
chemical­
specific
studies
in
the
risk
assessments.
For
screening
purposes,
an
inhalation
study
with
DMA
where
port
of
entry
effects
of
the
nasal
turbinates
were
noted
is
being
using
as
surrogate
data
for
MMA.
There
are
no
studies
which
Page
36
of
125
observed
toxic
effects
of
MMA
in
humans
and
there
are
no
epidemiology
studies
with
MMA.
There
is
one
metabolism
study
where
human
subjects
ingested
MMA
and
urinary
metabolites
were
measured
(
Buchet
et
al,
1981).

4.2.2
Toxicological
Effects
The
target
organs
following
oral
exposure
of
MMA
are
believed
to
be
the
gastrointestinal
tract,
particularly
the
large
intestine.
Effects
such
as
histopathology
of
the
cecum,
rectum,
and/
or
colon
were
noted
as
the
most
sensitive
effects
in
chronic
exposure
to
rats.
Diarrhea
and
vomiting,
suggesting
irritation
of
the
gastrointestinal
tract
were
noted
in
the
chronic
dog
study
in
the
first
week
of
dosing
and
continued
throughout
the
study.
Histopathology
of
the
kidney
was
also
noted
in
the
dog
and
mouse
after
chronic
exposure.

Following
21
days
of
dermal
exposure
in
rabbit
to
MMA,
there
were
no
toxicologically
relevant
effects
noted
systemically
or
dermally
up
to
1000
mg/
kg/
day.

As
stated
above,
no
neurotoxicity
studies
are
available
for
MMA
at
this
time.
There
is
no
evidence
of
neurotoxicity
observed
in
rat,
rabbit,
or
dog.
In
the
104­
week
oncogenicity
study
in
mice,
at
high
doses
(
46
and
104
mg/
kg/
day),
female
mice
exhibited
increased
incidences
of
hypersensitivity
and
tonic
convulsions.
At
the
same
dose,
body
weight
gain,
increased
water
consumption,
and
histopathology
of
the
large
intestine
and
kidney
were
also
noted
in
mice,
suggesting
significant
toxicity
to
the
animals.
It
is
also
notable
that
the
hypersensitivity
and
tonic
convulsions
were
at
doses
approximately
20­
fold
higher
than
those
resulting
in
clinical
signs
and
kidney
histopathology
observed
in
the
dog.

There
is
no
quantitative
or
qualitative
evidence
of
increased
susceptibility
of
rats
or
rabbit
fetuses
to
in
utero
exposure
in
available
developmental
toxicities.
In
the
rabbit
developmental
toxicity
study,
developmental
variations
were
observed
at
doses
similar
to
those
resulting
in
maternal
toxicity.
These
developmental
effects
included
an
increased
incidence
of
skeletal
variations
in
the
numbers
of
13th
thoracic
vertebra
with
ribs
and
8th
lumbar
vertebra
at
12
mg/
kg/
day.
At
12
mg/
kg/
day,
abortions
in
two
rabbits
were
attributed
to
decreased
body
weight
gain
(
mean
­
75%
compared
to
control).
The
maternal
toxicity
LOAEL
is
12
mg/
kg/
day,
based
on
decreased
body
weight,
food
consumption
(
during
the
dosing
period),
and
abortions.
The
maternal
toxicity
NOAEL
is
7
mg/
kg/
day.
The
developmental
NOAEL
is
7
mg/
kg/
day.
In
the
rat
developmental
toxicity
study,
developmental
effects
were
observed
at
doses
greater
than
maternally
toxic
doses.
In
the
rat
developmental
toxicity
study,
the
developmental
NOAEL
of
100
mg/
kg/
day
is
based
on
decreased
fetal
body
weight
observed
at
500
mg/
kg/
day.
The
maternal
NOAEL
of
10
mg/
kg/
day
is
based
on
decreased
body
weight
gains
and
food
consumption
observed
at
100
and
500
mg/
kg/
day.

Results
of
reproductive
toxicity
studies
with
MMA
indicate
that
effects
on
reproductive
performance
occur
only
at
high
doses,
higher
than
those
resulting
in
gastrointestinal
and
kidney
effects.
In
the
reproductive
toxicity
study,
whole
litter
loss
was
noted
in
the
300
ppm
(
F2
generation
only)
and
1000
ppm
dose
groups
(
F1
and
F2;
approximately
21.2
mg/
kg/
day
and
Page
37
of
125
75.8/
88.6
mg/
kg/
day,
respectively).
At
doses
similar
to
those
used
in
the
reproductive
toxicity
study,
in
the
chronic
rat
toxicity
study,
beginning
at
week
4­
5,
diarrhea
was
observed
in
all
rats
at
1000
ppm
and
in
27/
60
males
and
45/
60
females
of
the
400
ppm
groups.
The
observations
in
the
chronic
rat
study
suggest
that
the
rats
in
the
reproductive
toxicity
study
may
have
experienced
significant
toxicity.
There
are
two
literature
studies
(
Lopez
and
Judd,
1979;
Prukop
and
Savage,
1986)
which
observed
reproductive
performance
in
mice.
These
studies
provide
information
regarding
overall
characterization,
but
are
not
useful
for
dose­
response
assessment
due
to
the
sparsity
of
information
provided
and
high
doses
used.
For
example,
Lopez
and
Judd
(
1979)
observed
smaller
nest
building
in
mice
exposed
to
477
ppm
of
MSMA
in
tap
water
for
14
days.
In
the
oncogenicity
study
with
mice,
histopathology
of
the
large
intestine
and
kidney
was
noted
at
a
dose
lower
(
200
ppm)
than
used
by
Lopez
and
Judd
(
1979).
In
a
different
study,
Prukop
and
Savage
(
1986)
performed
a
one­
generation
reproduction
study
in
mice
using
doses
that
are
approximately
5­
and
50­
fold
higher
than
the
point
of
departure
selected
by
EPA
for
use
in
risk
assessment
for
chronic
dietary
and
short/
intermediate­
term
incidental
oral
exposure.

MMA
is
classified
as
"
not
likely"
a
human
carcinogen.
Studies
in
rats
and
mice
did
not
show
an
increased
tumor
incidence
at
any
tissue
site
in
either
species.
The
results
of
these
studies
have
also
been
summarized
by
Arnold
et
al.,
(
2003).
In
a
recent
study,
Shen
et
al.,
(
2003)
exposed
male
rats
to
MMA
at
0,
50,
or
200
ppm
in
drinking
water
for
104
weeks.
Although
incidence
of
GST­
P
positive
foci
in
the
liver,
and
urinary
bladder
hyperplasia,
were
observed
in
MMA
treated
animals,
there
was
no
increase
incidence
in
tumors
at
any
tissue
site.
The
acceptable
genetic
toxicology
studies
indicate
that
MAA
is
not
mutagenic
in
bacteria
(
Salmonella
typhimurium
)
or
cultured
mammalian
cells
(
Chinese
hamster
ovary).
Similarly,
MMA
did
not
induce
unscheduled
DNA
synthesis
(
UDS)
in
primary
rat
hepatocytes.
TABLE
4.2.2a:
Profile
of
Subchronic,
Chronic,
and
Other
Toxicity
of
MMA
and
Cacodylic
Acid
MMA
Cacodylic
Acid
Guideline
#

/
Study
Type
MRID#
(
year)

/
Classification/
Doses
Results
MRID#
(
year)

/
Classification/
Doses
Results
870.3100
90­
Day
oral
toxicity
40632601
(
1985)

Unacceptable/
Nonguideline
0,
10,
100,
500,
and
1250
ppm
(
0,

2.1,
22.5,
110.6,
and
288.6
mg/
kg/
day
for
males
and
0,
2.8,

27.5,
137.4,
and
342.5
mg/
kg/
day
for
females)

MMA
In
mice
Based
on
the
data
presented
in
this
study,
a
LOAEL
and
NOAEL
can
not
be
established.
The
numerous
deficiencies
in
the
conduct
of
this
study
preclude
meaningful
evaluation
of
the
data.
42767701
(
1987)

Acceptable/
Guideline
males:
0,
0.4,
4.0,
43.2
mg/
kg/
day
females:
0,
0.4,
4.5,
45.7
mg/
kg/
day
In
rats
NOAEL
=
0.4
mg/
kg/
day
LOAEL
=
4
(
males)
and
4.5
(
females)

mg/
kg/
day
based
on
increased
incidence
of
cuboidal
to
columnar
epithelial
lining
thyroid
follicles
and
increased
water
consumption
and
urine
output
and
decreased
specific
gravity;
and
decreased
hematology
parameters
in
females.

870.3200
21/
28­
Day
dermal
toxicity
41872701
(
1991)

Acceptable/
Guideline
0,
100,
300,
or
1000
mg/
kg/
day
MMA
In
rabbits
Systemic
toxicity
NOAEL
=
1000
Systemic
toxicity
LOAEL
>
1000
Dermal
irritation
NOAEL
=
1000
Dermal
irritation
LOAEL
>
1000
41872801
(
1991)

Acceptable/
Guideline
0,
100,
300,
1000
mg/
kg/
day
In
rabbits
NOAEL
=
300
mg/
kg/
day
LOAEL
=
1000
mg/
kg/
day
based
on
decreased
body
weight
gains
in
females,
and
decreased
testicular
weights,
hypospermia
and
tubular
hypoplasia
in
males.

870.3465
90­
Day
inhalation
toxicity
Not
available
for
MMA
44700301
(
1994)

Acceptable/
Guideline
0,
10,
34,
100
mg/
m3
0.
0.01,
0.03,
0.10
mg/
L
In
rats
NOAEL
=
0.010
mg/
L/
day
LOAEL
=
0.034
mg/
L/
day
in
both
male
and
female
rats
based
on
the
presence
of
moderate
and
marked
intracytoplasmic
eosinophilic
granules
(
IEG)
in
the
cells
of
the
nasal
turbinates.

870.3700a
Prenatal
developmental
41926401
(
1990)

Acceptable/
Guideline
0,
10,
100,
or
500
mg/
kg/
day
MMA
In
rats
Maternal
toxicity
NOAEL
=
10
mg/
kg/
day.

Maternal
toxicity
LOAEL
=
100
mg/
kg/
day,

based
on
decreased
body
weight
gain
and
food
consumption.

Developmental
toxicity
NOAEL=
100
mg/
kg/
day.
Developmental
toxicity
LOAEL
=
500
mg/
kg/
day,
based
on
decreased
mean
fetal
body
weight.
4062701
(
1988)

Acceptable/
Guideline
0,
4,
12,
36
mg/
kg/
day
(
gavage)

In
rats
Maternal
NOAEL
=
12
mg/
kg/
day
LOAEL
=
36
mg/
kg,
based
on
decreased
body
weights,
body
weight
gains,
food
consumption
and
gravid
uterine
weight.

Developmental
NOAEL
=
12
mg/
kg/
day
LOAEL
=
36
mg/
kg,
decreased
fetal
weights,

shorter
crown­
rump
length,
the
suggestion
of
diaphragmatic
hernia
and
delayed/
lack
of
ossification
of
numerous
bones.
TABLE
4.2.2a:
Profile
of
Subchronic,
Chronic,
and
Other
Toxicity
of
MMA
and
Cacodylic
Acid
MMA
Cacodylic
Acid
Guideline
#

/
Study
Type
MRID#
(
year)

/
Classification/
Doses
Results
MRID#
(
year)

/
Classification/
Doses
Results
870.3700b
Prenatal
developmental
15939001
(
1986)

Acceptable/
Guideline
0,
1,
3,
7,
12
mg/
kg/
day
MMA
In
rabbits
Maternal
toxicity
NOAEL
=
7
mg/
kg/
day.

Maternal
toxicity
LOAEL
=
12
mg/
kg/
day,

based
on
decreased
body
weight,
food
consumption
(
during
the
dosing
period),

and
abortions.
Developmental
toxicity
NOAEL
=
7
mg/
kg/
day.
Developmental
toxicity
LOAEL
=
12
mg/
kg/
day,
based
abortions
and
on
an
increased
incidence
of
skeletal
variations
(
increased
numbers
of
13th
thoracic
vertebra
with
ribs
and
8th
lumbar
vertebra).
40663301
(
1988)

Acceptable/
Guideline
0,
3,
12,
48
mg/
kg/
day
(
gavage)

In
rabbits
Maternal
NOAEL
=
12
mg/
kg/
day
LOAEL
=
48
mg/
kg/
day,
based
on
mortality,

abortions,
body
weight
loss
and
reduced
food
consumption.
Developmental
NOAEL
=
12
mg/
kg/
day
LOAEL
was
not
established,
since
no
pregnant
rabbit
survived
to
the
gestation
day
29
scheduled
sacrifice.

870.3800
Reproduction
and
fertility
effects
43178301
(
1994)

Acceptable/
Guideline
0,
100,
300,
or
1000
ppm.

F0:
5.8,
17.8,
and
63.5
mg/
kg/
day,

respectively,
for
males
and
7.5,

22.5,
and
77.6
mg/
kg/
day
for
females.

F1:
6.5,
21.1,
and
75.8
mg/
kg/
day,

respectively,
for
males
and
7.9,

25.4,
and
88.6
mg/
kg/
day
for
females.

MMA
In
rats
Parental
NOAEL
=
100
ppm
for
males
and
300
ppm)
for
females.

Parental
LOAEL
=
300
ppm
for
male
rats
and
1000
ppm
for
female
rats
based
on
increased
food
consumption
with
decreased
body
weight
gain
along
with
whole
litter
loss.
Reproductive
NOAEL
=
300
ppm.

Reproductive
LOAEL
>
300
ppm.

Offspring
NOAEL
=
100
ppm.

Offspring
LOAEL
=
300
ppm
based
on
increased
pup
death
(
day
0­
21),
reduced
litter
survival
index,
and
decreased
lactation
index
related
to
whole
litter
loss.
41059501
(
1989)

Acceptable/
Guideline
Males:
0,
0.31,
2.16,
15.5
mg/
kg/
day
Females:
0,
0.38,
2.48,
17.86
mg/
kg/
day
In
rats
Parental/
Systemic
NOAEL
=
Females:
2.48
mg/
kg/
day
LOAEL
=
Females:
17.86
mg/
kg/
day,
based
on
decreased
absolute
and
relative
ovarian
weights
and
increased
incidence
of
thyroid
follicles
lined
with
cuboidal
to
columnar
epithelium
in
females
only.

Reproductive
NOAEL
=
Females:
17.86
mg/
kg/
day
LOAEL
was
not
established
Offspring
toxicity:
There
was
no
suggestive
evidence
of
offspring
toxicity
in
either
generation.
TABLE
4.2.2a:
Profile
of
Subchronic,
Chronic,
and
Other
Toxicity
of
MMA
and
Cacodylic
Acid
MMA
Cacodylic
Acid
Guideline
#

/
Study
Type
MRID#
(
year)

/
Classification/
Doses
Results
MRID#
(
year)

/
Classification/
Doses
Results
870.4200b
Chronic
toxicity
40546101
and
41266401
(
1988)

Acceptable/
Guideline
0,
2.5,
10,
40
mg/
kg/
day
(
week
1
only)

0,
2,
8,
and
35
mg/
kg/
day
(
week
2­

52)
MMA
In
dogs
NOAEL
=
2
mg/
kg/
day.

LOAEL
=
8
mg/
kg/
day
based
on
based
on
body
weight
gain
and
kidney
effects
(
organ
weight
and
histopathology)
in
females
in
both
sexes
41490901
(
1989)

Acceptable/
Guideline
0,
6.5,
16,
40
mg/
kg/
day
(
gavage)

In
dogs
NOAEL
=
16
mg/
kg/
day
LOAEL
=
40
mg/
kg/
day
based
on
salivation,

vomiting,
diarrhea,
and
decreased
body
weight
gains
in
males
and
females;
and
decreased
HCT%,
HgB,
RBC
counts,
total
protein
and
albumin
in
males.

Benchmark
Dose
Estimates
for
Bladder
Effects
(
as
described
in
DMA
MOA
Paper,

USEPA,
2005b)

Tumors
104
weeks
BMD10
=

7.74
mg/
kg/
day
BMDL10
=

5.96
mg/
kg/
day
870.4300
Combined
Chronic/

Carcinogenicity
41669001
(
1990)

Acceptable
0,
50,
400
and
800­
1300
ppm
(
0,

3.2,
27.2,
and
93.1
mg/
kg/
day
for
males
and
0,
3.8,
32.9,
and
101.4
mg/
kg/
day
for
females)
for
104
weeks.

MMA
In
rats
NOAEL
=
50
ppm
(
3.2
mg/
kg/
day
for
males
and
3.8
mg/
kg/
day
for
females)

LOAEL
=
400
ppm
(
27.2
mg/
kg/
day
for
males
and
32.9
mg/
kg/
day
for
females)

based
on
decreased
body
weights,
body
weight
gains,
food
consumption,

histopathology
of
gastrointestinal
tract
and
thyroid.

Dosing
was
considered
adequate.
41862101
(
1989)

Acceptable/
Guideline
Males:
0,
0.14,
0.73,
2.80,
7.30
mg/
kg/
day
Females:
0,
0.16,
0.79,
3.20,
8.0
mg/
kg/
day
In
rats
Hyperplasia
10
weeks
BMD10
=

2.00
mg/
kg/
day
BMDL10
=

1.54
mg/
kg/
day
870.4300
Carcinogenicity
42173201
(
1991)

Acceptable
0,
10,
50,
200,
and
400
ppm
(
0,

1.8,
9.3,
38,
and
83
mg/
kg/
day
for
males
and
0,
2.2,
12,
46,
and
104
mg/
kg/
day
for
females)

MMA
In
mice
NOAEL
=
50
ppm
(
9.3
and
12
mg/
kg/
day)

for
males
and
females.

LOAEL
=
200
ppm
(
38
and
46
mg/
kg/
day)

for
males
and
females
based
on
decrease
in
body
weight
gain,
increased
water
consumption,
and
histopathology
of
the
kidney.

Dosing
was
considered
adequate.
41914601
(
1990)

Unacceptable
Males:
0,
1.47,
7.0,
35.25,
91.95
mg/
kg/
day
Females:
0,
1.7,
8.65,
43.15,
97.0
mg/
kg/
day
In
mice
NOAEL
=
1.7
(
Females)
and
7
(
Males)

mg/
kg/
day
LOAEL
=
8.65
(
Females)
and
35.25
(
Males)

mg/
kg/
day
based
on
vacuolar
degeneration
of
bladder
epithelium.
TABLE
4.2.2a:
Profile
of
Subchronic,
Chronic,
and
Other
Toxicity
of
MMA
and
Cacodylic
Acid
MMA
Cacodylic
Acid
Guideline
#

/
Study
Type
MRID#
(
year)

/
Classification/
Doses
Results
MRID#
(
year)

/
Classification/
Doses
Results
870.5100
Gene
mutation
Salmonella
typhimurium
reverse
gene
mutation
41651902
(
1989)

Acceptable/
Guideline
In
deionized
distilled
water
at
concentrations
of
667,
1000,
3333,

6667
and
10,000
µ
g/
plate
in
the
presence
and
absence
of
mammalian
metabolic
activation
(
S9­
mix).
MMA
There
was
no
evidence
of
induced
mutant
colonies
over
background.

870.5300
Gene
mutation
Mouse
lymphoma
assay
41651904
(
1989)

Acceptable/
Guideline
In
deionized
water
at
concentrations
of
300,
400,
534,

712,
949,
1266,
1688,
2250,
3000
and
4000
µ
g/
mL
in
the
absence
of
mammalian
metabolic
activation
(
S9­
mix)
and
at
concentrations
of
71,
95,
127,
169,
225,
300,
400,

534,
712,
949,
1266
and
1688
µ
g/
mL
in
the
presence
of
S9­
mix.

MMA
MMA
was
tested
up
to
cytotoxic
concentrations.
There
was
no
evidence
of
induced
mutant
colonies
over
background.

870.5375
Chromosomal
aberration
Mouse
micronucleus
assay
41651903
(
1989)

Acceptable/
Guideline
In
distilled
water
in
two
independent
assays.

Concentrations
tested
in
the
initial
assay
were
625,
1250,
2500,
5000
µ
g/
mL,

with
and
without
metabolic
activation
(
S9­
mix).
MMA
MMA
was
tested
up
to
a
slightly
cytotoxic
concentration,
limited
by
solubility
in
the
solvent,
distilled
water.
There
was
no
evidence
of
chromosomal
aberrations
induced
over
background.
Numerous
mutageniticy
and
genotoxicity
studies
with
DMA
and
DMAIII.
These
are
described
in
detail
in
USEPA,
2005b
(
See
Table
B4
in
the
DMA
MOA
paper).

Overall,
DMA
(
cacodylic
acid)
is
not
a
direct
acting
mutagen.
TABLE
4.2.2a:
Profile
of
Subchronic,
Chronic,
and
Other
Toxicity
of
MMA
and
Cacodylic
Acid
MMA
Cacodylic
Acid
Guideline
#

/
Study
Type
MRID#
(
year)

/
Classification/
Doses
Results
MRID#
(
year)

/
Classification/
Doses
Results
870.5550
Unscheduled
DNA
Synthesis
41651905
(
1989)

Acceptable/
Guideline
In
deionized
distilled
water
at
concentrations
of
10,
50,
100,
500,

750
and
1000
µ
g/
mL
for
18
to
20
hours
in
an
initial
and
a
confirmatory
assay.
MMA
There
was
no
evidence
that
unscheduled
DNA
synthesis,
as
determined
by
radioactive
tracer
procedures
[
nuclear
silver
grain
counts]
was
induced.

870.7485
Metabolism
and
pharmacokinetics
42010501
(
1991)

Acceptable/
Guideline
In
water
at
concentrations
of
0,
5.0,

or
200.0
mg/
kg
according
to
the
following
five
different
dose
groups:
1)
In
the
vehicle
control
group,
dosed
with
water
by
gavage;
2)
a
single
radiolabeled
gavage
dose
of
5.0
mg/
kg;
3)
a
single
radiolabeled
gavage
dose
of
200
mg/
kg;
4)
dosed
by
gavage
for
14
consecutive
days
with
unlabelled
MSMA
at
5.0
mg/
kg/
day
followed
by
a
single
radiolabeled
dose
of
MSMA
at
MSMA;
5)
a
single
radiolabeled
i.
v.
dose
of
5.0
mg/
kg.

MSMA
in
rats
Analysis
of
fecal
and
urinary
samples
by
HPLC
and
TLC
revealed
that
the
radioactivity
of
all
preparative
fractions
was
associated
with
parent
compound
and
two
unknown
metabolites.
The
major
product
excreted
in
both
urine
and
feces
was
unchanged
parent,
accounting
for
80­
97%

of
the
administered
dose.
42341301
&
43005801
(
1992)

Acceptable/
Guideline
Doses:
0,
5.0
and
50.0
mg/
kg
In
rats
Over
a
7­
day
period
90
­
98%
of
total
dose
was
excreted.
Total
radioactivity
recovered
in
the
urine,
feces
and
exhaled
air
was
28
­

82,
4
­
33,
and
0
­
0.1%,
respectively.

870.7600
Dermal
penetration
Not
available
for
MMA
43497401
(
1994)

Acceptable/
Guideline
Dose:
0,
0.90,
9.30,
or
91.3
µ
g/
cm2
In
rats
10
hour
dermal
absorption
is
3.5%
Page
43
of
125
TABLE
4.2.2b:
Acute
Toxicity
of
MSMA
Guideline
No.
Study
Type
MRID#
s
Results
Toxicity
Category
81­
1
Acute
Oral,
rat
45405601*
LD50
=
2449
mg/
kg
(
F)
3184
mg/
kg
(
M)
2833
mg/
kg
(
Combined)
III
81­
2
Acute
Dermal,
rabbit
41890001*
LD50
>
2000
mg/
kg
III
81­
3
Acute
Inhalation,
rat
42604601*
LC50
=
2.20
mg/
L
III
81­
4
Primary
Eye
Irritation,
rabbit
43840901*
Reversible
conjunctival
irritation
III
81­
5
Primary
Skin
Irritation,
rabbit
41892008a
Slight
irritant
IV
81­
6
Dermal
Sensitization,
guinea
pig
41890002*
Not
a
sensitizer
81­
8
Acute
Neurotoxicity
N/
A
*
Data
presented
in
table
are
for
formulations
containing
technical
MSMA.
a
DSMA
study
used
as
a
surrogate
TABLE
4.2.2c:
Acute
Toxicity
of
DSMA*

Guideline
No.
Study
Type
MRID#
s
Results
Toxicity
Category
81­
1
Acute
Oral,
rat
41892004
LD50
=
1935
(
1631­
2295)
mg/
kg
(
M&
F)
III
81­
2
Acute
Dermal,
rabbit
41892005
LD50
>
2000
mg/
kg
III
81­
3
Acute
Inhalation,
rat
41892006
LC50
>
6
mg/
L
IV
81­
4
Primary
Eye
Irritation,
rabbit
41892007
Redness
and
chemosis
of
the
conjunctivae
III
81­
5
Primary
Skin
Irritation,
rabbit
41892008
No
erythema
or
edema
IV
81­
6
Dermal
Sensitization,
guinea
pig
41890009
Not
a
sensitizer
81­
8
Acute
Neurotoxicity
N/
A
*
Data
presented
is
for
technical
DSMA.
Page
44
of
125
TABLE
4.2.2d:
Acute
Toxicity
of
CAMA*

Guideline
No.
Study
Type
MRID#
s
Results
Toxicity
Category
81­
1
Acute
Oral,
rat
42880201
LD50
>
5000
mg/
kg
(
M&
F)
IV
81­
2
Acute
Dermal,
rat
42900101
LD50
>
5000
mg/
kg
IV
81­
3
Acute
Inhalation,
rat
42900102
LC50
>
5
mg/
L
IV
81­
4
Primary
Eye
Irritation,
rabbit
42900202
Mild
eye
irritant
III
81­
5
Primary
Skin
Irritation,
rabbit
42900203
Slight
skin
irritant
IV
81­
6
Dermal
Sensitization,
rabbit
42900103
None
81­
8
Acute
Neurotoxicity
N/
A
*
Acute
oral
studies
listed
in
table
represent
a
formulation
with
10.3%
a.
i.

4.2.3
FQPA
Hazard
Considerations
Acceptable
developmental
studies
in
rats
and
rabbits
along
with
a
two­
generation
reproductive
toxicity
study
are
available
for
MMA.
Results
of
developmental
and
reproductive
toxicities
studies
provided
no
indication
of
increased
susceptibility
of
rat
or
rabbit.
The
toxicology
database
is
considered
complete
for
the
evaluation
of
sensitivity
of
the
developing
young.
A
developmental
neurotoxicity
study
is
not
required.
As
described
below,
toxicity
to
gastrointestinal
tract
and
kidney
provide
the
critical
effects
for
MMA
following
oral
exposures.
These
effects
are
more
sensitive
than
toxicities
noted
in
other
studies,
including
developmental
and
reproductive
toxicity
and
neurotoxicity.
Therefore,
the
FQPA
safety
factor
is
not
needed.

4.2.4
Dose­
Response,
Hazard
Identification
and
Toxicity
Endpoint
Selection
Toxicological
endpoints
are
needed
to
assess
potential
risk
to
MMA
from
the
following
durations
and
routes
of
exposure:

 
Acute
and
chronic
dietary
exposure,
 
Short­
and
intermediate­
term
incidental
oral
exposure,
 
Short­
and
intermediate­
term
dermal
exposure,
and
 
Short­
and
intermediate­
term
inhalation
exposure.

Although
the
mode
of
action
for
MMA
is
not
known,
toxicity
endpoints
relevant
to
the
target
tissues
provide
the
critical
endpoints
for
each
exposure
scenario.
Following
oral
exposures,
toxicity
to
the
gastrointestinal
tract
provide
the
critical
effects
for
MMA.
Diarrhea
and
vomiting,
suggesting
irritation
of
the
gastrointestinal
tract,
were
noted
in
the
chronic
dog
study
in
the
first
week
of
dosing
within
2­
5
hours
of
each
days
dosing
at
the
highest
dose
(
week
1
LOAEL
of
40
mg/
kg/
day).
In
the
absence
of
an
acute
toxicity
study
with
sub­
lethal
observations,
the
week
1
Page
45
of
125
NOAEL
of
10
mg/
kg
for
the
effects
noted
in
the
first
week
of
dosing
provide
the
most
appropriate
effects
for
acute
dietary
risk
assessment.

For
short­
term
incidental
oral
exposure,
toxicity
observed
in
the
does
from
the
rabbit
development
toxicity
study
provides
an
appropriate
endpoint.
Animals
in
the
rabbit
study
were
dosed
on
13
consecutive
days,
consistent
with
the
duration
of
interest
for
short­
term
incidental
oral
exposure
(
i.
e.
1­
30
days).
The
maternal
toxicity
LOAEL
is
12
mg/
kg/
day,
based
on
decreased
body
weight,
food
consumption
(
during
the
dosing
period),
and
abortions.
The
maternal
toxicity
NOAEL
is
7
mg/
kg/
day.

In
the
two­
year,
chronic
toxicity
study
in
rat,
the
LOAEL
of
27.2
mg/
kg/
day
is
based
on
decreased
body
weights,
diarrhea,
body
weight
gains,
food
consumption,
and
histopathology
of
gastrointestinal
tract
and
thyroid.
Diarrhea
and
body
weight
changes
were
noted
at
the
27.2
mg/
kg/
day
dose
level
following
approximately
4
to
7
weeks
of
exposure
and
are
therefore
reasonable
for
use
in
intermediate­
term
incidental
oral
risk
assessment.
Histopathology
was
observed
only
at
termination.
Thus,
the
NOAEL
of
3.2
mg/
kg/
day
is
appropriate
for
extrapolating
chronic
dietary
risk
assessment
and
intermediate­
term
incidental
oral
exposure.
It
is
notable
that
the
rat
NOAEL
for
chronic
toxicity
is
further
supported
by
the
NOAEL
observed
in
the
chronic
dog
study
(
2
mg/
kg/
day,
respectively).
The
effects
noted
in
the
chronic
study
in
the
rat
and
dog
chronic
studies
are
more
sensitive
than
those
noted
in
the
104­
week
study
with
mice
(
NOAEL
of
9.3
mg/
kg/
day).

Pharmacokinetics
of
absorption
and
metabolism
can
differ
among
oral,
dermal,
and
inhalation
exposures.
Because
of
this,
it
is
preferred
to
use
route­
specific
studies
when
extrapolating
risk.
Regarding
dermal
exposure,
the
MMA
dermal
toxicity
study
in
rat
indicates
no
toxicologically
relevant
effects
up
to
1000
mg/
kg/
day.
Regarding
inhalation
exposures,
the
rat
inhalation
study
with
DMA
has
been
selected
as
a
surrogate
for
MMA
in
the
absence
of
an
MMA
inhalation
toxicity
study.
This
provides
some
uncertainty
in
the
inhalation
risk
assessments
for
MMA.
As
described
in
the
EPA's
issue
paper
regarding
metabolism
and
mode
of
action
for
DMA,
the
pharmacokinetics
of
oral
exposure
to
DMA
and
MMA
differ
and
that
chemical
specific
data
are
preferred.
In
the
case
of
oral
exposure,
the
target
tissues
for
DMA
and
MMA
are
believed
to
be
different
(
bladder
vs.
gastrointestinal
tract).
In
the
90­
day
inhalation
toxicity
study
with
DMA,
port­
of­
entry
effects,
not
systemic
ones,
are
the
most
sensitive.
Both
DMA
and
MMA
cause
in
vitro
cytotoxicity
in
various
cell
lines
and
tissues.
The
cytotoxic
concentrations
are
within
the
same
ranges
for
the
pentavalent
DMA
and
MMA
(
USEPA
2006).
Although
the
relationship
between
cytotoxicity
and
nasal/
respiratory
irritation
is
not
known,
it's
a
reasonable
assumption
that
chemicals
which
cause
cytotoxicity
to
tissue
surfaces
may
also
be
irritating
to
the
respiratory
tract.
Moreover,
both
MMA
and
DMA
are
mildly
irritating
to
eyes.
For
some
pesticide
chemicals
where
no
inhalation
studies
are
available,
OPP
often
extrapolates
risk
using
oral
studies
with
the
assumption
of
100%
absorption.
This
approach
is
reasonable
for
chemicals
whose
toxicity
is
primarily
related
to
systemic
effects.
However,
for
MMA,
it
is
a
reasonable
assumption
that
MMA
may
cause
port
of
entry
effects
via
the
inhalation
route,
similar
to
DMA.
As
such,
use
of
an
oral
study
may
not
be
appropriate
in
this
case.
As
a
screening
approach,
the
DMA
inhalation
study
is
currently
being
used
as
a
surrogate
for
MMA
inhalation
toxicity.
In
the
event
that
the
use
pattern
or
exposure
profile
for
MMA
changes,
the
Agency
may
require
an
inhalation
toxicity
study
with
MMA
or
its
salts
in
the
future.
Page
46
of
125
Historically,
EPA
has
utilized
10X
factors
to
account
for
inter­
species
and
intra­
species
extrapolation/
uncertainty.
In
the
case
of
MMA,
there
are
not
sufficient
data
to
support
reduction
of
the
default
factors.
Therefore,
a
total
of
100X
will
be
applied
to
each
route
and
duration
of
MMA
exposure
to
account
for
inter­
species
and
intra­
species
extrapolation/
uncertainty.

4.2.4.1
Acute
Reference
Dose
(
aRfD)
­
General
Population
There
are
no
acute
oral
studies
which
considered
non­
lethal
doses
of
MMA
which
could
provide
endpoints
of
the
appropriate
duration
of
exposure
(
i.
e.
single
dose).
However,
in
the
chronic
oral
toxicity
study
in
dog
(
MRID#
s
40546101
and
41266401),
vomiting
and
diarrhea
were
observed
in
the
first
of
dosing
primarily
after
2­
5
hours
after
each
days
dosing.
The
timing
of
these
events
suggest
an
acute
effect
on
the
gastrointestinal
tract
following
gavage
administration
of
MMA.

In
the
chronic
oral
toxicity
study
in
dog,
MMA
was
administered
to
5
purebred
beagle
dogs/
sex/
group
by
capsule
at
dose
levels
of
0,
2.5,
10,
or
40
mg/
kg/
day
for
the
first
week
and
at
dose
levels
of
0,
2,
8,
and
35
mg/
kg/
day
for
the
remaining
51
weeks.
The
LOAEL
for
the
first
week
of
dosing
was
40
mg/
kg/
day
based
on
diarrhea
and
vomiting.
The
NOAEL
for
the
first
week
of
dosing
was
10
mg/
kg/
day.

4.2.4.2
Chronic
Reference
Dose
(
cRfD)

In
a
combined
chronic
toxicity/
carcinogenicity
feeding
study
(
MRID#
41669001),
MMA
was
administered
in
the
diet
to
60
Fischer
F344
rats/
sex/
dose
at
dose
levels
of
0,
50,
400
and
800­
1300
ppm
(
0,
3.2,
27.2,
and
93.1
mg/
kg/
day
for
males
and
0,
3.8,
32.9,
and
101.4
mg/
kg/
day
for
females)
for
104
weeks.
The
high­
dose
group
of
60
animals/
sex
received
1300
ppm
until
week
53.
Because
of
excessive
mortality
(
32%
of
males),
the
highest
dose
was
reduced
to
1000
ppm
until
week
60
and
to
800
ppm
for
the
remainder
of
the
study.
Beginning
at
week
4­
5,
diarrhea
was
observed
in
all
rats
at
the
highest
dose
level,
and
in
27/
60
males
and
45/
60
females
of
the
400
ppm
group.
Body
weights
were
statistically
decreased
from
week
7
through
termination
for
males
of
the
400
ppm
groups
and
from
week
4
through
termination
for
high­
dose
males.

The
chronic
LOAEL
was
400
ppm
(
27.2
mg/
kg/
day
for
males
and
32.9
mg/
kg/
day
for
females)
based
on
decreased
body
weights,
body
weight
gains
and,
food
consumption,
diarrhea
and,
histopathology
of
the
gastrointestinal
tract
and
thyroid.

4.2.4.3
Incidental
Oral
Exposure
(
Short
Term)

In
a
developmental
toxicity
study
(
MRID#
15939001),
MMA
was
administered
in
distilled
water
by
gavage
to
14
mated
New
Zealand
white
rabbits
per
group
at
doses
of
0,
1,
3,
or
7
mg/
kg/
day
on
gestation
days
(
GD)
7­
19,
inclusive.
Subsequent
groups
of
13­
14
mated
New
Zealand
white
rabbits
were
dosed
with
0
and
12
mg/
kg/
day
test
material.
The
maternal
toxicity
LOAEL
was
12
mg/
kg/
day,
based
on
decreased
body
weight,
food
consumption
(
during
the
dosing
period),
and
abortions.
The
maternal
toxicity
NOAEL
was
7
mg/
kg/
day.
Page
47
of
125
4.2.4.4
Incidental
Oral
Exposure
(
Intermediate
Term)

In
a
combined
chronic
toxicity/
carcinogenicity
feeding
study
(
MRID#
41669001),
MMA
was
administered
in
the
diet
to
60
Fischer
F344
rats/
sex/
dose
at
dose
levels
of
0,
50,
400
and
800­
1300
ppm
(
0,
3.2,
27.2,
and
93.1
mg/
kg/
day
for
males
and
0,
3.8,
32.9,
and
101.4
mg/
kg/
day
for
females)
for
104
weeks.
The
chronic
LOAEL
was
400
ppm
(
27.2
mg/
kg/
day
for
males
and
32.9
mg/
kg/
day
for
females)
based
on
decreased
body
weights,
and
diarrhea.
The
chronic
NOAEL
was
50
ppm
(
3.2
mg/
kg/
day
for
males
and
3.8
mg/
kg/
day
for
females).

4.2.4.5
Dermal
Exposure
(
Short
and
Intermediate
Term)

In
a
21­
day
dermal
toxicity
study
(
MRID#
41872701/
42659701),
MMA
(
99.4%
a.
i.,
Batch#
0030401)
was
administered
dermally
to
5
New
Zealand
white
rabbits/
sex/
group
at
doses
of
0,
100,
300,
or
1000
mg/
kg/
day
for
6
hours/
day,
5
days/
week
for
21
days.
The
systemic
toxicity
LOAEL
was
>
1000
mg/
kg/
day.
The
systemic
toxicity
NOAEL
=
1000
mg/
kg/
day.

There
was
no
edema
or
erythema
noted
at
the
exposure
sites
of
any
dose
group.
There
were
no
histological
dermatopathology
findings
at
the
1000
mg/
kg/
day
dose
level
as
compared
to
the
control
group.
The
dermal
irritation
LOAEL
was
>
1000
mg/
kg/
day.
The
dermal
irritation
NOAEL
=
1000
mg/
kg/
day.

4.2.4.6
Inhalation
Exposure
(
Short
and
Intermediate
Term)

In
a
90­
day
toxicity
study
(
MRID#
44700301),
DMA
[(
Cacodylate
3.25)
(
active
ingredients:
cacodylic
acid
(
4.9%)
and
sodium
cacodylate
(
28.4%);
batch
095/
93)]
was
administered
by
inhalation
to
10
rats/
sex/
dose
at
aerosol
concentrations
of
10,
34
and
100
mg/
m3
(
analytical
concentrations
0.01,
0.034,
or
0.1
mg/
L).
The
NOAEL
is
0.010
mg/
L/
day.
The
LOAEL
is
0.034
mg/
L/
day
in
both
male
and
female
rats
based
on
the
presence
of
moderate
and
marked
intracytoplasmic
eosinophilic
granules
(
IEG)
in
the
cells
of
the
nasal
turbinates.

4.2.5
Recommendation
for
Aggregate
Exposure
Risk
Assessments
The
FQPA
(
1996)
requires
that
EPA
aggregate
risks
from
multiple
pathways
as
part
of
tolerance
reassessment.
OPP
aggregates
risk
from
multiple
pathways
and
routes
in
cases
where
the
toxic
effect
of
interest
is
common
among
or
between
the
routes
of
interest.
In
the
case
of
MMA,
exposures
from
the
oral
route
(
food,
water,
incidental
oral)
may
be
aggregated.
As
no
effects
were
noted
in
the
MMA
dermal
toxicity
study
and
the
DMA
inhalation
toxicity
study
is
being
used
a
surrogate,
it
is
inappropriate
to
aggregate
risks
from
dermal
and
inhalation
exposures.

4.2.6
Classification
of
Carcinogenic
Potential
MMA,
or
its
sodium
or
calcium
salts,
have
been
classified
as
"
not
likely"
human
carcinogens.
Parathyroid
adenomas
were
noted
in
the
combined
chronic/
carcinogenicity
study
in
rats
for
Page
48
of
125
MMA.
These
tumors
were
outside
of
the
historical
controls.
However,
the
tumors
are
not
a
concern
because
1)
only
the
benign
tumors
were
increased
in
incidence;
2)
pair
wise
significance
was
not
attained
for
either
sex;
3)
an
increase
in
tumor
incidence
was
not
observed
in
mice;
and
4)
the
acceptable
genetic
toxicology
studies
indicate
that
MMA
is
not
mutagenic
in
bacteria
(
Salmonella
typhimurium)
or
cultured
mammalian
cells
(
Chinese
hamster
ovary).
Similarly,
MMA
did
not
induce
unscheduled
DNA
synthesis
(
UDS)
in
primary
rat
hepatocytes.

Table
4.2.4:
Summary
of
Toxicological
Doses
and
Endpoints
for
Chemical
for
Use
in
Human
Risk
Assessments
of
MMA
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
Acute
Dietary
(
general
population)
NOAEL
=
10
mg/
kg
UF
=
100
Acute
RfD
&
PAD
=
0.1
mg/
kg
Chronic
Toxicity
in
Dog,
MMA
study
(
MRID#
40546101)
LOAEL
=
40
mg/
kg/
day
based
on
clinical
signs
of
diarrhea
and
vomiting
observed
in
the
first
of
week
of
dosing
with
2­
5
hours
of
each
days
dosing.

Chronic
Dietary
(
all
populations)
NOAEL=
3.2
mg/
kg/
day
UF
=
100
Chronic
RfD
&
PAD
=

0.03
mg/
kg/
day
Chronic
Toxicity
Rat,
MMA
study
(
MRID#
41669001)
Rat
LOAEL
=
27.2
mg/
kg/
day
for
males
and
32.9
mg/
kg/
day
for
females
based
on
decreased
body
weights,
diarrhea,
body
weight
gains,
food
consumption,
histopathology
of
gastrointestinal
tract
and
thyroid.

Incidental
Oral
Short­
Term
(
1
­
30
days)
NOAEL=
7
mg/
kg/
day
LOC
=
100
Rabbit
developmental
toxicity
study
(
MRID#
15939001)
LOAEL
=
12
mg/
kg/
day,
based
on
decreased
body
weight,
food
consumption
(
during
the
dosing
period),
and
abortions.

Incidental
Oral
Intermediate­
Term
(
1
­
6
months)
NOAEL=
3.2
mg/
kg/
day
LOC
=
100
Chronic
Rat
study
(
MRID#
41669001)

LOAEL
=
27.2
mg/
kg/
day
for
males
and
32.9
mg/
kg/
day
for
females
based
on
decreased
body
weights,
diarrhea.

Dermal
Short­
Term
(
1
­
30
days)
Intermediate­
Term
(
1
­
6
months)
Dermal
NOAEL=
1000
mg/
kg/
day
LOC
=
100
21­
Day
Dermal
Toxicity
in
Rabbit,
MMA
study
(
MRID#
41872701)
LOAEL
>
1000
mg/
kg/
day.

Dermal
Long­
Term
(>
6
months)
Not
applicable
Inhalation
Short­
Term
(
1
­
30
days)
Intermediate­
Term
(
1
­
6
months)
Inhalation
NOAEL=
0.01
mg/
L
(
4.38
mg/
kg/
day,
adjusted)
LOC
=
100
90­
Day
Inhalation
with
DMA
­
Rat
(
MRID#
44700301)
LOAEL
=
0.034
mg/
kg/
L
(
14.95
mg/
kg/
day)
based
on
presence
of
moderate
and
marked
intracytoplasmic
eosinophilic
granules
(
IEG)
in
the
nasal
turbinate
cells
of
male
and
female
rats.

Cancer
Classification:
"
not
likely
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
Page
49
of
125
4.2.7
Endocrine
Disruption
EPA
is
required
under
the
FFDCA,
as
amended
by
FQPA,
to
develop
a
screening
program
to
determine
whether
certain
substances
(
including
all
pesticide
active
and
other
ingredients)
"
may
have
an
effect
in
humans
that
is
similar
to
an
effect
produced
by
a
naturally
occurring
estrogen,
or
other
such
endocrine
effects
as
the
Administrator
may
designate."
Following
recommendations
of
its
Endocrine
Disruptor
and
Testing
Advisory
Committee
(
EDSTAC),
EPA
determined
that
there
was
a
scientific
basis
for
including,
as
part
of
the
program,
the
androgen
and
thyroid
hormone
systems,
in
addition
to
the
estrogen
hormone
system.
EPA
also
adopted
EDSTAC's
recommendation
that
the
Program
include
evaluations
of
potential
effects
in
wildlife.
For
pesticide
chemicals,
EPA
will
use
FIFRA
and,
to
the
extent
that
effects
in
wildlife
may
help
determine
whether
a
substance
may
have
an
effect
in
humans,
FFDCA
authority
to
require
the
wildlife
evaluations.
As
the
science
develops
and
resources
allow,
screening
of
additional
hormone
systems
may
be
added
to
the
Endocrine
Disruptor
Screening
Program
(
EDSP).
In
the
available
toxicity
studies
on
MMA,
there
was
no
estrogen,
androgen,
and/
or
thyroid
mediated
toxicity.

4.3
DMA
4.3.1
Database
Summary
The
database
of
toxicology
studies
for
DMA
is
adequate
for
risk
assessment
purposes.
No
additional
studies
are
required
at
this
time.
Acceptable
animal
toxicity
studies
include:
subchronic
oral,
dermal,
and
inhalation
toxicity;
chronic
toxicity
following
oral
exposure
in
rodents
and
non­
rodents;
developmental
toxicity
in
rat
and
rabbit;
reproductive
toxicity;
and
genotoxicity/
mutagenicity.
Similar
to
MMA,
there
is
extensive
data
evaluating
the
pharmacokinetics
and
metabolism
of
DMA
in
various
species
in
addition
to
extensive
in
vitro
metabolism
and
toxicity
studies.
Moreover,
there
is
a
robust
database
of
studies
evaluating
the
mode
of
action
for
the
development
of
bladder
tumors
in
rats
(
See
USEPA
2006).
There
are
no
studies
which
observe
toxic
effects
of
DMA
in
humans
and
there
are
no
epidemiology
studies
with
DMA.
There
are
two
metabolism
studies
where
human
subjects
ingested
DMA
and
urinary
metabolites
were
measured
(
Buchet
et
al,
1981;
Marafante
et
al,
1987).

4.3.2
Toxicological
Effects
In
oral
toxicity
studies
with
DMA,
the
bladder
and
thyroid
have
been
identified
as
potential
target
organs.
As
described
below,
effects
on
the
bladder
provide
the
most
appropriate
and
toxicologically
relevant
effects
for
extrapolating
cancer
and
oral,
non­
cancer
risk
to
DMA.
In
standard
rodent
bioassays,
DMA
is
associated
with
bladder
tumors
in
female
and
male
Fischer
(
F344)
rats.
DMA
is
not
associated
with
neoplastic
responses
in
either
sex
of
B6C3F1
mice
or
two
hybrid
strains
of
mice
(
41862101;
Wei
et
al.,
1999;
NCI,
1969).
Although
negative
findings
are
found
in
the
standard
mouse
bioassay,
positive
findings
have
been
reported
in
genetically
engineered
mouse
strains
or
strains
susceptible
for
specific
tumor
types
(
Chen
et
al.,
2000;
Salim
et
al.,
2003;
Hayashi
et
al.,
1998).
Such
strains
can
be
useful
for
hazard
identification
and
may
provide
insight
into
the
chemical
and
gene
interactions
involved
in
carcinogenesis.
It
is
Page
50
of
125
inappropriate,
however,
to
use
these
strains
for
cancer
risk
extrapolation
purposes
because
they
are
engineered
to
be
highly
susceptible
to
carcinogens.

A
postulated
mode
of
action
is
a
biologically
plausible
hypothesis
for
the
sequence
of
events
leading
to
an
observed
effect
(
in
this
case,
rat
bladder
tumors).
A
mode
of
action
identifies
"
key"
cellular
and
biochemical
events 
i.
e.,
those
that
are
both
measurable
(
quantifiable)
and
critical
to
the
observed
adverse
response.
In
the
special
metabolism
and
mode
of
action
paper
on
DMA
(
USEPA
2006),
the
overall
weight
of
the
evidence
supporting
the
postulated
mode
of
action
for
DMA
is
described
in
detail.
The
Agency's
conclusions
regarding
the
mode
of
action
and
dose­
response
assessment
were
supported
by
the
SAB
at
the
September,
2005
meeting.

The
proposed
mode
of
action
for
the
development
of
bladder
tumors
from
oral
exposure
to
DMA
is
as
follows:
1)
reductive
metabolism
of
DMAV
to
DMAIII;
2)
DMAIII
causes
urothelial
cytotoxicity;
3)
regenerative
cell
proliferation
then
ensues
in
order
to
replace
dead
urothelial
cells;
4)
with
continuous
exposure,
persistent
regenerative
proliferation
leads
to
the
production
of
additional
mutations,
including
those
necessary
for
multi­
step
carcinogenesis.
As
summarized
in
Table
4.3.2a
experimental
data
are
available
to
support
the
coincidence
of
key
events
at
similar
concentration
levels.
Similarly,
time
course
data
are
available
that
support
the
sequence
of
key
events
in
time.
The
levels
of
DMAIII
in
the
urine
of
rats
treated
with
100
ppm
DMAV
range
from
0.5
 
5.0
FM.
The
LC50
values
for
DMAIII
in
rat
and
human
urinary
epithelial
cells
in
vitro
are
0.5­
0.8
FM.
There
is
a
significant
increase
in
chromosome
aberrations
in
human
lymphocytes
in
vitro
at
about
1.35
FM
DMAIII.
At
100
ppm,
there
is
significant
cell
killing
and
regenerative
proliferation
in
female
rat
bladders.
It
appears
that
chromosomal
mutations,
cytotoxicity
and
cell
proliferation
can
potentially
occur
concurrently
at
100
ppm
DMAV,
the
tumorigenic
dose
in
female
rats
via
the
feed.

The
dose­
response
relationship
for
DMA
tumorigenesis
based
on
mode
of
action
considerations
is
nonlinear
as
it
is
dependent
on
genetic,
biochemical
and
histopathological
events
for
which
dose­
response
relationships
are
nonlinear.
Page
51
of
125
Table
4.3.2a:
Summary
of
Key
Precursor
Events
and
Urinary
Bladder
Tumor
Formation
in
Female
F344
Rats
Administered
DMAV
in
the
Feed
(
Reproduced
from
USEPA
2006)

Dose
ppm
(
mg/
kg
bw/
day)
Metabolism
of
DMAV
to
DMAIII
*
Urothelial
toxicity**
Regenerative
proliferation
response***
Urothelial
hyperplasia****
Transitional
cell
carcinoma
2
(
0.2)
+
(
week
3
0.03
±
0.07uM)
+
(
week
10
6/
10,
grade
3
or
4)
­
­
­

10
(
1)
+
(
week
3
0.12
±
0.05uM)
+
(
week
3
2/
7,
grade
3)

(
week
10
8/
10,
grade
3
or
4)
+/­
(
week
10
nonstatistical
1.5­
fold
increase)
­
­

40
(
4)
+
(
week
3
0.28
±
0.24uM)
+
(
week
3
7/
7,
grade
3)

(
week
10
5/
10,
grade
3
or
4)
+
(
week
10
4.3­
fold
increase)
+
(
week
10
4/
10)
­

100
(
9.4)
+
(
week
3
0.55
±
0.4
uM)
+
(
6
hrs
6/
7,
grade
3)

(
24
hrs
4/
7,
grade
3
or
4)

(
week
2
6/
10,
grade
5)

(
week
10
10/
10,
grade
4
or
5)
+
(
week
1
2.2­
fold
increase)

(
week
2
3.9
fold)

(
week
10
4.2­
fold
increase)
+
(
week
2
1/
10)

(
week
8
7/
10)

(
week
10
9/
10)
+
(
Gur
et
al.,
1989a;
serial
sacrifices
not
performed
but
carcinoma
first
observed
at
week
87)

*
concentration
of
DMAIII
in
fresh
voided
urine
collected
from
female
rats
fed
DMAV
in
the
diet
(
Arnold
et
al.,
2004;
Cohen
et
al.,
2002a)
**
incidence
of
urothelial
toxicity
(
number
of
animals
affected
over
total
number
of
animals
examined)
and
SEM
classification
(
Arnold
et
al.,
1999;
Cohen
et
al.,
2001;
Cohen
et
al.,
2002a)
***
BrdU
labeling
index,
fold
increase
compared
to
control
value
(
Arnold
et
al.,
1999;
Cohen
et
al.,
2001)
****
Simple
hyperplasia,
number
of
animals
affected
over
total
number
of
animals
examined
(
Arnold
et
al.,
1999;
Cohen
et
al.,
2002a)
+
present
­
absent
mg/
kg
bw
per
day
estimated
by
averaging
across
studies
and
time
points.
Page
52
of
125
Thyroid
lesions,
primarily
incidence
of
cuboidal
to
columnar
epithelial
cells
lining
thyroid
follicles
were
seen
in
studies
with
the
rat
(
carcinogenicity,
subchronic,
and
two­
generation
reproduction
study).
There
is
some
evidence
that
DMA
induces
tumors
in
the
thyroid
gland
of
rats
but
at
doses
much
greater
than
those
required
to
produce
urinary
bladder
tumors.
There
is
also
some
evidence
that
DMA
has
been
used
as
a
tumor
promoter
after
initiation
of
the
thyroid
gland
with
mutagenic
chemicals
(
Yamamoto
et
al,
1995;
Yamamoto
et
al,
1997).
The
toxicological
endpoints
selected
based
on
the
bladder
tumor
mode
of
action
studies
for
DMA
are
health
protective
for
other
potential
toxicities,
including
thyroid
effects.

The
subchronic
inhalation
toxicity
study
with
DMA
indicates
that
port
of
entry
effects
of
the
nose
are
the
most
sensitive
for
inhalation
exposure.
Regarding
dermal
toxicity,
no
dermal
or
systemic
toxicity
was
noted
up
to
300
mg/
kg/
day.
At
1000
mg/
kg/
day,
the
limit
dose,
body
weight
changes
in
females
and
testicular
effects
were
noted
in
males.
The
effects
noted
in
the
testes
were
only
observed
at
the
limit
dose
and
were
not
replicated
in
other
DMA
studies.

Table
4.3.2b:
Acute
Toxicity
of
Cacodylate
3.25
(
33.3%
a.
i.)

Guideline
No.
Study
Type
MRID
#(
s)
Results
Category
870.1100
Acute
Oral
41925601
LD50
(
M&
F)
=
2800
mg/
kg
III
870.1200
Acute
Dermal
41892701
LD50
>
2000
mg/
kg
III
870.1300
Acute
Inhalation
41892702
LC50
(
4
hr):
combined
=
4.9
mg/
L;
M
=
5.8
mg/
L
&
F
=
4.0
mg/
L
IV
870.2400
Primary
Eye
Irritation
41892703
Primary
eye
irritant
­
conjunctival
redness
in
1
hr.
In
al
animals;
persisted
for
24
hrs.
In
1/
6
animals.
III
870.2500
Primary
Skin
Irritation
41892704
Negligible
irritation
in
0.5
hr.
Cleared
24
­
48
hrs.
IV
870.2600
Dermal
Sensitization
41892705
Not
a
sensitizer
N/
A
4.3.3
FQPA
Hazard
Considerations
Acceptable
developmental
studies
in
rats
and
rabbits
along
with
a
two­
generation
reproductive
toxicity
study
are
available
for
DMA.
Developmental
toxicity
was
noted
only
at
doses
resulting
in
maternal
toxicity;
NOAELs
were
established
for
maternal
and
developmental
toxicity.
As
such,
results
of
developmental
and
reproductive
toxicities
studies
provided
no
indication
of
increased
susceptibility
of
rat
or
rabbit.
Changes
in
organ
weights
for
reproductive
organs
(
e.
g.,
ovarian
weight
changes
without
pathological
changes
in
the
reproductive
toxicity
study)
and
testicular
pathology
(
dermal
study
only)
were
noted
only
at
very
high
doses
and
were
not
replicated
in
other
studies.
The
toxicology
database
is
considered
complete
for
the
evaluation
of
sensitivity
of
the
developing
young.
As
the
developing
nervous
system
does
not
appear
to
be
a
target
organ
for
DMA,
a
developmental
neurotoxicity
study
is
not
required.
Regarding
potential
Page
53
of
125
thyroid
toxicity,
a
comparative
thyroid
study
in
adult
and
juvenile
animals
is
not
expected
to
provide
endpoints
more
sensitive
than
the
bladder
mode
of
action
studies
currently
available.
The
bladder
is
a
sensitive
target
organ
and
special
mode
of
action
studies
provide
health
protective
endpoints
for
DMA
toxicity
at
low
doses.
Thus,
a
comparative
thyroid
study
in
juvenile
and
adult
animals
is
not
required.
Based
on
the
overall
weight
of
the
evidence,
the
FQPA
safety
factor
is
not
needed.

4.3.4
Dose­
Response,
Hazard
Identification
and
Toxicity
Endpoint
Selection
Toxicological
endpoints
are
needed
to
assess
potential
risk
to
DMA
from
the
following
durations
and
routes
of
exposure:

 
Acute
and
chronic
dietary
exposure,
 
Acute
­,
short­
and
intermediate­
term
incidental
oral
exposure,
 
Short­
and
intermediate­
term
dermal
exposure,
and
 
Short­
and
intermediate­
term
inhalation
exposure.

As
mentioned
above,
the
mode
of
action
for
the
development
of
bladder
tumors
in
rats
has
been
elucidated.
As
described
in
USEPA
(
2006),
this
mode
of
action
is
expected
to
be
relevant
to
humans.
The
key
steps
involved
include
conversion
of
DMAV
to
DMAIII
resulting
in
urothelial
cytotoxicity
and
the
ensuing
regenerative
proliferation
to
replace
the
dead
cells.
The
amount
of
proliferation
is
expected
to
be
a
function
of
the
amount
of
cell
killing
since
the
tissue
will
undergo
regenerative
proliferation
in
response
to
cell
killing.
As
the
severity
of
cytotoxicity
increases
with
increasing
levels
of
DMAV
(
DMAIII),
regenerative
proliferating
is
the
rate
limiting
step
for
tumor
formation.
Thus,
a
tumor
dose­
response
curve
would
be
influenced
by
the
induced
cell
proliferation
curve.
Cell
proliferation
is
not
likely
to
occur
after
a
single,
acute
exposure
but
has
been
shown
after
one
week
of
exposure.
As
such,
special
mode
of
action
data 
specifically
regenerative
cell
proliferation­­
provide
an
appropriate
endpoint
for
oral
exposure
ranging
in
duration
from
short­
term
to
chronic.

As
described
in
detail
in
EPA's
science
issue
paper,
the
Agency
performed
a
benchmark
dose
(
BMD)
analysis
of
available
data
for
key
events
leading
to
the
development
of
bladder
tumors
in
rats.
Overall,
this
analysis
was
supported
by
the
SAB.
The
SAB
did
not,
however,
support
the
use
of
a
1%
benchmark
response
(
BMR)
but
instead
suggested
a
10%
BMR
was
more
scientifically
supported
due
to
uncertainties
associated
with
extrapolating
below
the
observed
data.
Thus,
the
Agency
has
developed
its
BMD
estimates
for
regenerative
proliferation
based
on
a
10%
BMR.
BrdU
labeling
data
measured
at
10
weeks
of
DMA
exposure
in
the
feed
to
female
rats
(
Arnold
et
al,
1999)
was
used
for
the
BMD
analysis.
Using
the
Hill
model
from
EPA's
Benchmark
Dose
Software
(
BMDS),
the
results
indicate
that
the
BMD10
and
BMDL10
(
i.
e.
the
lower
95%
confidence
limit
on
the
BMD10)
are
0.92
mg/
kg/
day
and
0.43
mg/
kg/
day,
respectively.
Consistent
with
the
Agency's
draft
BMD
guidance
and
the
cancer
guidelines
(
USEPA,
2000
&
2005c),
the
point
of
departure
should
be
based
on
a
BMDL.
Therefore,
the
point
of
departure
for
the
short­
and
intermediate­
term
incidental
oral
and
the
chronic
dietary
risk
assessments
is
based
on
a
BMDL10
of
0.43
mg/
kg/
day.
Page
54
of
125
The
Agency
historically
applies
10x
uncertainty/
extrapolation
factors,
for
both
inter­
and
intraspecies
variation
(
10X
for
intra­
species;
10X
for
inter­
species).
In
the
case
of
DMA,
for
oral
exposures
ranging
from
short­
term
to
chronic
in
duration,
the
current
database
supports
reduction
of
the
default
10X
for
inter­
species
(
animal
to
human)
extrapolation
to
3X.
The
rationale
for
this
is
as
follows:
The
key
events
of
the
rat
bladder
tumor
mode
of
action
are
expected
to
be
operational
in
humans.
Based
on
the
results
of
in
vitro
studies,
it
is
further
expected
that
at
a
similar
dose
at
the
target
site
(
i.
e.
bladder
urothelial),
that
humans
and
rats
are
expected
to
respond
pharmacodynamically
similar.
Based
on
the
pharmacodynamic
characteristics,
the
default
10X
can
be
reduced
to
3X
for
DMA.
In
the
draft
report
(
December
27,
2005)
of
the
SAB,
the
panel
provides
support
for
reducing
the
default
10X
interspecies
factor
to
"
some
number
less
than
10"
and
that
the
"
EPA
could
assemble
a
case
for
toxicodynamic
equivalency
between
the
test
species,
rats,
and
humans
from
existing
experimental
data."

There
are
known
pharmacokinetic
differences
between
rats
and
humans.
These
pharmacokinetic
differences
include:
sequestration
of
DMAIII
by
rat
hemoglobin,
long
retention
time
in
the
rat
compared
to
humans
or
mice,
and
the
increased
urinary
output
of
TMAO
in
rats
compared
to
humans.
Because
of
uncertainties
regarding
quantifying
the
tissue
dose
in
humans
using
rat
data,
and
in
the
absence
of
a
fully
developed
PBPK
model,
an
inter­
species
extrapolation
factor
of
3x
will
be
applied.
The
noted
pharmacokinetic
differences
between
rats
and
humans
suggest
that
in
the
rat
that
the
target
tissue
is
likely
exposed
to
DMAIII
for
a
longer
duration
compared
to
the
human.
There
are,
however,
uncertainties
regarding
the
quantitative
differences
between
rat
and
human
which
prevents
further
reduction
of
the
inter­
species
factor.
Thus,
for
short­
and
intermediate­
term
incidental
oral
and
chronic
dietary
risk
assessment
of
DMA,
a
30X
uncertainty/
extrapolation
factor
(
10X
for
intra­
species;
3X
for
inter­
species)
has
been
applied
in
this
risk
assessment.

Regarding
acute
dietary
and
incidental
oral
exposure,
regenerative
proliferation
is
not
expected
to
occur
after
a
single
exposure.
Effects
noted
in
the
developmental
toxicity
studies
in
rat
and
rabbit
provide
an
appropriate
endpoint
for
acute
dietary
risk
assessment.
In
both
the
rat
and
rabbit
developmental
toxicity
studies,
the
maternal
and
developmental
NOAELs
are
12
mg/
kg/
day.
The
LOAELs
are
36
and
48
mg/
kg/
day,
respectively,
for
rat
and
rabbit.
As
the
effects
noted
in
the
developmental
studies
are
not
related
to
the
mode
of
action
for
bladder
tumors,
the
default
uncertainty
factor
for
inter­
species
variability
can
not
be
reduced.
A
100X
uncertainty/
extrapolation
factor
(
10X
for
intra­
species;
10X
for
inter­
species)
has
been
applied
to
the
acute
dietary
and
incidental
oral
risk
assessment.

Pharmacokinetics
of
absorption
and
metabolism
can
differ
among
oral,
dermal,
and
inhalation
exposures.
Because
of
this,
it
is
preferred
to
use
route­
specific
studies
for
risk
assessment
purposes.
Regarding
dermal
exposure,
the
DMA
dermal
toxicity
study
in
rat
indicates
a
NOAEL
of
300
mg/
kg/
day
based
on
effects
noted
at
1000
mg/
kg/
day.
Regarding
inhalation
exposures,
the
rat
inhalation
study
with
DMA
has
been
selected.
In
the
90­
day
inhalation
toxicity
study
with
DMA,
port­
of­
entry
effects,
not
systemic
ones,
are
the
most
sensitive.
A
100X
uncertainty/
extrapolation
factor
(
10X
for
intra­
species;
10X
for
inter­
species)
was
applied
to
dermal
and
inhalation
risk
assessments.
Page
55
of
125
4.3.4.1
Acute
Reference
Dose
(
aRfD)
­
General
Population
&
Acute
Incidental
Oral
Exposure
There
are
two­
co­
critical
studies
(
rat
and
rabbit
developmental
toxicity)
which
provide
the
basis
for
the
point
of
departure
for
acute
dietary
risk
assessment.

a.
In
a
developmental
toxicity
study
(
MRID#
40625701),
cacodylic
acid
(
99.8%)
was
administered
in
distilled
water
by
gavage
to
groups
of
pregnant
Charles
River
Sprague­
Dawley
rats
(
22/
dose)
at
dose
levels
of
0,
4,
12,
and
36
mg/
kg/
day
during
gestation
days
6
through
15.
The
maternal
toxicity
NOAEL
is
12
mg/
kg/
day;
the
maternal
toxicity
LOAEL
=
36
mg/
kg/
day,
based
on
decreased
body
weights,
body
weight
gains,
food
consumption
and
gravid
uterine
weights.
The
developmental
toxicity
NOAEL
is
12
mg/
kg/
day;
developmental
toxicity
LOAEL
is
36
mg/
kg/
day,
based
on
decreased
fetal
weights,
shorter
crown­
rump
length,
the
suggestion
of
diaphragmatic
hernia,
and
delayed/
lack
of
ossification
of
numerous
bones.

b.
In
a
developmental
toxicity
study
(
MRID#
40663301),
cacodylic
acid
(
99.8%,
a.
i.)
was
administered
in
water
by
oral
gavage
to
groups
of
pregnant
New
Zealand
White
rabbits
(
15/
dose)
at
dose
levels
of
0,
3,
12
or
48
mg/
kg/
day
on
gestation
days
7
through
19.
The
maternal
toxicity
NOAEL
is
12
mg/
kg/
day;
the
maternal
toxicity
LOAEL
is
48
mg/
kg/
day,
based
on
increased
mortality,
abortions,
body
weight
loss,
and
reduced
food
consumption.
The
developmental
toxicity
NOAEL
is
12
mg/
kg/
day
and
a
developmental
toxicity
LOAEL
was
not
established
since
no
pregnant
rabbit
survived
to
the
gestation
day
29
scheduled
sacrifice.

4.3.4.2
Chronic
Reference
Dose
(
cRfD)
&
Incidental
Oral
Exposure
The
Agency
performed
a
BMD
analysis
for
regenerative
proliferation
based
on
a
10%
BMR
(
USEPA
2006).
BrdU
labeling
data
measured
at
10
weeks
of
DMA
exposure
in
the
feed
to
female
rats
(
Arnold
et
al,
1999)
was
used
for
the
BMD
analysis.
Using
the
Hill
model
from
EPA's
Benchmark
Dose
Software
(
BMDS),
the
results
indicate
that
the
BMD10
and
BMDL10
(
ie,
the
lower
95%
confidence
limit
on
the
BMD10)
are
0.92
mg/
kg/
day
and
0.43
mg/
kg/
day,
respectively.
Therefore,
the
point
of
departure
for
the
short­
and
intermediate­
term
incidental
oral,
and
the
chronic
dietary
risk
assessments
is
based
on
a
BMDL10
of
0.43
mg/
kg/
day.

4.3.4.3
Dermal
Exposure
(
Short­
and
Intermediate­
Term)

In
a
21­
day
dermal
toxicity
study
(
MRID#
41872801;
HED
Doc.
No.
010410)
cacodylic
acid
(
99.95%,
a.
i.)
was
applied
dermally
under
occlusive
bandage
to
5
New
Zealand
White
rabbits/
sex/
group
at
doses
of
0,
100,
300
or
1000
mg/
kg
once
daily,
five
days
a
week
for
3
weeks.
The
systemic
toxicity
NOAEL
=
300
mg/
kg/
day;
the
LOAEL
=
1000
mg/
kg/
day,
based
on
body
weight
changes
in
females,
and
reduced
testicular
weights
and
associated
histopathological
changes
in
males.
Page
56
of
125
4.3.4.4
Inhalation
Exposure
(
Short­
and
Intermediate­
Term)

In
a
90­
day
toxicity
study
(
MRID#
44700301),
DMA
[(
Cacodylate
3.25)
(
active
ingredients:
cacodylic
acid
(
4.9%)
and
sodium
cacodylate
(
28.4%);
batch
095/
93)]
was
administered
by
inhalation
to
10
rats/
sex/
dose
at
aerosol
concentrations
of
10,
34
and
100
mg/
m3
(
analytical
concentrations
0.01,
0.034,
or
0.1
mg/
L).
The
inhalation
NOAEL
is
0.010
mg/
L/
day;
the
inhalation
LOAEL
is
0.034
mg/
L/
day
in
both
male
and
female
rats
based
on
the
presence
of
moderate
and
marked
intracytoplasmic
eosinophilic
granules
(
IEG)
in
the
cells
of
the
nasal
turbinates.

Table
4.3.4:
Summary
of
Toxicological
Doses
and
Endpoints
for
Chemical
for
Use
in
Human
Risk
Assessments
of
DMA
Exposure
Scenario
Dose
Used
in
Risk
Assessment
FQPA
SF*
and
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
Acute
Dietary
(
females
13­
49
and
general
population)
NOAEL
=
12
mg/
kg/
day
Acute
RfD
=
0.12
mg/
kg/
day
Developmental
Toxicity
­
Rat
(
40625701);
LOAEL
=
36
mg/
kg/
day
based
on
decreased
fetal
weights,
shorter
crown­
rump
length,
the
suggestion
of
diaphragmatic
hernia
and
delayed/
lack
of
ossification
of
numerous
bones.
Developmental
Toxicity
­
Rabbit
(
40663301);
LOAEL
=
48
mg/
kg/
day
based
on
mortality,
abortions,
body
weight
loss
and
reduced
food
consumption.

Chronic
Dietary
(
all
populations)
BMDL10
=
0.43
mg/
kg/
day
Chronic
RfD
=
0.014
mg/
kg/
day
BMD10
of
0.92
mg/
kg/
day
for
BrdU
labeling
from
Arnold
et
al
(
1999)

Incidental
Oral
Acute­
Term
(
1
day)
NOAEL
=
12
mg/
kg/
day
LOC
=
100
Developmental
Toxicity
­
Rat
(
40625701);
LOAEL
=
36
mg/
kg/
day
based
on
decreased
fetal
weights,
shorter
crown­
rump
length,
the
suggestion
of
diaphragmatic
hernia
and
delayed/
lack
of
ossification
of
numerous
bones.
Developmental
Toxicity
­
Rabbit
(
40663301);
LOAEL
=
48
mg/
kg/
day
based
on
mortality,
abortions,
body
weight
loss
and
reduced
food
consumption.

Incidental
Oral
Short­
Term
(
1
­
30
days)

Intermediate­
Term
(
1
­
6
months)
BMDL10
=
0.43
mg/
kg/
day
LOC
=
30
BMD10
of
0.92
mg/
kg/
day
for
BrdU
labeling
from
Arnold
et
al
(
1999)

Dermal
Short­
Term
(
1
­
30
days)

Intermediate­
Term
(
1
­
6
months)
Dermal
NOAEL=
300
mg/
kg/
day
LOC
=
100
21­
Day
Dermal
­
Rabbit
(
41872801);
LOAEL
=
1000
mg/
kg/
day
based
on
decreased
body
weight
gain
in
females,
and
decreased
testicular
weights,
hypospermia,
and
tubular
hypoplasia
in
males.

Dermal
Long­
Term
(>
6
months)
Not
required
Inhalation
Short­
Term
(
1
­
30
days)

Intermediate­
Term
(
1
­
6
months)
Inhalation
NOAEL=
0.01
mg/
L
(
4.38
mg/
kg/
day)
LOC
=
100
90­
Day
Inhalation
­
Rat
(
44700301);
LOAEL
=
0.034
mg/
kg/
L
(
14.95
mg/
kg/
day)
based
on
presence
of
moderate
and
marked
intracytoplasmic
eosinophilic
granules
(
IEG)
in
the
nasal
turbinate
cells
of
male
and
female
rats.

Inhalation
Long­
Term
(>
6
months)
Not
required
Cancer
(
oral)
Not
carcinogenic
at
doses
that
do
not
result
in
enhanced
cell
proliferation
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
Page
57
of
125
4.3.5
Recommendation
for
Aggregate
Exposure
Risk
Assessments
The
FQPA
(
1996)
requires
that
EPA
aggregate
risks
from
multiple
pathways
as
part
of
tolerance
reassessment.
OPP
aggregates
risk
from
multiple
pathways
and
routes
in
cases
where
the
toxic
effect
of
interest
is
common
among
or
between
the
routes
of
interest.
In
the
case
of
DMA,
exposures
from
the
oral
route
(
food,
water,
incidental
oral)
may
be
aggregated.
The
bladder
was
not
noted
as
a
target
organ
in
the
dermal
or
the
inhalation
toxicity
studies.
As
such,
it
is
inappropriate
to
aggregate
risks
from
dermal
and
inhalation
exposures.

4.3.6
Classification
of
Carcinogenic
Potential
As
described
in
the
special
issue
paper
for
DMA,
the
mode
of
action
for
the
development
of
bladder
tumors
in
rats
has
been
established
and
supports
a
nonlinear
dose­
response
assessment.
This
mode
of
action
is
expected
to
be
functional
in
humans.
A
key
step
in
this
mode
of
action
is
that
sufficient
DMAIII
is
available
at
the
target
site
to
cause
cell
killing.
This
cytotoxicity
must
be
sustained
to
result
in
regenerative
proliferation.
Each
of
these
key
steps
is
necessary
for
the
development
of
bladder
tumors.
Based
on
EPA's
2005
(
USEPA
2005b)
cancer
guidelines,
DMA
is
considered
"
not
likely
to
be
carcinogenic
to
humans
at
doses
that
do
not
result
in
enhanced
cell
proliferation"

4.3.7
Endocrine
Disruption
EPA
is
required
under
the
FFDCA,
as
amended
by
FQPA,
to
develop
a
screening
program
to
determine
whether
certain
substances
(
including
all
pesticide
active
and
other
ingredients)
"
may
have
an
effect
in
humans
that
is
similar
to
an
effect
produced
by
a
naturally
occurring
estrogen,
or
other
such
endocrine
effects
as
the
Administrator
may
designate."
Following
recommendations
of
its
Endocrine
Disruptor
and
Testing
Advisory
Committee
(
EDSTAC),
EPA
determined
that
there
was
a
scientific
basis
for
including,
as
part
of
the
program,
the
androgen
and
thyroid
hormone
systems,
in
addition
to
the
estrogen
hormone
system.
EPA
also
adopted
EDSTAC's
recommendation
that
the
Program
include
evaluations
of
potential
effects
in
wildlife.
For
pesticide
chemicals,
EPA
will
use
FIFRA
and,
to
the
extent
that
effects
in
wildlife
may
help
determine
whether
a
substance
may
have
an
effect
in
humans,
FFDCA
authority
to
require
the
wildlife
evaluations.
As
the
science
develops
and
resources
allow,
screening
of
additional
hormone
systems
may
be
added
to
the
Endocrine
Disruptor
Screening
Program
(
EDSP).
Limited
changes
in
organ
weights
for
reproductive
organs
(
e.
g.
ovarian
weight
changes
without
pathological
changes
in
the
reproductive
toxicity
study)
and
testicular
pathology
(
dermal
study
only)
were
noted
only
at
very
high
doses
with
DMA.
These
effects
were
not
replicated
in
other
studies.
Regarding
potential
thyroid
toxicity,
the
changes
in
thyroid
follicular
cell
height
do
not
progress
to
longer
term
health
outcomes.
The
bladder
is
a
sensitive
target
organ
and
special
mode
of
action
studies
provide
health
protective
endpoints
for
DMA
toxicity
at
low
doses.
Page
58
of
125
5.0
Public
Health
Data
5.1
Incident
Reports
OPP
draws
from
4
different
databases
to
determine
what,
if
any,
poisoning
incidents
have
occurred
that
can
be
related
to
pesticidal/
herbicidal
use.
A
summary
of
the
databases
follows.

1)
Office
of
Pesticide
Program's
Incident
Data
System
(
IDS)
­
includes
reports
of
incidents
from
various
sources,
including
required
Federal
Insecticide
Fungicide
and
Rodenticide
Act
(
FIFRA)
Section
6
(
a)
(
2)
registrants,
other
federal
and
state
health
and
environmental
agencies
and
individual
consumers,
submitted
to
the
Agency
since
1992.
Reports
submitted
to
the
IDS
represent
anecdotal
reports
or
allegations
only,
unless
otherwise
stated.
Typically
no
conclusions
can
be
drawn
implicating
the
pesticide
as
a
cause
of
any
of
the
reported
health
effects.
Nevertheless,
sometimes
with
enough
cases
and/
or
enough
documentation
risk
mitigation
measures
may
be
suggested.

2)
American
Association
of
Poison
Control
Centers
(
AAPCC)
­
as
the
result
of
Data­
Call­
Ins
issued
in
1993,
the
Agency
received
Poison
Control
Center
data
covering
the
years
1985
through
1992
for
28
organophosphate
and
carbamate
chemicals.
Most
of
the
national
Poison
Control
Centers
(
PCCs)
participate
in
a
national
data
collection
system,
the
Toxic
Exposure
Surveillance
System
which
obtains
data
from
about
70
centers
at
hospitals
and
universities.
PCCs
provide
telephone
consultation
for
individuals
and
health
care
providers
on
suspected
poisonings
involving
drugs,
household
products,
pesticides,
etc.

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

4)
National
Pesticide
Telecommunications
Network
(
NPTN)
­
NPTN
is
a
toll­
free
information
service
supported
by
the
Agency's
Office
of
Pesticide
Programs.
A
ranking
of
the
top
200
active
ingredients
for
which
telephone
calls
were
received
during
calendar
years
1984­
1991,
inclusive
has
been
prepared.
The
total
number
of
calls
was
tabulated
for
the
categories;
human
incidents,
animal
incidents,
calls
for
information,
and
others.

5.1.1
Cacodylic
Acid
Incidents
For
the
purposes
of
this
assessment
the
focus
was
on
those
human
incidents
that
are
directly,
or
probably,
related
to
exposures
to
cacodylic
acid
or
sodium
cacodylate
per
se.
Drawing
from
four
data
sources,
there
were
reported
poisoning
incidents
involving
children
<
6
years
of
age,
but
none
were
hospitalized,
and
no
specifics
were
given
about
the
activity
associated
with
the
exposures.
Incidents
reported
for
adults
involved
both
agricultural
and
non­
agricultural
uses,
and
resulted
in
days
off
from
work
and,
in
a
few
cases,
hospitalization.
The
symptoms
ranged
from
systemic,
to
skin
and
eye
irritation,
to
respiratory
system
effects.
Some
cases
involved
multiple
Page
59
of
125
symptoms.
The
uses
included
lawn,
turf,
ornamentals,
weeds,
and
cotton.
For
more
details
see
Allen
2000a.

5.1.2
MSMA/
DSMA
Incidents
HED
searched
the
four
databases
discussed
above
for
reports
of
incidents
occurring
resulting
from
exposures
to
MSMA
or
DSMA.
There
were
incidents
reported
for
both
MSMA
and
DSMA,
involving
both
adults
and
children.
Most
were
treated
on
an
outpatient
basis
but
a
few
required
hospitalizations.
Some
reports
described
symptoms
such
as
dizziness,
sinusitis,
rhinitis,
memory
loss,
numbness,
tingling,
rash,
and
fever,
after
aerial
applications,
but
many
were
nonspecific
about
the
source
of
exposure.
Other
reports
described
effects
such
as
systemic
allergic
symptoms,
nausea,
dizziness,
and
eye
irritation
for
both
agricultural
and
non­
agricultural
uses.
Specific
details
may
be
found
in
Allen
2000b.

There
are
only
scattered
reports
for
MSMA/
DSMA
among
the
four
data
systems
used
by
the
Agency's
epidemiology
group
to
evaluate
human
poisoning
incidents.
The
sparsity
of
data
could
be
due
to
low
usage,
and/
or
poor
reporting
to
surveillance
programs.
From
the
limited
information
available,
systemic
allergic
reactions
and
eye
irritation
are
possible
targets
for
preventive
intervention.

5.1.3
CAMA
Incidents
HED
searched
the
same
four
databases
for
evidence
of
poisoning
incidents
connected
with
the
use
of
CAMA
and
found
none.
Currently,
CAMA
has
no
agricultural
uses.
See
Allen
2001.

5.2
Other
No
scientific
literature
pertinent
to
additional
health
effects
of
the
organic
arsenicals
in
humans
was
located.

6.0
Exposure
Characterization/
Assessment
6.1
Dietary
Exposure/
Risk
Pathway
Arsenic
speciation
in
the
environment
is
complex,
and
exists
in
both
inorganic
and
organic
forms
with
interconversion
between
species
depending
on
varying
conditions
within
the
soil
(
i.
e.,
phosphorus
levels
in
the
soil,
pH,
microbial
environment,
etc.).
When
determining
residue
values
for
arsenic
in
food
and
drinking
water,
it
is
important
to
understand
how
arsenic
is
taken
up
from
the
soil
by
the
roots
and
metabolized
within
plants.
In
plant
metabolism,
limited
evidence
suggests
that
plants
may
metabolize
iAs
through
biomethylation
to
MMA,
DMA,
tetramethylarsonium
ions
(
TETRA)
and
trimethylarsonium
oxide
(
TMAO),
and
further
metabolize
to
arsenocholine,
arsenobetaine,
and
arsenosugars.
However,
it
has
not
been
proven
whether
these
compounds
are
products
of
plant
metabolism
or
if
they
are
simply
taken
up
from
the
soil
in
those
forms.
To
further
complicate
the
residue
picture,
metabolism
is
also
dependant
on
a
number
of
other
factors,
such
as
the
plant's
ability
to
uptake
the
compounds,
the
plant's
ability
to
synthesize
arsenic
species
(
some
plants
may
have
arsenic
resistance
due
to
evolution),
Page
60
of
125
and
the
presence
of
arsenic
species
adsorbed
to
the
outside
surface
of
the
plant
roots.
Therefore,
determining
residues
of
arsenic
in
food
and
drinking
water
is
extremely
complex.
There
are
insufficient
data
at
this
time
to
determine
specific
amounts
of
the
various
arsenic
compounds
in
plants
on
a
national
level
since
the
background
levels
are
highly
variable
and
speciation
is
dependent
on
so
many
different
factors,
all
of
which
are
present
in
a
given
environment.
Human
and
other
mammal
metabolism
of
arsenic
is
also
variable
and
complex
(
see
section
3.0).

6.1.1
Residue
Profile
Cacodylic
Acid
Use:
Cacodylic
acid
and
its
salt
are
nonselective,
contact
herbicides.
The
only
food/
feed
use
of
cacodylic
acid
is
as
a
defoliant
on
cotton.
All
registered
cacodylic
acid
MPs
and
EPs,
registered
for
use
on
cotton,
contain
cacodylic
acid
and
its
sodium
salt
in
combination
at
a
ratio
of
approximately
1:
6
(
wt:
wt).
The
most
recent
Screening
Level
Usage
Analysis
(
SLUA)
report
from
the
Biological
and
Economic
Analysis
Division
(
BEAD)
indicates
that
the
largest
market
for
cacodylic
acid
is
on
cotton.
Nationwide,
<
2.5%
of
cotton
acreage
is
treated
with
cacodylic
acid
(
Carter
2005a,
b,
c,
d).

The
tolerance
currently
established
for
residues
of
cacodylic
acid,
expressed
as
As2O3,
in/
on
cottonseed
is
2.8
ppm
(
40
CFR
§
180.311).
Tolerances
for
residues
of
DMA
in/
on
meat,
milk,
poultry,
and
eggs
(
MMPE)
were
revoked
in
2004
(
40
CFR
Part
180
[
OPP­
2003­
0344;
FRL­
7338­
3]
Aldicarb,
Atrazine,
Cacodylic
Acid,
Carbofuran,
et
al.;
Tolerance
Actions.
Federal
Register/
Vol.
69,
No.
28/
Wednesday,
February
11,
2004/
Rules
and
Regulations,
pp.
6561­
6567)
due
to
no
expectation
of
finite
residues
in
these
commodities.
If
warranted,
this
may
be
revisited
in
the
future.
There
are
no
Codex
maximum
residue
levels
(
MRL)
established
for
cacodylic
acid.

The
qualitative
nature
of
the
residue
for
cacodylic
acid
and
its
sodium
salt
in
plants
and
animals
is
adequately
understood,
but
uncertainties
remain.
Based
on
the
available
data
and
published
information,
the
Metabolism
Committee
concluded
that
the
only
residue
of
concern
is
cacodylic
acid
per
se
(
Swartz
1995).
This
decision
was
predicated
on
evidence
available
at
the
time
that
little
or
no
demethylation
of
cacodylic
acid
is
likely
to
occur
in/
on
cotton
and
animal
commodities.
It
should
be
noted
however,
that
additional
data
for
plant
residue
analytical
methods
and
ILV
requirements
to
support
the
reregistration
of
cacodylic
acid
and
its
sodium
salt
are
currently
under
review
[
MRID#
459366­
01
(
03/
04/
2003)
and
MRID#
459366­
02
(
04/
10/
2002)].
In
addition,
unspeciated
monitoring
data,
show
measurable
levels
of
total
arsenic
on
food
crops
for
which
there
are
no
registrations,
including
meat
and
milk,
and
it
is
unknown
at
this
time
how
plants
up
take
residues
from
contaminated
soils
and
subsequently
metabolize
them.
It
is
also
unknown
what
species
(
MMA,
DMA,
or
iAs)
may
be
present
on
these
foodstuffs.

DSMA
&
MSMA
Use:
MMA
and
its
salts
are
selective
pre­
and
post­
emergence
organic
arsenical
herbicides
registered
for
use
for
weed
control.
Tolerances
have
been
established
[
40
CFR
§
180.289(
a)]
for
residues
of
MMA,
calculated
as
arsenic
trioxide
(
As2O3),
resulting
from
applications
of
the
disodium
and
monosodium
salts
in/
on
citrus
fruit
(
0.35
ppm),
cottonseed
(
0.7
ppm),
and
cottonseed
hulls
(
0.9
ppm).
Note
 
Bearing
citrus
use
is
no
longer
being
supported.
DMA
is
a
MSMA/
DSMA
Page
61
of
125
transformation
product
of
concern,
and
was
found
in
cotton
and
citrus
raw
agricultural
commodities
(
RACs)
treated
with
MSMA
and/
or
DSMA.
Tolerances
have
been
established
[
40
CFR
§
180.311]
for
residues
of
the
DMA,
also
expressed
as
As2O3,
in/
on
cottonseed
(
2.8
ppm).
According
to
40
CFR
§
180.3(
d)(
4),
where
a
tolerance
is
established
for
more
than
one
pesticide
containing
arsenic
found
in/
on
a
RAC,
the
total
amount
of
such
pesticide
shall
not
exceed
the
highest
established
tolerance,
calculated
as
As2O3.
There
are
no
established
Codex
Maximum
Residue
Levels
(
MRLs)
for
MMA.
Therefore,
issues
of
Codex
harmonization
do
not
exist.

The
qualitative
nature
of
the
residue
for
DSMA,
MSMA,
and
its
transformation
product,
DMA,
in
plants
is
adequately
understood,
but
uncertainties
remain.
Based
on
available
data
and
published
information,
the
HED
Metabolism
Committee
concluded
that
the
residue
of
concern
associated
with
the
use
of
MSMA
and
DSMA,
are
MSMA
and
cacodylic
acid
(
Swartz
1995).
This
conclusion
was
based
on
evidence
available
at
the
time
concerning
a
low
rate
or
lack
of
demethylation,
and
on
the
inability
of
the
current
enforcement
method
to
distinguish
between
background
arsenic
and
arsenic
resulting
from
herbicidal
use.
The
HED
Metabolism
Committee
(
Swartz
1995)
also
concluded
that
there
was
no
reasonable
expectation
of
finite
residues
of
concern
in
meat,
milk,
poultry,
and
eggs
as
a
result
of
registered
uses;
that
is,
residues
in
meat,
milk,
poultry,
and
eggs
can
be
classified
under
Category
3
of
CFR
§
180.6(
a).
Tolerances
and
feeding
studies
are
not
required
at
this
time.
However,
if
warranted,
this
may
be
revisited
in
the
future.
Speciated
monitoring
data
are
needed.

Co­
occurrence:
Known
agricultural
practices
with
organic
arsenics
on
cotton
(
source
of
cottonseed
commodities),
for
example,
increase
the
likelihood
that
one
might
be
exposed
to
co­
occurring
residues
of
DMA
from
applications
of
DMA
and
MMA
salts.
There
is
potential
for
cooccurrence
of
DSMA
or
MSMA,
and
cacodylic
acid
from
sequential
treatments
on
cotton
but
cooccurrence
from
simultaneous
use
appears
to
be
unlikely.
DSMA
and
MSMA
are
used
as
earlyseason
directed­
spray
herbicides
on
cotton;
cacodylic
acid
is
used
to
defoliate
cotton
late
in
the
growing
season
before
harvest
(
Carter
2006).
Additional
dietary
sources
of
DMA
and
MMA
residues
may
come
from
other
food
commodities
(
background)
and
from
drinking
water.
Since
the
percent
crop
treated
(%
CT)
for
the
MMA
salts
(
Carter
2005e,
f/
Dobbins
2005a,
b,
c)
and
DMA
are
<
20%
and
<
2.5%
CT
on
cotton
respectively,
co­
occurring
residues
of
DMA
or
MMA
would
not
be
expected
to
occur
on
more
than
2.5%
of
the
crop
treated
with
the
organic
arsenicals;
however,
<
1%
co­
occurrence
of
both
residues
is
expected.
Based
on
the
submitted
data
and
very
limited
speciation
information,
the
residues
on
cottonseed
resulting
from
the
herbicidal
uses
would
be
expected
to
be
primarily
organic
arsenic.
Uptake
of
background
residues
in
soils,
depending
on
a
variety
of
environmental
conditions,
may
be
a
combination
of
organic
and
iAs
species.

Rotational
Crops:
When
assessing
the
herbicidal
uses
of
the
organic
arsenicals,
one
must
consider
that
what
is
applied
(
registered
uses)
will
contribute
to
background
levels
of
arsenic
over
time.
Therefore,
over
years
of
applications
of
the
organic
arsenical
herbicides,
background
levels
tend
to
increase
and
the
arsenic
species
present
interconvert
between
species
depending
on
varying
environmental
conditions
within
the
soil
(
i.
e.,
pH,
microbial
environment,
etc.).
Therefore,
this
constant
contribution
of
arsenic
could
cause
higher
residues
to
be
found
not
only
in
the
registered
Page
62
of
125
crop,
but
also
in
crops
that
are
rotated.
This
may
explain
why
the
FDA
TDS
shows
detectable
residues
in
cereal
grains
more
frequently
than
other
crops
since
cereal
grains
are
often
rotated
with
cotton.
Both
cotton
and
cereal
grains
are
also
livestock
feed
commodities.
Increased
arsenic
levels
in
the
portions
of
cotton
and
cereal
grains
that
are
fed
to
livestock
can
result
in
an
increase
of
arsenic
residues
in
the
edible
tissues,
thus
increasing
dietary
exposure
to
arsenic.
The
FDA
TDS
has
also
found
detectable
residues
of
arsenic
in
the
edible
tissues
of
livestock
(
mostly
beef
liver)
as
well
as
poultry.
However,
the
detectable
residues
found
in
poultry
meat
are
most
likely
due
to
arsenic
use
as
a
growth
promoter
in
poultry
and
swine
(
FDA
tolerances
for
chicken,
turkey,
and
swine
are
listed
under
21
CFR
556.60).
These
uses
also
contribute
to
the
dietary
exposure
to
arsenic.

FDA
Total
Diet
Study:
Determining
residues
of
arsenic
in
food
and
drinking
water
is
extremely
complex.
There
are
insufficient
data
at
this
time
to
determine
specific
amounts
of
the
various
arsenic
compounds
in
plants
since
the
levels
are
dependent
on
so
many
different
factors,
all
of
which
could
be
present
in
any
given
environment.
The
best
available
data
to
capture
the
total
amount
of
arsenic
in
food
commodities
on
a
national
level
are
the
FDA
TDS.
However,
though
the
data
provided
by
the
TDS
are
the
best
available
data
at
this
time,
they
are
limited
and
are
not
designed
for
use
in
dietary
exposure
assessments.
The
commodities
that
were
tested
in
the
FDA
TDS,
though
some
RAC
data
are
provided,
are
predominantly
the
processed
and
cooked
commodities
as
eaten.
Another
limitation
of
using
the
FDA
TDS
data
for
a
dietary
assessment
of
organic
or
inorganic
arsenic
in
food
is
that
the
method
used
for
quantifying
residues
of
arsenic
in
the
study
does
not
speciate;
therefore,
HED
cannot
determine
how
much
of
the
total
residues
are
inorganic
versus
organic
arsenic.
These
factors
contribute
uncertainty
and
possible
conservativeness,
due
to
lack
of
speciation,
to
the
assessment.

Residue
Data
Used
for
the
Acute
and
Chronic
Dietary
Assessments:
For
both
acute
and
chronic
total
organic
arsenic
assessments,
field
trial
data
combined
with
%
CT
estimates
from
BEAD
(
Carter
2005a,
b,
c,
d,
e,
f)
were
used
for
cotton,
and
the
FDA
Total
Diet
Study
(
TDS)
data
were
used
directly
in
residue
distribution
files
for
all
other
commodities.
HED
notes
that
this
may
be
an
overestimation
since
it
is
assumed
that
there
is
a
small
amount
of
arsenic
in
all
the
commodities
that
were
included.
As
mentioned
above,
the
commodities
that
were
tested
are
predominantly
the
processed
and
cooked
commodities
as
eaten.
Therefore,
some
non­
standard
assumptions
were
used.
For
example,
for
almonds,
the
data
that
were
used
from
the
TDS
are
for
mixed
nuts,
no
peanuts,
dry
roasted.
It
was
assumed
that
the
residues
found
on
the
mixed
nuts
are
representative
of
residues
that
one
would
expect
to
see
on
almonds.
These
types
of
assumptions
were
used
throughout
the
assessment.
Default
processing
factors
were
used
unless
there
were
data
on
the
processed
commodities,
and
then
that
data
were
used
directly
with
no
additional
adjustments.
Please
refer
to
the
dietary
memo
(
Kinard
2006)
for
details
on
how
the
data
were
translated
and
used.

6.1.2
Dietary
Risk
Assessment/
Characterization
Acute
and
chronic
dietary
risk
assessments
for
DMA
and
MMA
resulting
from
food/
feed
uses
of
cacodylic
acid
and
salts,
DSMA,
and
MSMA
were
conducted
using
the
Dietary
Exposure
Evaluation
Model
(
DEEM­
FCID
 
,
Version
2.03)
which
uses
food
consumption
data
from
the
Page
63
of
125
USDA's
Continuing
Surveys
of
Food
Intakes
by
Individuals
(
CSFII)
from
1994­
1996
and
1998.
Consumption
data
are
averaged
for
the
entire
U.
S.
population
and
within
various
population
subgroups
to
conduct
chronic
and
cancer
risk
estimates,
but
retained
as
individual
daily
consumption
data
points
to
conduct
acute
risk
estimates
(
which
are
based
on
distributions
of
consumption
estimates
for
either
deterministic
or
probabilistic
type
exposure
estimates).
The
analyses
were
performed
to
support
the
reregistration
eligibility
decisions
for
cacodylic
acid,
DSMA,
and
MSMA.

Cacodylic
acid
is
a
registered
herbicide
as
well
as
a
common
transformation
product
of
DSMA,
MSMA,
and
CAMA.
The
only
registered
use
of
cacodylic
acid
in/
on
a
food/
feed
crop
is
cottonseed,
and
the
only
registered
uses
of
DSMA
and
MSMA
in/
on
food/
feed
crops
are
citrus
and
cottonseed
commodities;
however,
the
bearing
citrus
use
is
no
longer
being
supported;
therefore,
citrus
was
not
included
as
a
registered
use.
There
are
currently
no
registered
uses
of
CAMA
in/
on
food/
feed
crops;
therefore,
it
is
not
included
in
the
dietary
assessment.

Under
the
Food
Quality
Protection
Act
(
FQPA),
the
acute
and
chronic
dietary
exposure
and
risk
estimates
cannot
be
limited
to
residues
of
DMA
and
MMA
and
their
salts
on
cotton
seed
but,
must
include
all
sources
of
dietary
exposure.
Arsenic
residues
incurred
in/
on
food
from
other
potential
sources
of
arsenic,
including
background
levels,
have
been
included.
No
monitoring
data
for
residues
of
DMA
or
MMA
per
se
are
available
from
FDA
and/
or
USDA.
The
available
monitoring
data
on
total
arsenic
(
as
As2O3)
from
the
FDA
TDS
(
Market
Baskets
91­
3
through
7­

1)
are
limited
for
the
food/
food­
forms
of
concern
and
are
likely
to
significantly
overestimate
dietary
exposure
to
arsenic
from
agricultural
applications
of
DMA
and
MMA.
The
FDA
TDS
includes
residues
of
arsenic
from
all
potential
sources
including
background
and
are
the
best
available
data
at
this
time
for
assessing
dietary
risk
on
a
national
level.
The
anticipated
residue
estimates
are
considered
moderately
refined,
although
are
considered
conservative
based
on
assumptions
that
were
made
due
to
the
lack
of
arsenic
speciated
data.
Such
anticipated
residue
estimates
are
likely
to
overestimate
the
dietary
exposure
and
risk
from
the
combined
agricultural
herbicidal
use
of
cacodylic
acid,
DSMA,
and
MSMA.

6.1.2.1
Acute
Dietary
Exposure
Results
and
Characterization
Several
acute
dietary
assessments
were
performed
for
the
organic
arsenicals
using
field
trial
data,
FDA's
TDS
data,
%
CT
information,
and
default
processing
factors.
Since
arsenic
is
ubiquitous
in
the
environment
and
was
quantified
as
total
arsenic
in
the
best
available
data,
it
was
not
possible
to
determine
where
the
arsenic
originated
from
(
i.
e.,
background
or
from
herbicidal
use)
or
to
determine
speciated
residue
values
for
use
in
a
national
dietary
exposure
assessment;
therefore,
these
assessments
contain
assumptions
that
are
not
standard
for
HED
dietary
exposure
assessments.
A
number
of
the
assumptions
that
have
been
made
in
these
assessments
are
considered
to
be
conservative.
However,
when
assuming
that
all
arsenic
found
in
the
field
trials,
reported
in
the
FDA
TDS,
and
estimated
in
drinking
water
is
either
MMA
or
DMA,
risks
are
below
HED's
level
of
concern
for
the
U.
S.
population
and
all
population
subgroups
at
the
99.9th
percentile
of
exposure.
Commodities
that
contributed
the
most
to
the
acute
dietary
assessments
are
fish
and
drinking
water.
Page
64
of
125
6.1.2.2
Chronic
Dietary
Exposure
Results
and
Characterization
Several
chronic
dietary
assessments
were
also
performed
for
the
organic
arsenicals
using
field
trial
data,
FDA's
TDS
data,
%
CT
information,
and
default
processing
factors.
As
above
(
6.1.2.1),
a
number
of
the
assumptions
that
have
been
made
in
these
assessments
are
considered
to
be
conservative.
However,
when
assuming
that
all
arsenic
found
in
the
field
trials,
reported
in
the
FDA
TDS,
and
estimated
in
drinking
water
is
either
MMA
or
DMA,
risks
are
below
HED's
level
of
concern
for
the
U.
S.
population
and
all
population
subgroups.
Commodities
that
contributed
the
most
to
the
chronic
dietary
assessments
are
rice
and
cereal
grains.

MMA,
or
its
sodium
or
calcium
salts,
have
been
classified
as
"
not
likely"
human
carcinogens,
and
DMA
is
considered
not
carcinogenic
up
to
doses
resulting
in
regenerative
proliferation;
therefore,
separate
cancer
assessments
for
MMA
and
DMA
have
not
been
performed.

6.1.2.3
Dietary
Risk
Results/
Discussion
For
acute
and
chronic
assessments,
HED
is
concerned
when
dietary
risk
exceeds
100%
of
the
population
adjusted
dose
(
PAD).
The
DEEM­
FCID
 
analyses
estimate
the
dietary
exposure
of
the
U.
S.
population
and
various
population
subgroups.
The
dietary
(
food
and
water)
risk
assessment
was
conducted
in
a
stepwise
fashion.
The
results
presented
here
show
the
bounding
ends
(
Level
1
&
3)
of
the
range
of
potential
risks,
but
more
details
can
be
found
in
Kinard
2006.
For
all
scenarios,
drinking
water
estimates
provided
by
EFED
for
both
runoff
from
applications
to
cotton
and
applications
to
turf
were
included.
All
species
of
concern
in
this
assessment
(
MMA,
DMA,
and
iAs)
have
distinct
toxicities;
exposures
to
each
are
considered
individually.
More
discussion
on
potential
risks
from
iAs
exposure
can
be
found
in
Section
7.7.

Level
1:
Acute
and
chronic
dietary
exposure
analyses
include
only
the
registered
food
commodity,
cottonseed
(
field
trial
data
resulting
from
the
max
application
of
DSMA/
MSMA
and
cacodylic
acid
to
cotton
grown
in
non­
arsenic
containing
soil),
and
two
different
drinking
water
scenarios
(
cotton
and
turf).

Level
2:
Acute
and
chronic
dietary
exposure
analyses
include:
a)
cottonseed
and
meat
(
residue
estimates
from
FDA
TDS);
b)
cottonseed,
meat,
and
two
different
drinking
water
scenarios;
c)
cottonseed,
meat,
and
fish
(
residue
estimates
also
from
FDA
TDS);
and,
d)
cottonseed,
meat,
fish,
and
two
different
water
scenarios
(
details
can
be
found
in
Kinard
2006).

Level
3:
Acute
and
chronic
dietary
exposure
analyses
include:
a)
cottonseed
and
all
commodities
that
were
tested
in
the
FDA
TDS;
b)
cottonseed,
all
commodities
that
were
tested
in
the
FDA
TDS
and
two
different
drinking
water
scenarios;
c)
cottonseed,
all
commodities
that
were
tested
in
the
FDA
TDS,
as
well
as
all
commodities
for
which
translations
could
be
made
from
the
TDS
data;
and,
d)
cottonseed,
all
commodities
that
were
tested
in
the
FDA
TDS,
all
translated
commodities,
and
two
different
drinking
water
scenarios.
Page
65
of
125
Results
of
Level
1
Acute
and
Chronic
Dietary
Exposure
Analysis
The
acute
results
listed
below
assume
100%
of
the
total
arsenic
concentration
is
either
MMA
(
Table
6.1.2.3a)
or
DMA
(
Table
6.1.2.3b).
The
acute
dietary
risk
estimates
at
the
99.9th
percentile
for
food
exposure
to
MMA
are
not
of
concern
for
the
U.
S.
population
and
all
population
subgroups,
nor
are
the
acute
risk
estimates
of
concern
for
the
food
and
water
aggregate
exposure
to
MMA.
Similarly,
the
acute
dietary
risk
estimates
at
the
99.9th
percentile
for
food
exposure
and
the
food
and
water
aggregate
exposure
to
DMA
are
not
of
concern
for
the
U.
S.
population
and
all
population
subgroups.

Table
6.1.2.3a:
Acute
Dietary
Risk
Results
at
the
99.9th
%
tile
of
Exposure
from
the
Cotton
Use
for
the
Organic
Arsenical
Herbicides
Using
DEEM
FCID
with
the
MMA
aPAD
of
0.1
mg/
kg/
day
Food
only
Food
+
Cotton
Water
Food
+
Turf
Water
Population
Subgroup
Exposure
(
mg/
kg/
day)
%
aPAD
Exposure
(
mg/
kg/
day)
%
aPAD
Exposure
(
mg/
kg/
day)
%
aPAD
U.
S.
Population
0.000018
<
1
0.002229
2.2
0.021484
21.5
All
Infants
(<
1
yr.)
0.000009
<
1
0.007081
7.1
0.061812
61.8
Children
1­
2
yrs.
0.000029
<
1
0.003145
3.1
0.028373
28.4
Children
3­
5
yrs.
0.000040
<
1
0.002820
2.8
0.025179
25.2
Children
6­
12
yrs.
0.000019
<
1
0.001973
2.0
0.017495
17.5
Youth
13­
19
yrs.
0.000016
<
1
0.001709
1.7
0.016117
16.1
Adults
20­
49
yrs.
0.000014
<
1
0.001911
1.9
0.017530
17.5
Adults
50+
yrs.
0.000006
<
1
0.001592
1.6
0.013899
13.9
Females
13­
49
yrs.
0.000014
<
1
0.001890
1.9
0.017253
17.2
Table
6.1.2.3b:
Acute
Dietary
Risk
Results
at
the
99.9th
%
tile
of
Exposure
from
the
Cotton
Use
for
the
Organic
Arsenical
Herbicides
Using
DEEM
FCID
with
the
DMA
aPAD
of
0.12
mg/
kg/
day
Food
only
Food
+
Cotton
Water
Food
+
Turf
Water
Population
Subgroup
Exposure
(
mg/
kg/
day)
%
aPAD
Exposure
(
mg/
kg/
day)
%
aPAD
Exposure
(
mg/
kg/
day)
%
aPAD
U.
S.
Population
0.000018
<
1
0.003347
2.8
0.014430
12.0
All
Infants
(<
1
yr.)
0.000009
<
1
0.008155
6.8
0.036330
30.3
Children
1­
2
yrs.
0.000029
<
1
0.003763
3.1
0.016023
13.4
Children
3­
5
yrs.
0.000040
<
1
0.003392
2.8
0.016081
13.4
Children
6­
12
yrs.
0.000019
<
1
0.002265
1.9
0.009701
8.1
Youth
13­
19
yrs.
0.000016
<
1
0.002426
2.0
0.011225
9.4
Adults
20­
49
yrs.
0.000014
<
1
0.002623
2.2
0.010937
9.1
Adults
50+
yrs.
0.000006
<
1
0.001857
1.6
0.008014
6.7
Females
13­
49
yrs.
0.000014
<
1
0.002526
2.1
0.010907
9.1
Page
66
of
125
The
chronic
results
listed
below
assume
100%
of
the
total
arsenic
concentration
is
either
MMA
(
Table
6.1.2.3c)
or
DMA
(
Table
6.1.2.3d).
The
results
for
the
chronic
dietary
risk
estimates
for
food
exposure
to
MMA
and
DMA,
respectively,
are
not
of
concern
for
the
U.
S.
population
and
all
population
subgroups,
nor
are
the
chronic
risk
estimates
of
concern
for
the
food
and
drinking
water
aggregate
exposure
to
MMA.

Table
6.1.2.3c:
Chronic
Dietary
Risk
Results
from
the
Cotton
Use
for
the
Organic
Arsenical
Herbicides
Using
DEEM
FCID
with
the
MMA
cPAD
of
0.03
mg/
kg/
day
Food
only
Food
+
Cotton
Water
Food
+
Turf
Water
Population
Subgroup
Exposure
(
mg/
kg/
day)
%
cPAD
Exposure
(
mg/
kg/
day)
%
cPAD
Exposure
(
mg/
kg/
day)
%
cPAD
U.
S.
Population
0.000001
<
1
0.000233
<
1
0.002699
9.0
All
Infants
(<
1
yr.)
0.000000
<
1
0.000760
2.5
0.008845
29.5
Children
1­
2
yrs.
0.000002
<
1
0.000346
1.2
0.004008
13.4
Children
3­
5
yrs.
0.000002
<
1
0.000325
1.1
0.003753
12.5
Children
6­
12
yrs.
0.000002
<
1
0.000224
<
1
0.002589
8.6
Youth
13­
19
yrs.
0.000001
<
1
0.000169
<
1
0.001951
6.5
Adults
20­
49
yrs.
0.000001
<
1
0.000217
<
1
0.002520
8.4
Adults
50+
yrs.
0.000000
<
1
0.000228
<
1
0.002651
8.8
Females
13­
49
yrs.
0.000001
<
1
0.000216
<
1
0.002509
8.4
Table
6.1.2.3d:
Chronic
Dietary
Risk
Results
from
the
Cotton
Use
for
the
Organic
Arsenical
Herbicides
Using
DEEM
FCID
with
the
DMA
cPAD
of
0.014
mg/
kg/
day
Food
only
Food
+
Cotton
Water
Food
+
Turf
Water
Population
Subgroup
Exposure
(
mg/
kg/
day)
%
cPAD
Exposure
(
mg/
kg/
day)
%
cPAD
Exposure
(
mg/
kg/
day)
%
cPAD
U.
S.
Population
0.000001
<
1
0.000148
1.1
0.000970
6.9
All
Infants
(<
1
yr.)
0.000000
<
1
0.000484
3.5
0.003179
22.7
Children
1­
2
yrs.
0.000002
<
1
0.000221
1.6
0.001442
10.3
Children
3­
5
yrs.
0.000002
<
1
0.000207
1.5
0.001350
9.6
Children
6­
12
yrs.
0.000002
<
1
0.000143
1.0
0.000931
6.7
Youth
13­
19
yrs.
0.000001
<
1
0.000108
<
1
0.000702
5.0
Adults
20­
49
yrs.
0.000001
<
1
0.000138
1.0
0.000906
6.5
Adults
50+
yrs.
0.000000
<
1
0.000145
1.0
0.000953
6.8
Females
13­
49
yrs.
0.000001
<
1
0.000138
1.0
0.000902
6.4
Page
67
of
125
Results
of
Level
3
Acute
and
Chronic
Dietary
Exposure
Analysis
The
acute
results
listed
below
assume
100%
of
the
total
arsenic
concentration
is
either
MMA
(
Tables
6.1.2.3e)
or
DMA
(
Tables
6.1.2.3f).
The
acute
dietary
risk
estimates
at
the
99.9th
percentile
for
MMA
and
DMA
in
food
are
not
of
concern
for
the
U.
S.
population
and
all
population
subgroups,
nor
are
the
acute
risk
estimates
of
concern
for
the
food
and
drinking
water
aggregate
exposures.

Table
6.1.2.3e:
Acute
Dietary
Risk
Results
at
the
99.9th
%
tile
of
Exposure
from
Cotton
Use
and
All
TDS
Commodities
with
Translations
for
the
Organic
Arsenical
Herbicides
Using
DEEM
FCID
with
the
MMA
aPAD
of
0.1
mg/
kg/
day
Food
only
Food
+
Cotton
Water
Food
+
Turf
Water
Population
Subgroup
Exposure
(
mg/
kg/
day)
%
aPAD
Exposure
(
mg/
kg/
day)
%
aPAD
Exposure
(
mg/
kg/
day)
%
aPAD
U.
S.
Population
0.036201
36.2
0.036779
36.8
0.047609
47.6
All
Infants
(<
1
yr.)
0.028218
29.2
0.031956
31.2
0.089358
89.4
Children
1­
2
yrs.
0.067527
67.5
0.068276
68.3
0.073761
73.8
Children
3­
5
yrs.
0.064264
64.3
0.066282
66.3
0.073885
73.9
Children
6­
12
yrs.
0.043023
43.0
0.044156
44.2
0.049357
49.4
Youth
13­
19
yrs.
0.027242
27.2
0.027821
27.8
0.033211
33.2
Adults
20­
49
yrs.
0.026693
26.7
0.027229
27.2
0.034873
34.9
Adults
50+
yrs.
0.034951
34.9
0.035834
35.8
0.040919
40.9
Females
13­
49
yrs.
0.026445
26.4
0.026685
26.7
0.034338
34.3
Table
6.1.2.3f:
Acute
Dietary
Risk
Results
at
the
99.9th
%
tile
of
Exposure
from
Cotton
Use
and
All
TDS
Commodities
with
Translations
for
the
Organic
Arsenical
Herbicides
Using
DEEM
FCID
with
the
DMA
aPAD
of
0.12
mg/
kg/
day
Food
only
Food
+
Cotton
Water
Food
+
Turf
Water
Population
Subgroup
Exposure
(
mg/
kg/
day)
%
aPAD
Exposure
(
mg/
kg/
day)
%
aPAD
Exposure
(
mg/
kg/
day)
%
aPAD
U.
S.
Population
0.036201
30.2
0.036537
30.4
0.038003
31.7
All
Infants
(<
1
yr.)
0.028218
23.5
0.030201
25.2
0.042138
35.1
Children
1­
2
yrs.
0.067527
56.3
0.067877
56.6
0.069642
58.0
Children
3­
5
yrs.
0.064264
53.6
0.066023
55.0
0.067773
56.5
Children
6­
12
yrs.
0.043023
35.8
0.043792
36.5
0.045716
38.1
Youth
13­
19
yrs.
0.027242
22.7
0.027681
23.1
0.028528
23.8
Adults
20­
49
yrs.
0.026693
22.2
0.027062
22.6
0.028227
23.5
Adults
50+
yrs.
0.034951
29.1
0.035501
29.6
0.036965
20.8
Females
13­
49
yrs.
0.026445
22.0
0.026591
22.2
0.027279
22.7
Page
68
of
125
The
chronic
results
listed
below
assume
100%
of
the
total
arsenic
concentration
is
either
MMA
(
Tables
6.1.2.3g)
or
DMA
(
Tables
6.1.2.3h).
The
chronic
risk
estimates
for
MMA
and
DMA
dietary
exposure
in
food
are
not
of
concern
for
the
U.
S.
population
and
all
population
subgroups
nor
are
the
chronic
risk
estimates
of
concern
for
the
food
and
water
aggregate
exposures.

Table
6.1.2.3g:
Chronic
Dietary
Risk
Results
from
Cotton
Use
and
All
TDS
Commodities
with
Translations
for
the
Organic
Arsenical
Herbicides
Using
DEEM
FCID
with
the
MMA
cPAD
of
0.03
mg/
kg/
day
Food
only
Food
+
Cotton
Water
Food
+
Turf
Water
Population
Subgroup
Exposure
(
mg/
kg/
day)
%
cPAD
Exposure
(
mg/
kg/
day)
%
cPAD
Exposure
(
mg/
kg/
day)
%
cPAD
U.
S.
Population
0.000795
2.6
0.001027
3.4
0.003493
11.6
All
Infants
(<
1
yr.)
0.000611
2.0
0.001371
4.6
0.009456
31.5
Children
1­
2
yrs.
0.001828
6.1
0.002172
7.2
0.005835
19.4
Children
3­
5
yrs.
0.001580
5.3
0.001903
6.3
0.005331
17.8
Children
6­
12
yrs.
0.001000
3.3
0.001223
4.1
0.003587
12.0
Youth
13­
19
yrs.
0.000602
2.0
0.000770
2.6
0.002552
8.5
Adults
20­
49
yrs.
0.000635
2.1
0.000851
2.8
0.003154
10.5
Adults
50+
yrs.
0.000807
2.7
0.001034
3.4
0.003457
11.5
Females
13­
49
yrs.
0.000595
2.0
0.000810
2.7
0.003103
10.3
Table
6.1.2.3h.
Chronic
Dietary
Risk
Results
from
Cotton
Use
and
All
TDS
Commodities
with
Translations
for
the
Organic
Arsenical
Herbicides
Using
DEEM
FCID
with
the
DMA
cPAD
of
0.014
mg/
kg/
day
Food
only
Food
+
Cotton
Water
Food
+
Turf
Water
Population
Subgroup
Exposure
(
mg/
kg/
day)
%
cPAD
Exposure
(
mg/
kg/
day)
%
cPAD
Exposure
(
mg/
kg/
day)
%
cPAD
U.
S.
Population
0.000795
5.7
0.000942
6.7
0.001764
12.6
All
Infants
(<
1
yr.)
0.000611
4.4
0.001094
7.8
0.003790
27.1
Children
1­
2
yrs.
0.001828
13.1
0.002047
14.6
0.003268
23.3
Children
3­
5
yrs.
0.001580
11.3
0.001785
12.8
0.002928
20.9
Children
6­
12
yrs.
0.001000
7.1
0.001142
8.2
0.001930
13.8
Youth
13­
19
yrs.
0.000602
4.3
0.000709
5.1
0.001303
9.3
Adults
20­
49
yrs.
0.000635
4.5
0.000772
5.5
0.001540
11.0
Adults
50+
yrs.
0.000807
5.8
0.000952
6.8
0.001759
12.6
Females
13­
49
yrs.
0.000595
4.2
0.000732
5.2
0.001496
10.7
Page
69
of
125
6.2
Water
Exposure/
Risk
Pathway
Both
the
MMA
and
DMA
water
exposure
assessments
conducted
by
EFED
(
Moore
2006)
were
based
primarily
on
1)
submitted
environmental
fate
studies
on
MSMA
and
DMA,
2)
modeling,
3)
limited
monitoring
for
speciated
forms
of
arsenic,
4)
extensive
monitoring
for
total
arsenic,
and
5)
peer­
reviewed
literature.
Monitoring
sources
included
United
States
Geological
Survey
(
USGS)
(
groundwater
and
surface
water),
BASINS,
STORET
(
surface
water
only),
and
published
literature.
In
most
cases,
monitoring
was
for
total
arsenic
(
unspeciated)
in
areas
not
targeted
for
organic
arsenic
use.
Thus,
most
monitoring
data
are
useful
for
assessing
total
exposure
to
arsenic
(
inorganic
and
organic),
but
are
generally
not
useful
for
estimating
MMA
or
DMA
exposure
resulting
from
pesticide
exposure
as
such.

Based
on
2005
estimates
from
BEAD,
the
major
use
of
cacodylic
acid
is
as
a
cotton
defoliant.
The
major
use
of
DSMA
is
as
an
herbicide
on
cotton
and
the
major
uses
of
MSMA
are
as
an
herbicide
on
cotton
(~
65%
total
use)
and
on
turf
(~
30%).

The
maximum
labeled
rates
for
these
uses
were
modeled
using
PRZM
3.12/
EXAMS
2.98.04
to
determine
estimated
drinking
water
concentrations
(
EDWCs)
in
surface
water.
According
to
the
master
labels
provided
by
the
registrant,
the
maximum
labeled
rate
for
these
uses
are:

Turf:
4
applications
of
MSMA
at
3.35
lbs
ae.
/
A
with
a
10
day
interval
Cotton:
2
applications
of
DSMA
at
1.74
lbs
ae.
/
A
with
a
7
day
interval
AND
1
application
of
DMA
at
1.2
lbs
a.
i.
/
A.

In
aqueous
solution,
the
salts
MSMA
and
DSMA
are
present
in
the
dissociated
form,
as
sodium
ions
and
monomethylarsonic
acid
(
MMA),
a.
k.
a.
MAA.
These
compounds
are
therefore
both
modeled
as
MMA,
using
application
rates
in
lbs
MMA
per
acre.

Both
MMA
and
DMA
can
degrade
to
inorganic
arsenic
(
iAs),
and
DMA
can
be
produced
as
a
degradate
of
MMA,
as
well
as
from
direct
application.
Estimated
concentrations
for
all
three
compounds
are
provided
for
each
use.
EDWCs
for
the
directly
applied
parent
compound,
either
MMA
or
DMA,
were
determined
by
modeling
that
compound
at
the
applied
rate.
Estimates
of
the
amount
of
DMA
present
as
a
degradate
of
MMA
were
determined
by
modeling
as
if
DMA
had
been
applied
directly
at
35%
of
the
MMA
application
rate.
This
value
was
chosen
because
in
all
reviewed
lab
and
field
studies,
no
more
than
35%
of
the
applied
MMA
has
been
present
as
DMA
at
any
time
up
to
one
year.
Inorganic
arsenic
was
calculated
as
a
direct
molar
conversion
from
EDWCs
of
the
applied
compound(
s).
These
estimates
represent
worst­
case
situations
with
maximum
exposures
at
different
times.
Logically,
it
is
not
expected
that
the
maximum
concentration
for
each
compound
will
all
be
present
at
the
same
time
(
i.
e.
concurrently).

The
maximum
area
planted
with
cotton
in
any
watershed
is
20%.
This
percent
cropped
area
(
PCA)
factor
is
used
in
calculations
estimating
exposure
from
use
on
cotton.
Based
on
EFED
policy,
no
PCA
factor
is
used
in
estimating
exposure
from
use
on
turf.
Because
turf
uses
are
not
limited
to
golf
courses,
the
golf
course
adjustment
factor
was
also
not
applied.
Modeling
was
carried
out
with
the
Mississippi
cotton
and
Florida
turf
scenarios,
the
most
vulnerable
scenarios
Page
70
of
125
available
for
these
uses.
Half­
lives,
sorption
coefficients,
and
other
inputs
into
the
modeled
drinking
water
estimates
can
be
found
in
Moore
2006.

6.2.1
Surface
Water
Modeling
for
Drinking
Water
Estimates
Modeling
of
the
application
of
arsenical
pesticides
was
performed
to
predict
acute
and
chronic
concentrations
that
may
reach
drinking
water.
Although
there
are
extensive
monitoring
data
available
for
arsenic,
some
of
it
even
targeted
to
heavy
use
areas,
modeling
remains
a
valuable
tool
to
supplement
the
limitations
of
monitoring.
Most
monitoring
measures
total
arsenic
and
does
not
provide
information
on
speciation.
Monitoring
data
do
not
generally
allow
for
determination
of
the
source
of
contamination.
This
is
particularly
important
for
arsenic,
which
has
multiple
potential
sources,
both
from
natural
background
and
from
various
anthropogenic
activities.
Even
for
those
monitoring
studies
targeted
to
heavy
use
areas,
specific
information
about
application
rates
and
land
use
history
are
not
always
available.
Additionally,
even
targeted
studies
cannot
be
expected
to
capture
short­
lived
peak
concentrations.
In
light
of
these
factors,
and
considering
the
variability
of
arsenic's
environmental
behaviour
with
variable
environmental
conditions,
modeling
is
useful
for
providing
high­
end
estimates
of
speciated
arsenic
concentrations
resulting
from
pesticide
applications
under
the
most
vulnerable
conditions.

To
determine
EDWCs
in
surface
water,
the
Pesticide
Root
Zone
Model
(
PRZM
3.12;
5/
7/
98),
which
simulates
transport
off
the
agricultural
field,
is
run
in
tandem
with
the
Exposure
Analysis
Modeling
System,
(
EXAMS
2.98.04;
6/
13/
97),
which
simulates
the
fate
of
chemicals
in
a
body
of
water.
The
simulated
watershed
is
based
on
an
Index
Reservoir
(
IR)
scenario,
and
a
PCA
adjustment
factor
is
used
to
adjust
for
the
area
within
the
watershed
that
is
planted
to
the
modeled
crop
(
OPP,
2000).
Models
are
run
for
30
years
and
the
reported
EDWCs
represent
the
values
that
are
expected
once
every
ten
years,
based
on
the
30
years
of
daily
values
generated
during
the
simulation.
The
crop
scenarios
used
in
PRZM/
EXAMS
represent
sites
that
are
highly
vulnerable
to
runoff.
In
this
assessment,
the
Mississippi
cotton
and
Florida
turf
scenarios
are
modeled
to
represent
the
major
uses
of
arsenicals
(
see
Moore
2006).

All
species
of
concern
in
this
assessment
(
MMA,
DMA,
and
iAs)
have
distinct
toxicities
(
see
Section
4.0)
therefore,
exposure
to
each
needs
to
be
considered
individually.
Estimated
concentrations
of
each
of
these
compounds
are
therefore
provided
for
each
use.
Compounds
resulting
from
degradation
are
considered
as
well
as
the
directly
applied
herbicides.
Applied
MMA
may
metabolize
to
DMA.
On
cotton,
MMA
and
DMA
can
be
applied
to
the
same
field.
Reported
cotton
MMA
EDWCs,
therefore,
result
from
direct
application
while
cotton
DMA
EDWCs
result
both
from
direct
application
and
from
transformation
of
MMA.
On
turf,
all
EDWCs
are
the
result
of
MMA
application.
Both
MMA
and
DMA
may
also
metabolize
to
inorganic
arsenic.
It
is
impossible
to
determine
the
exact
concentration
of
each
species
that
will
be
present
at
any
one
time
and
each
species
will
reach
its
highest
level
at
different
times.
An
EDWC
for
"
total
arsenic"
has
been
reported
to
indicate
the
maximum
amount
of
arsenic
that
may
be
in
surface
water
as
a
sum
of
all
species
present.
It
is
this
EDWC
that
would
be
compared
to
regulatory
levels,
which
are
set
as
total
arsenic.
Since
it
is
possible
that
all
arsenic
would
be
present
in
the
form
of
inorganic
arsenic,
this
EDWC
also
represents
the
maximum
potential
concentration
of
inorganic
arsenic.
EDWCs
resulting
from
the
maximum
labeled
application
rates
for
cotton
and
turf
are
presented
in
Table
6.2.1.
Page
71
of
125
Table
6.2.1:
EDWCs
(
ppb)
from
maximum
labeled
rates
for
major
uses
of
arsenicals.

Acute
Chronic
Cancer
TURF1
MMA
250.5
127.5
74.6
DMA
102.3
46.5
28.1
Total
As3
135.2
68.8
40.3
COTTON2
MMA
37.4
11.0
5.3
DMA
23.6
7.4
4.3
Total
As3
20.9
7.2
3.9
1
MSMA
applied
4
times
at
3.35
lbs
ae/
A.
2
DSMA
applied
2
times
at
1.74
lbs
ae/
A
&
DMA
applied
1
time
at
1.2
lb
ai/
A.
3
Total
arsenic
is
the
sum,
reported
as
ppb
As,
of
arsenic
that
may
be
present
from
all
applied
and
degradate
species.
It
also
represents
the
maximum
EDWC
of
inorganic
arsenic.

6.2.1.1
Inputs/
Characterization
The
reported
EDWCs
are
based
on
maximum
labeled
application
rates
under
the
most
vulnerable
circumstances.
A
variety
of
management
practices,
environmental
conditions,
and
application
rates
are
possible
and
can
lead
to
different
concentrations.
Exposure
to
arsenicals
may
be
affected
by
less
vulnerable
soils,
typical
application
rates,
application
to
minor
crops,
or
practices
such
as
irrigation
or
spot
treatment.
Sorption
of
arsenical
pesticides
varies
with
soil
characteristics,
which
in
turn
affects
migration
through
soil
to
sources
of
drinking
water.
Sorption
is
expected
to
be
higher
in
soils
with
a
higher
percentage
of
clay
or
with
more
iron
or
aluminum
content
(
Moore
2006).
Additional
estimates
of
surface
water
concentrations
were
modeled
using
higher
Kd
values
to
characterize
possible
exposure
from
application
to
less
vulnerable
soils.
These
results
suggest
that
in
soils
with
median
sorption,
the
acute
EDWCs
would
be
reduced
with
less
change
in
the
chronic
EDWCs.

MMA
degradation
to
DMA
was
simulated
by
modeling
DMA
applied
at
35%
of
the
MMA
rate
with
DMA
input
parameters.
This
simulation
is
based
on
the
assumption
that
a
maximum
of
35%
of
applied
MMA
may
be
present
as
DMA
at
any
one
time
(
see
Moore
2006).
For
cotton,
where
DMA
and
MMA
can
both
be
applied
to
the
same
field
at
different
times
in
the
same
season,
the
time
series
of
concentrations
resulting
from
DMA
applied
directly
was
added
to
that
resulting
from
DMA
as
a
degradate
of
MMA.
The
upper
90%
confidence
limit
was
determined
for
peak
and
average
annual
values
from
this
30
year
time
series.

There
is
uncertainty
associated
with
this
assumption,
which
is
based
on
the
results
of
a
lab
study
on
the
degradation
of
MMA
and
on
calculations
using
the
modeled
half­
lives
of
MMA
and
DMA.
In
both
of
these
approaches,
the
DMA
present
is
being
degraded
as
it
is
formed
and
so,
without
degradation,
would
be
present
in
higher
amounts.
Additional
uncertainty
results
from
modeling
the
DMA
degradate
as
if
it
were
applied
at
the
same
time
as
the
MMA
parent.
Page
72
of
125
Degradation
to
DMA
is
not
a
rapid
transformation
and
so
in
fact,
when
present,
the
degradate
will
appear
at
a
later
date,
dependent
on
the
environmental
conditions.
See
Moore
2006.

Total
arsenic
levels
were
estimated
as
a
direct
molar
conversion
of
the
EDWC
predicted
for
the
applied
organic
arsenical(
s),
and
this
value
also
represents
the
maximum
amount
of
inorganic
arsenic
that
may
reach
surface
water.
The
calculation
of
maximum
inorganic
arsenic
as
a
direct
molar
conversion
of
the
parent
compound's
aquatic
concentration
does
not
necessarily
represent
the
actual
physical
process
 
inorganic
arsenic
is
likely
formed
through
degradation
in
the
soil,
rather
than
after
reaching
surface
water.
This
calculation
still
provides
a
conservative
estimate
of
the
amount
of
inorganic
arsenic
that
may
reach
surface
water.
The
estimate
is
supported
by
a
targeted
monitoring
study
in
cotton
growing
areas
which
found
that
typically,
one
arsenic
species
at
a
time
was
dominant.
Immediately
following
the
period
of
typical
application,
MMA
was
the
dominant
species
and
several
weeks
to
months
later,
the
primary
form
of
arsenic
was
inorganic,
present
at
approximately
the
same
total
arsenic
concentration
as
the
earlier
MMA.

For
cotton,
a
20%
PCA
is
applied
to
the
modeling
results,
according
to
EFED
policy
which
estimates
that
20%
is
the
maximum
area
of
any
watershed
planted
in
cotton
(
OPP,
2000).
It
is
possible
that
arsenicals
are
applied
to
other
crops
within
the
same
watershed,
which
could
lead
to
higher
amounts
of
pesticide
reaching
surface
water.
Use
as
an
herbicide
on
turf
is
the
only
other
application
of
arsenicals
extensive
enough
to
potentially
increase
watershed
scale
concentrations.
Monitoring
data
from
heavy
cotton
use
areas
suggest,
however,
that
the
20%
PCA
still
leads
to
protective
estimates
of
exposure.

No
appropriate
PCA
has
been
determined
for
application
of
pesticides
to
turf.
In
order
to
be
protective,
at
this
time
EFED
policy
is
to
not
apply
any
PCA
for
turf.
The
modeled
EDWCs
for
turf
are
therefore
based
on
the
assumption
that
the
entire
modeled
watershed
has
been
treated
with
pesticide,
which
may
lead
to
overestimation
of
potential
exposure.
Limited
surface
water
monitoring
data
targeted
to
golf
course
use
are
available.
Available
monitoring
data
involves
relatively
small
surface
water
bodies
that
are
completely
surrounded
by
turf
that
may
be
treated
with
arsenicals,
so
they
represent
high
potential
exposure
relative
to
the
index
reservoir.
Nevertheless,
the
data
demonstrate
that
a
significant
amount
of
arsenic
may
reach
surface
water
from
turf
applications
of
arsenicals
and
provide
a
basis
for
evaluating
the
potential
overestimation
of
the
modeled
EDWCs.
The
modeled
chronic
EDWC,
as
total
arsenic,
is
approximately
two
times
the
highest
concentration
found
in
this
limited
monitoring
of
a
high
exposure
situation.

Modeling
relies
on
estimated
fate
parameters
and
assumed
agricultural
practices
to
predict
concentrations
of
pesticides
to
which
humans
may
be
exposed.
There
is
uncertainty
in
all
fate
inputs
used
in
this
assessment,
many
of
which
are
based
on
non­
GLP
studies
with
various
deficiencies.
There
is
also
uncertainty
associated
with
the
method
of
estimating
concentrations
of
the
major
degradates,
DMA
and
inorganic
arsenic.
The
estimate
of
degradation
to
DMA
is
based
on
the
assumption
that
35%
is
the
maximum
amount
of
MAA
that
may
be
present
as
DMA
at
any
one
time.
Because
this
value
is
based
on
data
that
already
includes
some
degradation,
it
may
lead
to
some
underestimation
of
DMA
concentrations.
The
estimation
of
concentrations
of
inorganic
arsenic
is
also
uncertain.
Inorganic
arsenic
EDWCs
are
calculated
as
a
molar
conversion
of
the
EDWCs
of
parent
compounds.
This
is
a
general
estimate
of
the
amount
of
Page
73
of
125
inorganic
arsenic
that
may
reach
surface
water
rather
than
a
direct
calculation
based
on
specific
physical
processes.
Transformation
of
applied
organic
arsenicals
to
inorganic
arsenic
is
a
long
term
process
that
occurs
primarily
through
microbial
activity
in
the
soil,
not
a
rapid
conversion
upon
reaching
water.
Because
of
the
nature
of
these
transformation
processes
and
because
of
inorganic
arsenic's
tendency
to
bind
more
strongly
to
soil
than
the
organic
arsenicals
do,
the
EDWC
of
the
parent
compounds
represents
a
reasonable
upper
bound
on
the
EDWCs
of
inorganic
arsenic.
This
assumption
is
supported
by
empirical
evidence
from
a
targeted
monitoring
study
which
found
that
the
maximum
concentrations
of
inorganic
arsenic
found
in
surface
water
in
areas
of
heavy
application
was
similar
to
the
total
arsenic
resulting
from
parent
compounds
(
Moore
2006).

6.2.2
Drinking
Water
from
Ground
Water
Total
arsenic
in
groundwater
can
reach
very
high
levels
from
natural
sources
alone.
It
is
extremely
variable,
with
national
sampling
results
ranging
from
less
than
the
detection
limit
to
as
high
as
900
ppb.
A
USGS
study
of
around
30,000
locations
found
that
about
10%
of
them
had
groundwater
concentrations
exceeding
10
ppb
total
arsenic,
but
found
no
correlation
between
total
arsenic
levels
and
pesticide
use.
Arsenic
compounds
sorb
strongly
to
soil
and
are
relatively
immobile
in
most
environments,
suggesting
that
significant
leaching
is
unlikely.
This
conclusion
is
supported
by
several
field
studies
which
have
not
detected
arsenic
from
pesticide
application
below
the
top
layers
of
soil.
In
most
situations,
labeled
use
of
arsenical
pesticides
should
not
contribute
significantly
to
the
already
existing
burden
of
arsenic
in
groundwater
from
all
sources,
natural
and
anthropogenic.

Recent
investigations
in
Florida
have
detected
elevated
groundwater
arsenic
levels
below
golf
courses
and
have
demonstrated
that
leaching
from
golf
course
soils
may
be
an
important
process.
In
general,
soils
in
Florida
tend
to
be
very
sandy,
and
golf
courses
are
usually
further
engineered
to
promote
drainage.
In
extreme
environments
like
this,
applied
arsenicals
may
leach
to
groundwater.
Especially
in
areas
like
Florida
where
natural
background
arsenic
levels
are
low,
this
may
lead
to
an
increase
in
groundwater
arsenic.
A
prospective
groundwater
study
is
being
implemented
in
Florida
to
examine
the
potential
for
leaching
in
these
environments.

6.3
Residential
(
Non­
occupational)
Exposure/
Risk
Pathway
It
has
been
determined
there
is
a
potential
for
exposure
in
residential
settings
during
the
application
process
for
homeowners
who
use
products
containing
DMA,
CAMA,
DSMA,
or
MSMA.
There
is
also
a
potential
for
exposure
from
entering
DMA,
CAMA,
DSMA,
or
MSMAtreated
areas,
such
as
lawns
and
golf
courses.
Risk
assessments
have
been
completed
for
both
residential
handler
and
postapplication
scenarios.

In
addition
to
homeowner
uses
in
residential
settings,
DMA,
CAMA,
DSMA,
and
MSMA
are
labeled
for
weed
control
by
commercial
(
occupational)
applicators
in
residential
settings,
which
may
result
in
postapplication
exposures
to
homeowners
and
children
in
residential
settings.
These
potential
postapplication
exposures
have
also
been
considered
in
this
assessment.
Page
74
of
125
6.3.1
Residential
Handler
Exposures
and
Risks
HED
uses
the
term
"
handlers"
to
describe
those
individuals
who
are
involved
in
the
pesticide
application
process.
HED
believes
that
there
are
distinct
tasks
related
to
applications
and
that
exposures
can
vary
depending
on
the
specifics
of
each
task.

6.3.1.1
Inputs
and
Assumptions
for
Residential
Handler
Risks
 
Residential
handler
exposure
scenarios
are
considered
to
be
short­
term
only,
due
to
the
infrequent
use
patterns
associated
with
homeowner
products.

 
A
tiered
approach
for
personal
protection
using
increasing
levels
of
PPE
is
not
used
in
residential
handler
risk
assessments.
Homeowner
handler
assessments
are
based
on
the
assumption
that
individuals
are
wearing
shorts,
short­
sleeved
shirts,
socks,
and
shoes.

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

HED
has
determined
that
there
are
potential
exposure
to
residential
mixer,
loader,
and
applicators
(
handlers)
during
the
usual
use­
patterns
associated
with
cacodylic
acid,
CAMA
and
DSMA/
MSMA.
Based
on
the
supported
use
patterns,
HED
has
determined
that
there
are
a
number
of
potential
exposure
scenarios
associated
with
the
use
of
the
organic
arsenicals
(
see
Smith
2006).

The
duration
of
exposure
for
residential
populations
is
assumed
to
be
short­
term
only,
since
lawn
renovation
occurs
only
once
a
year,
every
five
years
or
more
and
weed
control
occurs
about
once
a
month
during
the
weed
growing
season
of
3
months.
Page
75
of
125
Table
6.3.1.1a:
Residential
Handler
Short­
and
Intermediate­
term
Dermal
and
Inhalation
Exposure
to
DMA
Baseline
Unit
Exposures
Baseline
MOEs
Exposure
Scenario
Crop
or
Target
Application
Rate
(
lb
ai/
acre)
Area
Treated
Daily
(
acres)
Dermal
(
mg/
lb
ai)
Inhalation
(
ug/
lb
ai)
Dermal
Inhalation
Mixer/
Loader/
Applicator
Lawn
edging
7.72
0.5
38
2.7
140
29000
Mixing/
Loading/
Applying
Liquid
Concentrates
with
Low
Pressure
Handwand
(
ORETF)
(
1)
Lawn
renovation
7.3
0.5
38
2.7
150
31000
Lawn
edging
7.72
0.5
11
17
490
4700
Lawn
renovation
7.3
0.5
11
17
520
4900
Mixing/
Loading/
Applying
Liquid
Concentrates
with
Hose­
End
Sprayer
(
Residential
ORETF
data)
(
2)
Non­
crop
7.3
0.5
11
17
520
4900
Lawn
edging
7.72
0.5
2.6
11
2100
7200
Lawn
renovation
7.3
0.5
2.6
11
2200
7600
Loading/
Applying
Liquid
Concentrates
with
RTU
Hose­
End
Sprayer
(
Residential
ORETF
data)
(
3)
Non­
crop
7.3
0.5
2.6
11
2200
7600
Lawn
edging
0.00018
0.023
11
16
11000
110000
Mixing/
Loading/
Applying
Liquid
Concentrates
with
a
Watering
Can
(
using
ORETF
residential
hoseend
data)
(
4)
Lawn
renovation
0.00017
0.023
11
16
11000
110000
Lawn
edging
0.00018
0.023
54
19
2200
91000
Lawn
renovation
0.00017
0.023
54
19
2300
96000
Applying
Ready
to
Use
Formulations
via
Trigger­
Pump
Sprayer
(
ORETF)
(
5)
Non­
crop
0.00017
0.023
54
19
2300
96000
Page
76
of
125
Table
6.3.1.1b:
Residential
Handler
Short­
and
Intermediate­
term
Dermal
and
Inhalation
Exposure
to
CAMA
Baseline
Unit
Exposure
Baseline
MOEs
Exposure
Scenario
Crop
or
Target
App
Rate
(
lb
ai/
A)
App
Rate
of
MMA
(
lb
ai/
A)
Area
Treated
Daily
(
acres)
Dermal
(
mg/
lb
ai)
Inhalation
(
ug/
lb
ai)
Dermal
Inhalation
Mixer/
Loader/
Applicator
Lawn
and
ornamental
turf
(
on
grasses
other
than
Bent)
5
4.4
0.5
38
2.7
840
52000
Lawn
and
ornamental
turf
(
on
Bermuda
and
Zoysia
grass)
4.182
3.7
0.5
38
2.7
1000
62000
Mixing/
Loading/
Apply
ing
Liquid
Concentrates
with
Low
Pressure
Handwand
(
ORETF)
(
1)
Lawn
and
ornamental
turf
(
on
bentgrass)
2.5
2.2
0.5
38
2.7
1700
100000
Lawn
and
ornamental
turf
(
on
grasses
other
than
Bent)
5
4.4
0.5
11
17
2900
8200
Lawn
and
ornamental
turf
(
on
Bermuda
and
Zoysia
grass)
4.182
3.7
0.5
11
17
3500
9800
Mixing/
Loadin
g/
Applying
Liquid
Concentrates
with
Hose­
End
Sprayer
(
Residential
ORETF
data)
(
2)
Lawn
and
ornamental
turf
(
on
bentgrass)
2.5
2.2
0.5
11
17
5800
16000
Lawn
and
ornamental
turf
(
on
grasses
other
than
Bent)
5
4.4
0.023
54
19
13000
160000
Lawn
and
ornamental
turf
(
on
Bermuda
and
Zoysia
grass)
4.182
3.7
0.023
54
19
15000
190000
Applying
Ready
to
Use
Formulations
via
Trigger­
Pump
Sprayer
(
ORETF)
(
3)

Lawn
and
ornamental
turf
(
on
bentgrass)
2.5
2.2
0.023
54
19
26000
320000
Page
77
of
125
Table
6.3.1.1c:
Residential
Handler
Short­
and
Intermediate­
term
Dermal
and
Inhalation
Exposure
to
DSMA
Baseline
Unit
Exposure
Baseline
MOEs
Exposure
Scenario
Crop
or
Target
App
Rate
of
MSMA
or
DSMA
(
lb
ai/
acre)
App
Rate
of
MMA
(
lb
ai/
acre)
Area
Treated
Daily
(
acres)
Dermal
(
mg/
lb
ai)
Inhalation
(
ug/
lb
ai)
Dermal
Inhalation
Mixer/
Loader/
Applicator
Mixing/
Loading/
Applying
Liquid
Concentrates
with
Low
Pressure
Handwand
(
ORETF
­­
ground
directed)
(
1)
lawns
and
ornamental
turf
3.293
2.5
0.5
38
2.7
1500
91000
Mixing/
Loading/
Applying
Liquid
Concentrates
with
Hose­
End
Sprayer
(
Residential
ORETF
data)
(
2)
lawns
and
ornamental
turf
3.293
2.5
0.5
11
17
5100
14000
Loading/
Applying
Liquid
Concentrates
with
RTU
Hose­
End
Sprayer
(
Residential
ORETF
data)
(
3)
lawns
and
ornamental
turf
3.293
2.5
0.5
2.6
11
21000
22000
Loading/
Applying
Granulars
via
Push
Type
Spreader
(
ORETF­
LCO
data)
(
4)
lawns
and
ornamental
turf
3.293
2.5
0.5
0.67
0.88
83000
280000
Loading/
Applying
Granulars
via
Belly
Grinder
(
5)
lawns
and
ornamental
turf
3.293
2.5
0.5
110
62
510
3900
Page
78
of
125
Table
6.3.1.1d:
Residential
Handler
Short­
and
Intermediate­
term
Dermal
and
Inhalation
Exposure
to
MSMA
Baseline
Unit
Exposure
Baseline
MOEs
Exposure
Scenario
Crop
or
Target
App
Rate
of
MSMA
(
lb
ai/
acre)
App
Rate
of
MMA
(
lb
ai/
acre)
Area
Treated
Daily
(
acres)
Dermal
(
mg/
lb
ai)
Inhalation
(
ug/
lb
ai)
Dermal
Inhalation
Mixer/
Loader/
Applicator
lawns
and
ornamental
turf
3.9204
3.4
0.5
38
2.7
1100
67000
lawns
and
ornamental
turf
2.6136
2.3
0.5
38
2.7
1600
100000
Mixing/
Loading/
Applying
Liquid
Concentrates
with
Low
Pressure
Handwand
(
ORETF
­­
ground
directed)
(
1)
lawns
and
ornamental
turf
2.178
1.9
0.5
38
2.7
2000
120000
lawns
and
ornamental
turf
3.9204
3.4
0.5
11
17
3800
11000
lawns
and
ornamental
turf
2.6136
2.3
0.5
11
17
5600
16000
Mixing/
Loading/
Applying
Liquid
Concentrates
with
Hose­
End
Sprayer
(
Residential
ORETF
data)
(
2)
lawns
and
ornamental
turf
2.178
1.9
0.5
11
17
6800
19000
3.9204
3.4
0.5
2.6
11
16000
17000
2.6136
2.3
0.5
2.6
11
24000
25000
Loading/
Applying
Liquid
Concentrates
with
RTU
Hose­
End
Sprayer
(
Residential
ORETF
data)
(
3)
lawns
and
ornamental
turf
2.178
1.9
0.5
2.6
11
29000
30000
6.3.1.2
Summary
of
Residential
Handler
Risks
All
risks
(
i.
e.,
MOEs)
associated
with
the
scenarios
are
not
of
concern;
all
MOEs
were
>
100
for
DMA,
CAMA,
MSMA,
and
DSMA.

In
order
to
refine
this
residential
risk
assessment,
more
data
on
actual
use
patterns
including
rates,
timing,
and
areas
treated
would
better
characterize
cacodylic
acid,
CAMA
and
MSMA/
DSMA
risks.
Exposure
studies
for
many
equipment
types
that
lack
data
or
that
are
not
well
represented
in
PHED
(
e.
g.,
because
of
low
replicate
numbers
or
data
quality)
should
also
be
Page
79
of
125
considered
based
on
the
data
gaps
identified
above
and
based
on
a
review
of
the
quality
of
the
data
used
in
this
assessment.

6.3.2
Residential/
Non­
occupational
Postapplication
Exposures
and
Risks
HED
uses
the
term
"
postapplication"
to
describe
exposures
to
individuals
that
occur
as
a
result
of
being
in
an
environment
that
has
been
previously
treated
with
a
pesticide.
Cacodylic
acid,
CAMA,
and
MSMA/
DSMA
can
be
used
in
many
areas
that
can
be
frequented
by
the
general
population
including
residential
areas
(
e.
g.,
home
lawns
and
gardens).
As
a
result,
individuals
can
be
exposed
by
entering
these
areas,
if
they
have
been
previously
treated.
In
addition,
all
of
these
arsenic
compounds
are
expected
to
accumulate
in
the
soil
and
not
degrade
over
time.

6.3.2.1
Residential
Postapplication
Inputs
and
Assumptions
A
wide
array
of
individuals
of
varying
ages
can
potentially
be
exposed
to
cacodylic
acid,
CAMA
or
MSMA/
DSMA
when
they
are
in
areas
that
have
been
previously
treated.
Postapplication
exposure
scenarios
were
developed
for
each
residential
setting
where
cacodylic
acid,
CAMA
or
MSMA/
DSMA
can
be
used.
The
scenarios
likely
to
result
in
postapplication
exposures
are
as
follows:

 
Dermal
exposure
from
residue
on
lawns
(
adult
and
toddler);
 
Hand­
to­
mouth
transfer
of
residues
on
lawns
(
toddler);
 
Ingestion
of
pesticide
treated
grass
(
toddler);
and
 
Incidental
ingestion
of
soil
from
pesticide­
treated
residential
areas
(
toddler).

HED
relies
on
a
standardized
approach
for
completing
residential
risk
assessments
that
is
based
on
current
labels
and
Agency
guidance.
When
the
guidance
in
current
labels
and
these
documents
is
considered,
it
is
clear
that
HED
should
consider
children
of
differing
ages
as
well
as
adults
in
its
assessments.
It
is
also
clear
that
different
age
groups
should
be
considered
in
different
situations.
The
populations
that
were
considered
in
the
assessment
include:

 
Residential
Adults:
these
individuals
are
members
of
the
general
population
that
are
exposed
to
chemicals
by
engaging
in
activities
at
their
residences
(
e.
g.,
in
their
lawns
or
gardens)
and
also
in
areas
not
limited
to
their
residence
(
e.
g.,
golf
courses
or
parks)
previously
treated
with
a
pesticide.
These
kinds
of
exposures
are
attributable
to
a
variety
of
activities
and
are
usually
addressed
by
HED
in
risk
assessments
by
considering
a
representative
activity
as
the
basis
for
the
exposure
calculation.

 
Residential
Children:
children
are
members
of
the
general
population
that
can
also
be
exposed
in
their
residences
(
e.
g.,
on
lawns
and
other
residential
turf
grass
areas).
These
kinds
of
exposures
are
attributable
to
a
variety
of
activities
such
as
playing
outside.
Toddlers
have
been
selected
as
the
sentinel
(
representative)
population
for
the
turf
assessment.
Youth­
aged
children
(
ages
10
to
12)
are
considered
the
sentinel
population
for
a
golfing
assessment,
because
it
is
likely
that
children
of
this
age
would
be
playing
golf.
Page
80
of
125
6.3.2.2
Residential/
Non­
occupational
Postapplication
Risk
Summary
Adults
The
following
tables
show
the
postapplication
MOE
values
calculated
for
adults
after
lawn
and
home
garden
applications
of
cacodylic
acid,
CAMA
or
DSMA/
MSMA.
For
all
adult
scenarios
for
DMA,
CAMA,
DSMA,
and
MSMA,
short­
term
MOEs
are
>
100
for
all
scenarios.

Table
6.3.2.2a:
Adult
Residential
Risk
Estimates
for
Postapplication
Exposure
to
DMA
Exposure
Scenario
Route
of
Exposure
Application
Type
Application
Rate
(
lb
ai/
acre)
MOE
at
Day
0
Spray
 
Lawn
Edging
7.72
170
Residential
Turf
(
High
Contact
Activities)
Spray
 
Broadcast
7.3
180
Spray
 
Lawn
Edging
7.72
710
Residential
Turf
(
Mowing)
Spray
 
Broadcast
7.3
750
Spray
 
Lawn
Edging
7.72
180
Home
Garden
(
Ornamentals)
Spray
 
Broadcast
7.3
190
Spray
 
Lawn
Edging
7.72
2,400
Golfer
Dermal
Spray
 
Broadcast
7.3
2,600
Table
6.3.2.2b:
Adult
Residential
Risk
Estimates
for
Postapplication
Exposure
to
CAMA
Exposure
Scenario
Route
of
Exposure
Application
Type
MMA
Application
Rate
(
lb
ai/
acre)
MOE
at
Day
0
Residential
Turf
(
High
Contact
Activities)
4.4
980
Residential
Turf
(
Mowing)
4.4
4,200
Home
Garden
(
Ornamentals)
4.4
1,100
Golfer
Dermal
Liquid
4.4
14,000
Page
81
of
125
Table
6.3.2.2c:
Adult
Residential
Risk
Estimates
for
Postapplication
Exposure
to
DSMA
Exposure
Scenario
Route
of
Exposure
Application
Type
MMA
Application
Rate
(
lb
ai/
acre)
MOE
at
Day
0
Residential
Turf
(
High
Contact
Activities)
2.5
1,700
Residential
Turf
(
Mowing)
2.5
7,300
Home
Garden
(
Ornamentals)
2.5
1,900
Golfer
Dermal
Spray
2.5
25,000
Table
6.3.2.2d:
Adult
Residential
Risk
Estimates
for
Postapplication
Exposure
to
MSMA
Exposure
Scenario
Route
of
Exposure
Application
Type
MMA
Application
Rate
(
lb
ai/
acre)
MOE
at
Day
0
Residential
Turf
(
High
Contact
Activities)
3.4
1,300
Residential
Turf
(
Mowing)
3.4
5,400
Home
Garden
(
Ornamentals)
3.4
1,400
Golfer
Dermal
Spray
3.4
18,000
Youths
(
11­
12
years
old)
Risks
(
MOEs)
to
youths
were
calculated
for
postapplication
risks
following
the
application
of
DMA,
CAMA,
DSMA,
and
MSMA
to
home
lawns.
The
tables
below
summarize
the
risk
assessment
for
youths.
Short­
term
MOEs
for
DMA,
CAMA,
DSMA,
and
MSMA
for
these
youths
were
>
100
for
all
scenarios
considered.

Table
6.3.2.2e:
Youths
Residential
Risk
Estimates
for
Postapplication
Exposure
to
DMA
Exposure
Scenario
Route
of
Exposure
Application
Type
Application
Rate
(
lb
ai/
acre)
MOE
at
Day
0
Spray
 
Lawn
Edging
7.72
400
Residential
Turf
(
Mowing)
Spray
 
Broadcast
7.3
420
Spray
 
Lawn
Edging
7.72
410
Home
Garden
(
Ornamentals)
Spray
 
Broadcast
7.3
430
Spray
 
Lawn
Edging
7.72
1,400
Golfer
Dermal
Spray
 
Broadcast
7.3
1,400
Page
82
of
125
Table
6.3.2.2f:
Youths
Residential
Risk
Estimates
for
Postapplication
Exposure
to
CAMA
Exposure
Scenario
Route
of
Exposure
Application
Type
MMA
Application
Rate
(
lb
ai/
acre)
MOE
at
Day
0
Residential
Turf
(
Mowing)
4.4
2,300
Home
Garden
(
Ornamentals)
4.4
2,400
Golfer
Dermal
Spray
4.4
7,900
Table
6.3.2.2g:
Youths
Residential
Risk
Estimates
for
Postapplication
Exposure
to
DSMA
Exposure
Scenario
Route
of
Exposure
Application
Type
MMA
Application
Rate
(
lb
ai/
acre)
MOE
at
Day
0
Residential
Turf
(
Mowing)
2.5
4,100
Home
Garden
(
Ornamentals)
2.5
4,200
Golfer
Dermal
Spray
2.5
14,000
Table
6.3.2.2h:
Youths
Residential
Risk
Estimates
for
Postapplication
Exposure
to
MSMA
Exposure
Scenario
Route
of
Exposure
Application
Type
MMA
Application
Rate
(
lb
ai/
acre)
MOE
at
Day
0
Residential
Turf
(
Mowing)
3.4
3,000
Home
Garden
(
Ornamentals)
3.4
3,100
Golfer
Dermal
Spray
3.4
10,000
Toddler
(
3
year
old)
Risks
(
MOEs)
to
toddlers
were
calculated
for
postapplication
risks
following
the
application
of
DMA,
CAMA,
DSMA,
and
MSMA
to
home
lawns.
The
tables
below
summarize
the
risk
assessment
for
toddlers.
The
target
level
of
concern
for
DMA,
CAMA,
DSMA,
and
MSMA
dermal
scenarios
and
for
CAMA,
DSMA,
and
MSMA
incidental
oral
scenarios
is
100
(
i.
e.,
MOEs
 
100
is
not
of
concern
to
HED).
The
target
level
of
concern
for
DMA
incidental
oral
scenarios
is
30
(
i.
e.,
MOEs
 
30
is
not
of
concern
to
HED),
since
the
endpoint
is
a
BMDL10.
Short­
term
incidental
oral
MOEs
for
DMA
for
toddlers
were
<
30
for
the
hand­
to­
mouth
activity
and
object­
to­
mouth
activities
on
turf.
Short­
term
incidental
oral
MOEs
for
incidental
soil
ingestion
of
DMA
were
greater
than
30
and
not
of
concern.
Short­
term
dermal
MOEs
for
DMA
were
>
100
and
were
also
not
of
concern.
Short­
term
dermal
and
incidental
oral
MOEs
for
CAMA,
DSMA,
and
MSMA
for
toddlers
were
>
100
for
all
scenarios
considered.
Page
83
of
125
Table
6.3.2.2i:
Toddler
Residential
Risk
Estimates
for
Postapplication
Exposure
to
DMA
Exposure
Scenario
Route
of
Exposure
Application
Type
Application
Rate
(
lb
ai/
A)
MOE
­­
Day
0
Spray
 
Lawn
Edging
7.72
100
Residential
Turf
(
High
Contact
Activities)
Dermal
Spray
 
Broadcast
7.3
110
Spray
 
Lawn
Edging
7.72
4
Hand
to
Mouth
Activity
on
Turf
Spray
 
Broadcast
7.3
4
Spray
 
Lawn
Edging
7.72
15
Object
to
Mouth
Activity
on
Turf
Spray
 
Broadcast
7.3
16
Spray
 
Lawn
Edging
7.72
1,100
Incidental
Soil
Ingestion
Oral
Spray
 
Broadcast
7.3
1,200
Table
6.3.2.2j:
Toddler
Residential
Risk
Estimates
for
Postapplication
Exposure
to
CAMA
Exposure
Scenario
Route
of
Exposure
Application
Type
MMA
Application
Rate
(
lb
ai/
A)
MOE
­­
Day
0b
Residential
Turf
(
High
Contact
Activities)
Dermal
4.4
580
Hand
to
Mouth
Activity
on
Turf
4.4
110
Object
to
Mouth
Activity
on
Turf
4.4
430
Incidental
Soil
Ingestion
Oral
Spray
4.4
32,000
Table
6.3.2.2k:
Toddler
Residential
Risk
Estimates
for
Postapplication
Exposure
to
DSMA
Exposure
Scenario
Route
of
Exposure
Application
Type
MMA
Application
Rate
(
lb
ai/
A)
MOE
­­
Day
0b
Residential
Turf
(
High
Contact
Activities)
Dermal
2.5
1,000
Hand
to
Mouth
Activity
on
Turf
2.5
190
Object
to
Mouth
Activity
on
Turf
2.5
750
Incidental
Soil
Ingestion
Oral
Spray
2.5
56,000
Page
84
of
125
Table
6.3.2.2l:
Toddler
Residential
Risk
Estimates
for
Postapplication
Exposure
to
MSMA
Exposure
Scenario
Route
of
Exposure
Application
Type
MMA
Application
Rate
(
lb
ai/
A)
MOE
­­
Day
0b
Residential
Turf
(
High
Contact
Activities)
Dermal
3.4
760
Hand
to
Mouth
Activity
on
Turf
3.4
140
Object
to
Mouth
Activity
on
Turf
3.4
550
Incidental
Soil
Ingestion
Oral
Spray
3.4
41,000
HED
considered
a
number
of
exposure
scenarios
for
products
that
can
be
used
in
the
residential
environment
representing
different
segments
of
the
population
including
toddlers,
youth­
aged
children,
and
adults.
Short­
term
noncancer
MOEs
were
calculated
for
all
scenarios.
Cancer
risks
were
not
calculated,
since
no
toxicological
endpoint
for
cancer
was
selected.
In
residential
settings,
HED
does
not
use
restricted­
entry
intervals
or
other
mitigation
approaches
to
limit
postapplication
exposures,
because
they
are
viewed
as
impractical
and
not
enforceable.
As
such,
risk
estimates
on
the
day
of
application
are
the
key
concern.

In
the
assessment
for
residential
postapplication
exposure
and
risk,
there
are
risks
of
concern
for
DMA,
as
they
are
currently
used
in
a
residential
environment.
The
endpoint
used
to
assess
these
incidental
oral
exposures
(
BMDL10)
comes
from
data
measured
at
10
weeks
of
DMA
exposure
in
the
feed
to
female
rats
(
Arnold
et
al,
1999).
However,
Cohen
et
al,
(
2001)
shows
that
regenerative
proliferation
occurred
as
early
as
1
week
into
the
DMA
exposure.
HED
believes
that
using
the
Arnold
(
1999)
study
(
with
the
Cohen
2001
study
as
characterization)
in
conjunction
with
Day
0
DMA
residues
(
calculated
from
the
labeled
application
rates),
constitutes
the
use
of
the
best
available
data
and
that
the
results
can
be
considered
conservative
for
risk
assessment
purposes.

In
order
to
refine
this
residential
assessment,
data
on
actual
use
patterns
including
rates,
timing,
and
the
kinds
of
tasks
performed
are
required
to
better
characterize
DMA,
CAMA,
DSMA,
and
MSMA
risks.

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

In
general,
exposures
from
various
sources
(
routes)
are
aggregated
only
when
the
toxic
effects,
determined
by
the
endpoint
selected
for
that
route,
are
the
same.
In
this
case,
exposure/
risks
Page
85
of
125
from
the
dermal
and
inhalation
routes
could
not
be
aggregated
with
exposures/
risks
by
the
oral
route
since
the
toxic
effects/
target
organs
are
not
the
same.

HED
combines
residential
risks
resulting
from
exposures
to
individual
applications
when
it
is
likely
they
can
occur
simultaneously
based
on
the
use
pattern
and
the
behavior
associated
with
the
exposed
population.
For
DMA,
CAMA,
DSMA,
and
MSMA,
HED
has
combined
risks
(
i.
e.,
MOEs)
for
different
kinds
of
exposures
for
the
following
scenario:
for
toddlers
on
turf
scenarios
 
hand­
to­
mouth
plus
object­
to­
mouth
plus
soil
ingestion.

The
exposures
of
interest,
as
required
under
FQPA,
are
dietary
(
food
and
water)
and
residential/
recreational
exposures
to
a
common
species
of
arsenic
that
any
one
individual
or
group
of
individuals
might
be
subject.
As
noted
in
section
4.0,
the
toxicities
and
target
organs
of
the
different
species
of
arsenic
(
MMA,
DMA,
iAs)
are
dissimilar
and
the
potential
risks
from
multiple
sources
must
be
viewed
as
one
species
or
the
other
to
give
a
range
of
possibilities.
Since
DMA
is
used
on
cotton,
and
MSMA/
DSMA
are
used
on
cotton
(
cottonseed),
and
all
the
MMA
salts
and
DMA
have
residential/
recreational
uses,
an
individual
could
have
multiple
exposures
to
organic
arsenic
concurrently
from
several
chemicals
(
Cacodylic
acid,
MSMA,
DSMA
and
CAMA),
by
a
variety
of
sources
(
food,
water,
residential),
and
by
all
routes
(
oral,
dermal,
inhalation).

It
is
generally
accepted
that
there
is
potential
for
persons
consuming
a
variety
of
fruits,
vegetables,
and
meat
products
to
have
exposures
to
multiple
pesticides
over
the
course
of
a
day,
a
season,
or
a
year,
many
with
a
common
degradates
or
transformation
product.
Add
to
this
the
exposures
from
residential/
recreational
uses
and
the
potential
health
risks
are
increased.
Known
agricultural
practices
with
organic
arsenics
on
cotton
(
source
of
cotton
seed
commodities),
for
example,
increase
the
likelihood
that
one
might
be
exposed
to
co­
occurring
residues
of
DMA
from
applications
of
DMA
and
of
MMA
salts.
Conversely,
as
discussed
in
Section
3.0,
under
specific
conditions
one
might
be
exposed
to
residues
of
MMA
from
applications
of
DMA
and
MMA
salts.
There
is
potential
for
co­
occurrence
of
DSMA,
MSMA,
and
DMA
from
sequential
treatments
on
cotton
but
co­
occurrence
from
simultaneous
use
appears
to
be
unlikely.
DSMA
and
MSMA
are
used
as
early­
season
directed­
spray
herbicides
on
cotton;
DMA
is
used
to
defoliate
cotton
late
in
the
growing
season
before
harvest
(
Carter
2006).
Additional
dietary
sources
of
DMA
and
MMA
residues
may
come
from
drinking
water.

7.1
Acute
Aggregate
Risk
The
acute
aggregate
risk
estimate
includes
the
contribution
of
risk
from
dietary
(
food
+
drinking
water)
sources
only.
Acute
risk
estimates
based
on
exposures
to
residues
of
MMA
or
DMA
in
food
alone
do
not
exceed
the
Agency's
level
of
concern,
even
when
commodities
from
the
Total
Diet
Study
and
translations
are
included.
The
maximum
estimated
acute
dietary
(
food
alone)
risk
is
68%
of
the
aPAD
at
the
99.9th
percentile
for
children
1­
2
years
of
age,
assuming
all
exposure
is
to
MMA,
and
56%
aPAD
when
one
assumes
that
all
exposure
is
to
DMA.

Though
some
arsenic
water
monitoring
data
are
available
(
measured
as
total
arsenic),
they
are
extremely
limited,
not
nationally
representative,
and
not
at­
the­
tap
data.
Hence,
they
are
unsuitable
to
be
quantitatively
included
in
an
aggregate
risk
assessment.
Therefore,
EDWCs
Page
86
of
125
were
calculated
from
models,
for
risk
assessment
purposes,
based
on
maximum
application
rates.
The
EDWCs
were
combined
directly
with
exposures
from
food
into
the
acute
dietary
exposure
assessment
to
calculate
aggregate
dietary
(
food
+
water)
risk.
The
advantage
of
this
approach
is
that
the
actual
individual
body
weight
and
water
consumption
data
from
the
CSFII
are
used,
rather
than
assumed
weights
and
consumption
for
broad
age
groups.
Surface
water
EDWCs
were
combined
with
estimated
food
exposure
for
aggregate
risk
assessment
purposes
since
the
calculated
surface
water
estimates
exceed
any
potential
ground
water
estimates
and
therefore,
are
more
conservative.

The
acute
aggregate
food
and
water
analysis
provides
a
range
of
risk
possibilities
when
all
residues
are
assumed
to
be
MMA
or
DMA
to
estimate
dietary
exposure
and
risk.
The
drinking
water
estimate
used
in
this
aggregate
(
food
and
water)
analysis
was
calculated
from
turf
uses,
since
that
allows
for
the
most
conservative
exposure
estimate.
Assuming
that
all
exposures
are
either
to
MMA
or
DMA,
the
maximum
aggregate
dietary
risk
estimates
are
for
infants/
children
at
the
99.9th
percentile
of
exposure
and
are
89%
of
the
aPAD
for
MMA
and
58%
aPAD
for
DMA
and
therefore,
not
of
concern.

Table
7.1a:
Results
of
Acute
Aggregate
Dietary
Exposure
Analysis
for
MMA
Using
DEEM
FCID
95TH
%
TILE
99TH
%
TILE
99.9TH
%
TILE
Population
Subgroup
aPAD
(
mg/
kg/
day)
Exposure
%
aPAD
Exposure
%
aPAD
Exposure
%
aPAD
General
U.
S.
Population
0.1
0.012324
12
0.023316
23
0.047609
48
All
Infants
(<
1
year
old)
0.1
0.37384
37
0.055942
56
0.089358
89
Children
1­
2
years
old
0.1
0.019697
20
0.034666
35
0.073761
74
Children
3­
5
years
old
0.1
0.017891
18
0.032945
33
0.073885
74
Children
6­
12
years
old
0.1
0.012480
13
0.022630
23
0.049357
49
Youth
13­
19
years
old
0.1
0.009595
10
0.018331
18
0.033211
33
Females
13­
49
years
old
0.1
0.010871
11
0.018447
18
0.034338
34
Page
87
of
125
Table
7.1b:
Results
of
Acute
Aggregate
Dietary
Exposure
Analysis
for
DMA
Using
DEEM
FCID
95TH
%
TILE
99TH
%
TILE
99.9TH
%
TILE
Population
Subgroup
aPAD
(
mg/
kg/
day)
Exposure
%
aPAD
Exposure
%
aPAD
Exposure
%
aPAD
General
U.
S.
Population
0.12
0.006496
5
0.014781
12
0.038003
32
All
Infants
(<
1
year
old)
0.12
0.015443
13
0.023642
20
0.042138
35
Children
1­
2
years
old
0.12
0.010331
9
0.024297
20
0.069642
58
Children
3­
5
years
old
0.12
0.009143
8
0.026110
22
0.067773
56
Children
6­
12
years
old
0.12
0.006389
5
0.17107
14
0.045716
38
Youth
13­
19
years
old
0.12
0.004633
4
0.012879
11
0.028528
24
Females
13­
49
years
old
0.12
0.005356
4
0.011678
10
0.027279
23
7.2
Short­
term
Aggregate
Risk
Aggregate
short­
term
risk
estimates
include
the
contribution
of
risk
from
chronic
dietary
sources
(
food
+
water)
and
short­
term
residential
or
recreational
sources.
Though
estimated
aggregate
chronic
(
long­
term)
dietary
risks
are
not
of
concern
(
see
Section
7.4),
residential
exposures,
alone,
pose
potential
risks
of
concern
to
children,
specifically
toddlers,
from
postapplication
exposures
to
DMA.
Aggregation
with
dietary
exposures
would
increase
these
concerns
and,
therefore,
for
purposes
of
this
assessment,
dietary
and
residential
exposures
were
not
aggregated.
Information
on
residential
use
patterns
needs
to
be
addressed
for
any
further
refinement
of
the
assessment
to
occur.

HED
combines
risk
values
resulting
from
separate
residential
postapplication
exposure
scenarios
when
it
is
likely
they
can
occur
simultaneously
based
on
the
use­
pattern
and
the
behavior
associated
with
the
exposed
population.
The
tables
below
present
a
summary
of
the
combined
MOE
estimates
for
cacodylic
acid
(
DMA),
CAMA
or
DSMA/
MSMA,
respectively.

The
combined
risk
assessment
for
exposures
to
toddlers
following
home
lawn
applications
was
calculated:

Combined
MOE
=
NOAEL/(
ADDhand­
to­
mouth
+
ADDobject­
to­
mouth
+
ADDincidental
soil
ingestion
+
ADDdermal)

In
the
aggregate
assessment
for
residential
postapplication
exposure
and
risk,
there
are
risks
of
concern
for
DMA
and
CAMA,
as
they
are
currently
used
in
a
residential
environment.
Page
88
of
125
Table
7.2a:
DMA
Residential
Scenarios
for
Combined
Risk
Estimates
­
Toddlers
Margins
of
Exposure
(
MOEs)
(
UF=
30)
Postapplication
Exposure
Scenario
Short­
Term
(
Non­
Dietary)
Total
Non­
Dietary
Risk
Turf
Hand
to
Mouth
4
Object
to
Mouth
15
Turf
(
7.72
lb
ai/
acre)

Incidental
Soil
Ingestion
1,100
3
Hand
to
Mouth
4
Object
to
Mouth
16
Toddler
Turf
(
7.3
lb
ai/
acre)

Incidental
Soil
Ingestion
1,200
3
Table
7.2b:
CAMA
Residential
Scenarios
for
Combined
Risk
Estimates
­
Toddlers
Margins
of
Exposure
(
MOEs)
(
UF=
100)
Postapplication
Exposure
Scenario
Short­
Term
(
Non­
Dietary)
Total
Non­
Dietary
Risk
Turf
Hand
to
Mouth
110
Object
to
Mouth
430
Turf
(
4.4
lb
ai/
acre)

Incidental
Soil
Ingestion
32,000
85
Hand
to
Mouth
130
Object
to
Mouth
510
Turf
(
3.7
lb
ai/
acre)

Incidental
Soil
Ingestion
38,000
101
Hand
to
Mouth
210
Object
to
Mouth
850
Toddler
Turf
(
2.2
lb
ai/
acre)

Incidental
Soil
Ingestion
64,000
170
Page
89
of
125
Table
7.2c:
DSMA
Residential
Scenarios
for
Combined
Risk
Estimates
­
Toddlers
Margins
of
Exposure
(
MOEs)
(
UF=
100)
Postapplication
Exposure
Scenario
Short­
Term
(
Non­
Dietary)
Total
Non­
Dietary
Risk
Turf
Hand
to
Mouth
190
Object
to
Mouth
750
Toddler
Turf
(
2.5
lb
ai/
acre)

Incidental
Soil
Ingestion
56,000
149
Table
7.2d:
MSMA
Residential
Scenarios
for
Combined
Risk
Estimates
­
Toddlers
Margins
of
Exposure
(
MOEs)
(
UF=
100)
Postapplication
Exposure
Scenario
Short­
Term
Oral
(
Non­
Dietary)
Total
Non­
Dietary
Risk
Turf
Hand
to
Mouth
140
Object
to
Mouth
550
Toddler
Turf
(
3.4
lb
ai/
acre)

Incidental
Soil
Ingestion
41,000
110
7.3
Intermediate­
term
Aggregate
Risk
All
residential/
recreational
exposures
are
expected
to
be
short­
term
in
duration.

7.4
Long­
term
Aggregate
Risk
Long­
term
(
noncancer)
aggregate
risk
estimates
include
the
contribution
of
risk
from
chronic
dietary
sources
(
food
+
water)
and
residential
sources.
However,
based
on
the
labeled
uses,
no
long­
term
or
chronic
residential
exposures
are
expected.
Chronic
risk
estimates
from
exposures
to
food
alone,
associated
with
the
use
of
DMA
and
MMA,
do
not
exceed
HED's
level
of
concern
for
any
exposed
population,
based
on
conservative
estimates
of
exposure
that
include
the
Total
Diet
Study
and
translations
to
other
commodities,
as
well
as
EDWCs
resulting
from
turf
uses.
As
in
the
acute
aggregate
assessment,
surface
water
EDWCs
were
calculated
by
EFED
to
estimate
the
potential
contribution
to
the
chronic
exposure
from
drinking
water,
and
the
EDWCs
were
combined
with
chronic
food
exposures
to
estimate
potential
long­
term
aggregate
risks
from
the
uses
of
DMA
and
MMA.
The
drinking
water
estimate
used
in
this
analysis
was
the
1
in
10
year
average.
Page
90
of
125
Table
7.4a:
Results
of
the
Aggregate
Chronic
Dietary
Exposure
Analysis
for
MMA
Using
DEEM
FCID
Population
Subgroup
cPAD
(
mg/
kg/
day)
Exposure
(
mg/
kg/
day)
%
cPAD
General
U.
S.
Population
0.03
0.003493
12
All
Infants
(<
1
year
old)
0.03
0.009456
32
Children
1­
2
years
old
0.03
0.005835
19
Children
3­
5
years
old
0.03
0.005331
18
Children
6­
12
years
old
0.03
0.003587
12
Youth
13­
19
years
old
0.03
0.002552
9
Females
13­
49
years
old
0.03
0.003103
10
Table
7.4b:
Results
of
the
Aggregate
Chronic
Dietary
Exposure
Analysis
for
DMA
Using
DEEM
FCID
Population
Subgroup
cPAD
(
mg/
kg/
day)
Exposure
(
mg/
kg/
day)
%
cPAD
General
U.
S.
Population
0.014
0.001764
13
All
Infants
(<
1
year
old)
0.014
0.003790
27
Children
1­
2
years
old
0.014
0.003268
23
Children
3­
5
years
old
0.014
0.002928
21
Children
6­
12
years
old
0.014
0.001930
14
Youth
13­
19
years
old
0.014
0.001303
9
Females
13­
49
years
old
0.014
0.001496
11
7.5
Aggregate
Cancer
Risk
MMA
was
classified
as
"
no
evidence
for
carcinogenicity,"
based
on
the
lack
of
evidence
of
carcinogenicity
in
rats
and
mice
and
DMA
was
classified
as
"
not
carcinogenic
up
to
doses
resulting
in
regenerative
proliferation;"
therefore,
a
cancer
dietary
analysis
was
not
performed.

7.6
Aggregate
Risk
Summary
OPP
is
confident
that
the
dietary
(
food
+
water)
risk
estimates
do
not
underestimate
the
potential
dietary
exposures.
Since
there
are
no
reliable
methods
to
predict
what
species
of
arsenic
may
be
present
at
any
point
in
time,
and
the
toxicities
and
target
organs
of
the
different
species
are
dissimilar,
estimated
risks
may,
at
the
same
time,
both
under
estimate
and
over
estimate
the
potential
risks
from
any
one
species
of
arsenic.
Page
91
of
125
Residential
exposures,
alone,
pose
potential
risks
of
concern
to
toddlers
from
residential
postapplication
exposures
to
DMA
and
CAMA.
Aggregation
with
dietary
exposures
would
increase
these
concerns.

7.7
"
Total
Arsenic"
and
Exposure
to
Inorganic
Arsenic
The
Federal
Government
and
most
states
have
established
limits
and/
or
screening
levels
for
"
total
arsenic"
(
unspeciated)
exposure
from
a
variety
of
sources;
drinking
water,
air,
and
soil.
Typically
in
monitoring
programs,
arsenic
is
measured
and
reported
as
total
arsenic,
regardless
of
what
species
(
DMA,
MMA,
iAs),
or
mixture
of
species,
may
be
present,
or
what
the
source
is
of
the
arsenic.
These
limits
or
screening
levels
are
established
based
on
risks
(
cancer)
from
exposure
to
iAs.
As
mentioned
previously,
the
differing
species
(
DMA,
MMA,
iAs)
of
arsenic
have
dissimilar
toxicities
and
target
organs;
iAs
being
the
most
toxic.
An
extensive
review
of
the
literature,
have
shown
that
exposure
to
iAs
can
occur
from
the
registered
uses
of
the
organic
arsenicals
and
background
residues,
given
time
and
under
environmental
conditions
that
favor
the
transformation
to
iAs.
In
some
media
(
food,
water,
soil)
and
in
some
parts
of
the
United
States,
the
likelihood
of
exposure
to
iAs
is
higher
than
in
others.
Under
FQPA,
the
Agency
is
required
to
consider
all
potential
sources
of
exposure
to
the
organic
arsenicals,
and
their
metabolites
and/
or
transformation
products.
Since
the
limits
and/
or
screening
levels
are
established
for
total
arsenic
(
all
species
included)
and
there
is
potential
for
transformation
and
exposure
to
iAs
from
the
registered
uses
of
the
organic
arsenicals,
an
analysis
for
potential
risks
from
exposure
to
iAs
was
performed,
which
included
a
comparison
of
estimated
exposures
from
registered
uses
to
existing
regulatory
limits
or
screening
levels.

7.7.1
Dietary
Since
the
dominant
species
of
arsenic
found
in
soil
is
iAs,
conversion
from
applied
MMA
and
DMA
to
iAs
is
expected,
and
it
is
unclear
if
plants
would
methylate
iAs
or
just
pick
it
up
from
the
soil,
HED
must
also
consider
the
possible
dietary
exposure
to
iAs
resulting
from
the
herbicidal
uses.
HED
has
not
performed
a
conventional
dietary
assessment
to
iAs,
but
has
determined
what
percentage
of
the
estimated
dietary
exposure
would
need
to
be
to
iAs
to
reach
our
level
of
concern.

For
exposure
to
the
registered
food
commodity
only,
cottonseed
(
field
trial
data
resulting
from
the
max
application
of
DSMA/
MSMA
and
cacodylic
acid
to
cotton
grown
in
non­
arsenic
containing
soil),
>
100%
of
the
exposure
would
need
to
be
from
iAs
before
HED's
level
of
concern
was
reached
(
1x10­
6);
however,
for
exposure
to
cottonseed
and
cotton
water,
a
maximum
of
~
0.20%
of
the
exposure
could
be
from
iAs
before
HED's
level
of
concern
was
reached,
and
for
exposure
to
cottonseed
and
turf
water,
a
maximum
of
~
0.03%
of
the
exposure
could
be
from
iAs
before
the
level
of
concern
was
reached.
For
exposure
to
the
registered
uses
and
meat,
~
0.26%
of
the
exposure
would
need
to
be
from
iAs
before
HED's
level
of
concern
was
reached.
Though
it
is
unlikely
that
all
of
the
exposure
is
to
organic
arsenic
or
iAs,
this
analysis
demonstrates
that
only
a
small
amount
of
the
total
exposure
needs
to
be
from
iAs
to
reach
HED's
level
of
concern.
Page
92
of
125
Table
7.7.1:
Cancer
Dietary
Exposure
Estimates
from
the
Cotton
Use
for
the
Organic
Arsenical
Pesticides
Using
DEEM
FCID
with
the
iAs
Q*
of
3.67
Cotton
only
Cotton
+
Cotton
Water
Cotton
+
Turf
Water
Cotton
and
Meat
only
Population
Subgroup
%
Exposure
from
iAs
Cancer
Risk
%
Exposure
from
iAs
Cancer
Risk
%
Exposure
from
iAs
Cancer
Risk
%
Exposure
from
iAs
Cancer
Risk
>
100%
1.0E­
04
~
11%
for
MMA1
~
18%
for
DMA2
1.0E­
04
~
1%
for
MMA1
~
2%
for
DMA2
1.0E­
04
~
24%
1.0E­
04
U.
S.
Population
>
100%
1.0E­
06
~
0.11%
for
MMA1
~
0.18%
for
DMA2
1.0E­
06
~
0.01%
for
MMA1
~
0.02%
for
DMA2
1.0E­
06
~
0.24%
1.0E­
06
1.
The
percent
of
exposure
for
MMA
is
calculated
as
follows:
MMA
exp/
iAs
exp
needed
to
reach
target
x
100.
2.
The
percent
of
exposure
for
DMA
is
calculated
as
follows:
DMA
exp/
iAs
exp
needed
to
reach
target
x
100.

7.7.2
Drinking
Water
All
species
of
concern
in
this
assessment
(
MMA,
DMA,
and
iAs)
have
distinct
toxicities
(
see
Section
4.0)
therefore,
EFED
estimated
exposure
to
each
individually
(
see
Table
6.2.1).
Compounds
resulting
from
degradation
are
considered
as
well
as
the
directly
applied
herbicides.
It
is
impossible
to
determine
the
exact
concentration
of
each
species
that
will
be
present
at
any
one
time.
Each
species
will
reach
its
highest
level
at
different
times,
and
it
is
concentrations
from
these
worst­
case
situations
which
EFED
reported.
It
is
not
expected
that
the
maximum
concentrations
for
each
compound
would
all
be
present
at
the
same
time.
EDWCs
were
also
reported
as
total
arsenic,
therefore,
to
indicate
the
maximum
amount
of
arsenic
that
may
be
in
surface
water
as
a
sum
of
all
species
present.
Total
arsenic
levels
were
estimated
as
a
direct
molar
conversion
of
the
EDWC
predicted
for
the
applied
organic
arsenical(
s),
and
this
value
also
represents
the
maximum
amount
of
iAs
that
may
reach
surface
water.
This
calculation
of
maximum
iAs
as
a
direct
molar
conversion
of
the
parent
compound's
aquatic
concentration
does
not
necessarily
represent
the
actual
physical
process
 
iAs
is
likely
formed
through
degradation
in
the
soil,
rather
than
after
reaching
surface
water.
The
concentrations
listed
in
Table
6.2.1
provide
a
conservative
estimate
of
the
amount
of
iAs
that
may
reach
surface
water.

The
Agency's
Office
of
Water
has
established
a
Maximum
Concentration
Level
(
MCL)
for
total
arsenic
of
10
ppb
(
66
FR
6976
January
22,
2001)
based
on
iAs
toxicity
and
current
technologies
(
http://
www.
epa.
gov/
safewater/
arsenic/
mcl.
html).
As
is
shown
in
Table
6.2.1,
estimates
of
exposure
to
iAs
alone
may
possibly
exceed
the
MCL.
Since
the
MCL
was
established
for
total
arsenic,
exposures
to
any
of
the
arsenic
species
in
water
are
potentially
subject
to
regulation.

7.7.3
Residential
Postapplication
Exposure
The
active
ingredients
DMA,
CAMA,
DSMA,
and
MSMA
are
all
organic
species
of
arsenic.
Since
arsenic
is
an
element,
it
is
not
subject
to
biological
or
chemical
degradation
in
the
environment.
CAMA,
DSMA,
and
MSMA
are
salts
of
MMA
and
quickly
covert
to
MMA
when
mixed
in
water
before
application.
Following
application,
under
certain
conditions,
MMA
converts
to
DMA
and/
or
to
iAs.
Similarly,
following
application,
under
certain
conditions,
DMA
converts
to
iAs.
Data
available
to
date
indicate
that
MMA
and
DMA
are
stable
in
the
environment
when
they
remain
on
the
outside
of
the
treated
foliage
of
plants.
They
transform
to
other
species
in
the
environment
only
when
inside
a
plant
or
in
the
soil,
suggesting
microbial
or
Page
93
of
125
enzymatic
involvement.
Therefore,
for
the
purposes
of
HED's
assessment
of
occupational
and
residential
postapplication
exposures
and
risks,
the
dermal
and
incidental
oral
exposures
to
foliar
surfaces
are
conducted
using
the
form
that
was
applied
(
i.
e.,
MMA
when
CAMA,
DSMA,
or
MSMA
was
applied
or
DMA
when
DMA
was
applied).
Postapplication
inhalation
exposures
are
not
a
concern
due
to
the
low
vapor
pressure
of
the
organic
and
inorganic
forms
and
the
infinite
dilution
in
outdoor
environments.

HED
must
consider
the
possible
in­
soil
conversion
of
MMA
to
DMA
or
to
iAs
and
the
possible
conversion
of
DMA
to
iAs
to
accurately
assess
risks
from
postapplication
dermal
exposures
to
the
soil
(
i.
e.,
in
harvesting/
transplanting
sod
or
lawn
renovation)
and
from
postapplication
incidental
oral
exposures
to
toddlers
ingesting
soil.
Several
factors
appear
to
influence
the
conversion
of
organic
arsenic
to
the
inorganic
form
in
soil,
including
soil
organic
matter,
soil
moisture,
soil
temperature
and
the
concentration
and
species
of
the
arsenic
in
the
soil.

HED
generally
assumes
a
degradation
curve
where
the
pesticide
residues
degrade
over
time
to
nontoxic
byproducts
when
assessing
postapplication
exposure
and
risk.
However,
with
the
organic
arsenical
herbicides,
the
degradates,
when
formed,
may
be
more
toxic
than
the
initial
residue
(
i.
e.,
iAs
is
more
toxic
than
DMA
and
DMA
is
more
toxic
dermally
and
orally
than
MMA).
Also,
pesticide
residues
typically
degrade
over
time
to
nondetectable
levels.
However,
arsenic
in
its
inorganic
form
does
not
degrade
and
evidence
indicates
that
it
may
build
up
in
soil
over
time
as
applications
are
repeated.

For
postapplication
dermal
exposures
and
incidental
ingestion
of
soil,
HED
is
concerned
both
about
the
build
up
of
arsenicals
in
the
soil
(
of
any
species)
and
the
possible
degradation
in
soil
to
more
toxic
forms.
At
this
time,
HED
has
no
data
to
estimate
either
the
percent
of
conversion
from
one
form
of
arsenic
to
another
(
i.
e.,
from
a
less
toxic
to
more
toxic
form)
or
the
amount
of
time
necessary
for
the
conversion
to
take
place.
Consequently,
it
is
not
possible
at
this
time
to
perform
a
quantitative
risk
assessment
from
soil
treated
repeatedly
with
organic
arsenical
herbicides.
HED
notes
that
incidental
ingestion
of
soil
by
toddlers
results
in
risks
not
of
concern
when
assessed
for
exposures
following
a
single
application
of
either
MMA
or
DMA.
Even
assuming
that
all
residues
from
four
applications
per
year
(
maximum
allowed)
converted
to
iAs
in
the
soil
were
100%
bioavailable
from
the
soil
 
both
very
conservative
assumptions
 
the
risks
would
not
be
a
concern
when
compared
to
dermal
and
incidental
oral
endpoints
established
for
iAs
by
EPA/
OPP's
Antimicrobial
Division
(
Chen
2001).
However,
the
potential
risks
to
toddlers
incidentally
ingesting
soil
from
an
area
that
had
been
treated
with
compounds
that
transformed
to
iAs
for
several
years
might
be
a
concern,
depending
on
the
amount
of
arsenic
that
remained
onsite
(
versus
runoff
or
leaching)
and
the
degree
of
conversion
to
the
more
toxic
iAs
that
had
occurred.
Likewise,
the
risks
to
adults
dermally
exposed
while
performing
tasks
involving
high
contact
with
the
soil,
such
as
turf
transplanting
or
harvesting,
would
not
be
a
concern
assuming
established
soil
adherence
factors
for
dermal
exposures,
and
that
all
residues
from
four
applications
per
year
(
maximum
allowed)
converted
to
iAs
in
the
soil
and
were
100
percent
bioavailable
from
the
soil.
However,
the
risks
to
adults
contacting
soil
from
an
area
that
had
been
treated
with
compounds
that
transformed
to
iAs
for
several
years
might
be
a
concern,
depending
on
the
amount
of
arsenic
that
remained
on­
site
(
versus
runoff
or
leaching)
and
the
degree
of
conversion
to
the
more
toxic
iAs
that
has
occurred.
Page
94
of
125
HED
has
also
attempted
to
estimate
arsenic
levels
in
soil
and
then
compare
these
values
to
the
Office
of
Solid
Waste
and
Emergency
Response's
(
OSWER)
arsenic
soil
screening
levels
(
SSLs).
SSLs
are
not
national
clean­
up
standards
and
SSLs
alone
do
not
define
"
unacceptable"
levels
of
contaminants
in
soil.
Screening
refers
to
the
process
of
identifying
and
defining
areas,
contaminants,
and
conditions,
at
a
particular
site
that
do
not
require
further
Federal
attention.
Generally,
at
sites
where
contaminant
concentrations
fall
below
SSLs,
no
further
action
or
study
is
warranted
under
the
Comprehensive
Environmental
Response,
Compensation,
and
Liability
Act
(
CERCLA),
commonly
known
as
"
Superfund."
When
contaminant
concentrations
equal
or
exceed
SSLs,
further
study
or
investigation,
but
not
necessarily
clean­
up,
is
warranted.
Detailed
information
on
SSLs
is
available
at:
http://
www.
epa.
gov/
superfund/
resources/
soil.

The
SSL
for
total
arsenic
(
unspeciated)
is
0.4
ppm.
State
cleanup
levels
for
total
arsenic
vary
by
state
and
site
from
0.1
ppm
to
200
ppm
depending
on
land
use
(
i.
e.,
residential,
industrial,
agricultural,
recreational),
background
level,
and
other
factors.
The
arsenic
SSL
is
based
on
a
value
that
corresponds
to
a
10­
6
excess
risk
level
using
the
iAs
cancer
slope
factor.
This
"
target"
hazard
quotient
is
used
to
calculate
the
0.4
ppm
total
arsenic
soil
screening
level,
below
which,
it
is
unlikely
that
sensitive
populations
will
experience
adverse
health
effects
resulting
from
exposure
to
total
arsenic.

In
order
to
estimate
arsenic
levels
in
soil,
HED
assumed
that
all
residues
from
an
application
of
either
MMA
or
DMA
converted
to
iAs
and
were
100%
bioavailable
from
the
soil
(
both
very
conservative
assumptions).
In
all
cases,
after
one
application,
the
arsenic
levels
in
soil
exceeded
the
0.4
ppm
SSL
for
total
arsenic.
HED
believes
the
possibility
of
exceeding
the
arsenic
SSL
would
increase
with
the
number
of
arsenic
applications
as
arsenic
in
its
inorganic
form
does
not
degrade
and
evidence
indicates
that
it
may
build
up
in
soil
overtime
as
applications
are
repeated.
More
detailed
information
regarding
arsenic
degradation,
mobility,
and
soil
buildup
can
be
found
in
Moore
2006.

8.0
Cumulative
Risk
Characterization/
Assessment
The
Food
Quality
Protection
Act
(
1996)
stipulates
that
when
determining
the
safety
of
a
pesticide
chemical,
EPA
shall
base
its
assessment
of
the
risk
posed
by
the
chemical
on,
among
other
things,
available
information
concerning
the
cumulative
effects
to
human
health
that
may
result
from
dietary,
residential,
or
other
non­
occupational
exposure
to
other
substances
that
have
a
common
mechanism
of
toxicity.
The
reason
for
consideration
of
other
substances
is
due
to
the
possibility
that
low­
level
exposures
to
multiple
chemical
substances
that
cause
a
common
toxic
effect
by
a
common
mechanism
could
lead
to
the
same
adverse
health
effect
as
would
a
higher
level
of
exposure
to
any
of
the
other
substances
individually.
A
person
exposed
to
a
pesticide
at
a
level
that
is
considered
safe
may
in
fact
experience
harm
if
that
person
is
also
exposed
to
other
substances
that
cause
a
common
toxic
effect
by
a
mechanism
common
with
that
of
the
subject
pesticide,
even
if
the
individual
exposure
levels
to
the
other
substances
are
also
considered
safe.

Guidance
for
conducting
cumulative
risk
assessments
on
substances
that
have
a
common
mechanism
of
toxicity
is
available
from
the
OPP
website
(
http://
www.
epa.
gov/
pesticides).
In
the
guidance,
it
is
stated
that
a
cumulative
risk
assessment
of
substances
that
cause
a
common
toxic
effect
by
a
common
mechanism
will
not
be
conducted
until
an
aggregate
exposure
assessment
of
Page
95
of
125
each
substance
has
been
completed.
Before
undertaking
a
cumulative
risk
assessment,
HED
will
follow
procedures
for
identifying
chemicals
that
have
a
common
mechanism
of
toxicity
as
set
forth
in
the
"
Guidance
for
Identifying
Pesticide
Chemicals
and
Other
Substances
that
Have
a
Common
Mechanism
of
Toxicity"
(
64
FR
5795­
5796,
February
5,
1999).

HED
did
not
perform
a
cumulative
risk
assessment
as
part
of
this
risk
assessment
for
organic
arsenics
because
HED
has
not
yet
initiated
a
review
to
determine
if
MMA,
or
DMA,
have
a
common
mechanism
of
toxicity
in
humans
with
any
other
chemical
substances.

In
vivo
and
in
vitro
toxicity
studies
indicate
that
the
various
arsenical
compounds
(
MMA,
DMA,
and
iAs)
have
distinct
toxicological
profiles.
Though
the
arsenical
compounds
may
transform
to
each
other
under
certain
conditions,
they
have
distinct
PK
and
PD
differences
that
are
observed
following
direct
oral
exposure.
Therefore,
they
neither
have
a
common
mechanism
of
toxicity
with
each
other,
nor
is
it
currently
apparent
that
any
of
them
have
a
common
mechanism
of
toxicity
with
other
chemical
substances.

9.0
Occupational
Exposure/
Risk
Pathway
DMA
(
cacodylic
acid
or
dimethylarsenic
acid)
is
a
cotton
defoliant
and
is
also
an
herbicide
used
in
agricultural,
commercial,
and
residential
settings
for
the
postemergent
control
of
annual
grasses
and
broadleaf
weeds.
It
is
registered
as
a
liquid
concentrate,
a
pressurized
liquid,
and
a
ready­
to­
use
solution;
and
is
applied
using:
aircraft,
groundboom
sprayer,
rights­
of­
way
sprayer,
handgun
sprayer,
low
pressure
handwand
sprayer,
and
sprinkling
can.

CAMA
is
an
organic
arsenical
herbicide
registered
for
postemergent
weed
control
on
lawns
and
turf
grass.
CAMA
is
formulated
as
a
liquid
concentrate
and
a
ready­
to­
use
solution.
CAMA
is
applied
by
commercial
applicators
using
a
low­
pressure
handwand
sprayer
or
handgun
sprayer.
It
is
applied
by
homeowner
applicators
using
a
low
pressure
handwand
sprayer,
hose­
end
sprayer,
and
ready­
to­
use
"
trigger
pump"
sprayer.

MSMA
and
DSMA
are
organic
arsenical
herbicides
registered
for
weed
control
on
cotton,
under
trees,
vines
and
shrubs,
and
for
lawn
care.
MSMA
technical
is
formulated
as
a
liquid
concentrate,
a
ready­
to­
use
liquid,
and
a
dry
flowable.
DSMA
is
formulated
as
a
liquid
concentrate,
and
a
wettable
powder.
MSMA
and
DSMA
are
applied
by
aircraft,
groundboom,
rights­
of­
way
sprayer,
turf
handgun
sprayer,
low
pressure
handwand
sprayer,
and
sprinkler
can.

At
this
time,
products
containing
DMA,
CAMA
or
MSMA/
DSMA
are
intended
for
both
occupational
and
homeowner
uses.
DMA
is
an
organic
arsenical
cotton
defoliant
and
herbicide
registered
for
weed
control
under
non­
bearing
citrus
trees,
around
buildings,
and
sidewalks
and
for
lawn
renovation.
CAMA
is
an
organic
arsenical
herbicide
registered
for
postemergent
weed
control
on
lawns.
Both
MSMA
and
DSMA
are
organic
arsenical
herbicides
registered
for
weed
control
on
cotton,
for
turf
grass
and
lawns,
and
under
trees,
vines,
and
shrubs.

The
MAA
(
Methanearsonic
Acid)
Task
Force
consists
of
the
primary
registrants
for
DMA,
CAMA,
DSMA,
and
MSMA,
which
are
Luxembourg­
Pamol,
Inc.,
Zeneca
Agricultural
Products/
GP
Biosciences,
Drexel/
APC
Holdings,
and
Albaugh
Inc.
This
Task
Force
provided
a
Page
96
of
125
Master
Label
review
that
contains
maximum
application
rates
and
use
parameters
for
each
active
ingredient.
This
assessment
examines
exposures
using
the
maximum
application
rates
obtained
from
the
Master
Label
(
ML).

DMA
is
formulated
as
a
liquid
concentrate
(
0.6
to
4.9
percent
active
ingredient),
a
pressurized
liquid
(
0.21
percent
active
ingredient),
and
a
ready­
to­
use
solution
(
0.09
to
0.39
percent
active
ingredient).
CAMA
is
formulated
as
a
liquid
concentrate
(
8.4­
10.3%
active
ingredient)
and
a
ready­
to­
use
solution
(
0.5
percent
active
ingredient).
DSMA
is
formulated
as
a
liquid
concentrate
(
12.5­
36.9%),
and
a
wettable
powder
(
63­
81%).
MSMA
technical
is
formulated
as
a
liquid
concentrate
(
7.2­
58.2%),
a
ready­
to­
use
liquid
(
0.4­
2.5%)
and
a
dry
flowable
(
2.3­
55%).

9.1
Short/
Intermediate­
term
Occupational
Handler
Exposure
and
Risk
HED
uses
the
term
"
handlers"
to
describe
those
individuals
who
are
involved
in
the
pesticide
application
process.
HED
believes
that
there
are
distinct
job
functions
or
tasks
related
to
applications
and
that
exposures
can
vary
depending
on
the
specifics
of
each
task.
Job
requirements
(
e.
g.,
amount
of
chemical
to
be
used
in
an
application),
the
kinds
of
equipment
used,
the
target
being
treated,
and
the
level
of
protection
used
by
a
handler
can
cause
exposure
levels
to
differ
in
a
manner
specific
to
each
application
event.

9.1.1
Inputs/
Assumptions
into
Handler
Exposure/
Risk
Estimates
HED
uses
exposure
scenarios
to
describe
the
various
types
of
handler
exposures
that
may
occur
for
a
specific
active
ingredient.
The
use
of
scenarios
as
a
basis
for
exposure
assessment
is
very
common
as
described
in
the
U.
S.
EPA
Guidelines
for
Exposure
Assessment
(
U.
S.
EPA;
Federal
Register
Volume
57,
Number
104;
May
29,
1992).
Information
from
the
current
labels,
use
and
usage
information,
toxicology
data,
and
exposure
data
were
all
key
components
in
the
development
of
the
exposure
scenarios.
HED
has
developed
a
series
of
general
descriptions
for
tasks
that
are
associated
with
pesticide
applications.
Tasks
associated
with
occupational
pesticide
handlers
are
categorized
using
one
of
the
following
terms:

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

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

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

 
Flaggers:
these
individuals
provide
ground
support
to
aerial
applicators
by
indicating
where
the
swath
ends
and
the
next
one
should
begin.
Page
97
of
125
A
chemical
can
produce
different
effects
based
on
how
long
a
person
is
exposed,
how
frequently
exposures
occur,
and
the
level
of
exposure.
HED
classifies
exposures
up
to
30
days
as
shortterm
and
exposures
greater
than
30
days
up
to
several
months
as
intermediate­
term.
HED
completes
both
short­
and
intermediate­
term
assessments
for
occupational
scenarios
in
essentially
all
cases,
because
these
kinds
of
exposures
are
likely
and
acceptable
use/
usage
data
are
not
available
to
justify
deleting
intermediate­
term
scenarios.
Based
on
use
data
and
label
instructions,
HED
believes
that
occupational
MMA
and
DMA
exposures
may
occur
over
a
single
day
or
up
to
weeks
at
a
time
for
many
use­
patterns
and
that
intermittent
exposures
over
several
weeks
also
may
occur.
Some
applicators
may
apply
MMA
(
CAMA,
MSMA,
and/
or
DSMA)
or
DMA
over
a
period
of
weeks,
because
they
are
custom
or
commercial
applicators
who
are
completing
a
number
of
applications
for
a
number
of
different
clients.
Long­
term
handler
exposures
are
not
expected
to
occur
for
MMA
and
DMA.

Other
parameters
are
also
defined
from
use
and
usage
data
such
as
application
rates
and
application
frequency.
HED
always
completes
non­
cancer
risk
assessments
using
maximum
application
rates
for
each
in
order
to
ensure
there
are
no
concerns
for
each
specific
use.
Occupational
handler
exposure
estimates
were
based
on
surrogate
data
from:
(
1)
the
Pesticide
Handlers
Exposure
Database
(
PHED)
and
(
2)
the
Outdoor
Residential
Exposure
Task
Force
(
ORETF).
Generic
protection
factors
(
PFs)
were
used
to
calculate
exposures
when
data
were
not
available.
For
example,
an
80
percent
protection
factor
was
assumed
for
the
use
of
a
respirator
equipped
with
a
dust/
mist
filter.

Occupational
handler
exposure
assessments
are
completed
by
HED
using
different
levels
of
risk
mitigation.
Typically,
HED
uses
a
tiered
approach.
The
lowest
tier
is
designated
as
the
baseline
exposure
scenario
(
i.
e.,
long­
sleeve
shirt,
long
pants,
shoes,
socks,
and
no
respirator).
If
risks
are
of
concern
at
baseline
attire,
then
increasing
levels
of
personal
protective
equipment
or
PPE
(
e.
g.,
gloves,
double­
layer
body
protection,
and
respirators)
are
evaluated.
If
risks
remain
a
concern
with
maximum
PPE,
then
engineering
controls
(
e.
g.,
enclosed
cabs
or
cockpits,
water­
soluble
packaging,
and
closed
mixing/
loading
systems)
are
evaluated.
This
approach
is
used
to
ensure
that
the
lowest
level
of
risk
mitigation
that
provides
adequate
protection
is
selected,
since
the
addition
of
PPE
and
engineering
controls
involves
an
additional
expense
to
the
user
and
 
in
the
case
of
PPE
 
also
involves
an
additional
burden
to
the
user
due
to
decreased
comfort
and
dexterity
and
increased
heat
stress
and
respiratory
stress.

It
has
been
determined
that
exposure
to
pesticide
handlers
is
likely
during
the
occupational
use
of
MMA
or
DMA
on
agricultural
crops,
non­
crop
areas
and
on
turf
grass.
The
anticipated
use
patterns
and
current
labeling
indicate
occupational
exposure
scenarios
based
on
the
types
of
equipment
and
techniques
that
can
potentially
be
used
for
MMA
or
DMA
applications.
Risk
values
are
presented
for
each
route
of
exposure
(
i.
e.,
dermal
or
inhalation)
in
each
scenario,
because
risk
mitigation
measures
are
specific
to
the
route
of
exposure.
A
total
MOE
was
not
calculated
for
MMA
or
DMA
because
the
dermal
and
inhalation
toxicological
endpoints
of
concern
are
based
on
different
adverse
effects.
The
following
tables
present
the
risk
estimates
for
short
and
intermediate­
term
dermal
and
inhalation
exposures
at
baseline,
with
additional
personal
protective
equipment
(
PPE),
and
with
engineering
controls,
for
DMA,
CAMA
and
MSMA/
DSMA,
respectively.
Page
99
of
125
Table
9.1a:
Occupational
Handler
Short­
and
Intermediate­
term
Dermal
and
Inhalation
Exposure
and
Risks
to
DMA
MOEs
Baseline
PPE
Engineering
Controls
Exposure
Scenario
Crop
or
Target
Application
Rate
(
lb
ai/
A)
Area
Treated
Daily
(
acres)
Dermal
Inhalation
Dermal
 

single
layer
w/
gloves
Dermal
 

double
layer
w/
gloves
Inhalation
 

80%
Respirator
Dermal
Inhalation
Mixer/
Loader
Cotton
(
defoliation)
0.8
1200
7.5
270
950
1300
1300
2500
3800
Mixing/
Loading
Liquid
Concentrates
for
Aerial
Applications
(
1a)
Cotton
(
preconditioning
for
defoliation)
0.3
1200
20
710
2500
3400
3500
6800
10000
Cotton
(
defoliation)
0.8
200
45
1600
5700
7700
8000
15000
23000
Cotton
(
preconditioning
for
defoliation)
0.3
200
120
4300
15000
21000
21000
41000
62000
Non­
crop
7.3
100
9.9
350
1300
1700
1800
3300
5100
Mixing/
Loading
Liquids
Concentrates
for
Groundboom
Applications
(
1b)
Non­
bearing
citrus
orchards
4.96
80
18
640
2300
3100
3200
6200
9300
Lawn
edging
7.72
100
9.4
330
1200
1600
1700
3200
4800
Mixing/
Loading
Liquid
Concentrates
to
Support
LCO
Handgun
Applications
(
mixing/
loading
supports
20
LCOs)
(
1c)
Lawn
renovation
7.3
100
9.9
350
1300
1700
1800
3300
5100
Page
100
of
125
Table
9.1a:
Occupational
Handler
Short­
and
Intermediate­
term
Dermal
and
Inhalation
Exposure
and
Risks
to
DMA
MOEs
Baseline
PPE
Engineering
Controls
Exposure
Scenario
Crop
or
Target
Application
Rate
(
lb
ai/
A)
Area
Treated
Daily
(
acres)
Dermal
Inhalation
Dermal
 

single
layer
w/
gloves
Dermal
 

double
layer
w/
gloves
Inhalation
 

80%
Respirator
Dermal
Inhalation
Mixing/
Loading
Liquid
Concentrates
to
Support
Rights
of
Way
(
1d)
Non­
crop
7.3
80
12
440
1600
2100
2200
4200
6300
Applicator
Cotton
(
defoliation)
0.8
1200
No
Data
No
Data
No
Data
No
Data
No
Data
4400
4700
Applying
Sprays
via
Aerial
Equipment
(
2)
Cotton
(
preconditioning
for
defoliation)
0.3
1200
No
Data
No
Data
No
Data
No
Data
No
Data
12000
13000
Cotton
(
defoliation)
0.8
200
9400
2600
9400
12000
13000
26000
45000
Cotton
(
preconditioning
for
defoliation)
0.3
200
25000
6900
25000
32000
35000
70000
120000
Non­
crop
7.3
100
2100
570
2100
2600
2800
5800
9800
Applying
Sprays
via
Groundboom
Equipment
(
3)
Non­
bearing
citrus
orchards
4.96
80
3800
1000
3800
4800
5200
11000
18000
Lawn
edging
7.72
80
No
Data
350
100
180
1800
No
Data
No
Data
Applying
Sprays
via
Handgun
Equipment
(
4)
Lawn
renovation
7.3
80
No
Data
380
110
190
1900
No
Data
No
Data
Page
101
of
125
Table
9.1a:
Occupational
Handler
Short­
and
Intermediate­
term
Dermal
and
Inhalation
Exposure
and
Risks
to
DMA
MOEs
Baseline
PPE
Engineering
Controls
Exposure
Scenario
Crop
or
Target
Application
Rate
(
lb
ai/
A)
Area
Treated
Daily
(
acres)
Dermal
Inhalation
Dermal
 

single
layer
w/
gloves
Dermal
 

double
layer
w/
gloves
Inhalation
 

80%
Respirator
Dermal
Inhalation
Applying
Sprays
via
Rights
of
Way
Equipment
(
5)
Non­
crop
7.3
80
28
130
92
120
670
No
Data
No
Data
Flagger
Cotton
(
defoliation)
0.8
350
6800
3100
No
Data
7500
16000
340000
160000
Flagging
for
Aerial
Sprays
Applications
(
6)
Cotton
(
preconditio
ning
for
defoliation)
0.3
350
18000
8300
No
Data
20000
42000
910000
420000
Mixer/
Loader/
Applicator
Non­
bearing
citrus
orchards
4.96
5
56
4600
2600
No
Data
23000
NF
NF
Lawn
edging
7.72
5
36
2900
1600
No
Data
15000
NF
NF
Lawn
renovation
7.3
5
38
3100
1700
No
Data
16000
NF
NF
Mixing/
Loading/

Applying
Liquid
Concentrates
with
Low
Pressure
Handwand
(
ORETF)
(
7)
Non­
crop
7.3
5
38
3100
1700
No
Data
16000
NF
NF
Page
102
of
125
Table
9.1a:
Occupational
Handler
Short­
and
Intermediate­
term
Dermal
and
Inhalation
Exposure
and
Risks
to
DMA
MOEs
Baseline
PPE
Engineering
Controls
Exposure
Scenario
Crop
or
Target
Application
Rate
(
lb
ai/
A)
Area
Treated
Daily
(
acres)
Dermal
Inhalation
Dermal
 

single
layer
w/
gloves
Dermal
 

double
layer
w/
gloves
Inhalation
 

80%
Respirator
Dermal
Inhalation
Non­
bearing
citrus
orchards
4.96
5
No
Data
6900
1900
3500
34000
NF
NF
Lawn
edging
7.72
5
No
Data
4400
1200
2200
22000
NF
NF
Lawn
renovation
7.3
5
No
Data
4700
1300
2300
23000
NF
NF
Mixing/
Loading/

Applying
Liquid
Concentrates
with
a
Handgun
Sprayer
(
LCO
ORETF
data)
(
8)
Non­
crop
7.3
5
No
Data
4700
1300
2300
23000
NF
NF
Applying
Ready
to
Use
Formulations
via
Trigger­
Pump
Sprayer
(
ORETF)
(
9)
Non­
crop
0.00017
1000
3000
96000
70000
No
Data
480000
NF
NF
Lawn
edging
0.00018
1000
11000
100000
No
Data
No
Data
510000
NF
NF
Mixing/
Loading/

Applying
Liquids
with
a
Watering
Can
(
using
ORETF
residential
hoseend
data)
(
10)
Lawn
renovation
0.00017
1000
11000
110000
No
Data
No
Data
540000
NF
NF
Page
103
of
125
Table
9.1b:
Occupational
Handler
Short­
and
Intermediate­
term
Dermal
and
Inhalation
Exposure
and
Risks
to
CAMA
MOEs
Baseline
PPE
Engineering
Controls
Exposure
Scenario
Crop
or
Target
App
Rate
of
CAMA
(
lb
ai/
acre)
App
Rate
of
MMA
(
lb
ai/
acre)
Area
Treated
Daily
(
acres)
Dermal
Inh
Dermal
 

single
layer
w/
gloves
Dermal
 

double
layer
w/
gloves
Inhalation
 

80%
R
Dermal
Inh
Mixer/
Loader
Lawn
and
ornamental
turf
(
on
grasses
other
than
Bent)
5
4.4
40
140
1500
17000
23000
7300
46000
21000
Lawn
and
ornamental
turf
(
on
Bermuda
and
Zoysia
grass)
4.182
3.7
40
160
1700
21000
28000
8700
55000
25000
Mixing/
Loading
Liquids
Concentrates
for
Groundboom
Applications
(
1a)
Lawn
and
ornamental
turf
(
on
bentgrass)
2.5
2.2
40
270
2900
35000
47000
15000
92000
42000
Lawn
and
ornamental
turf
(
on
grasses
other
than
Bent)
5
4.4
100
55
580
6900
9400
2900
18000
8400
Lawn
and
ornamental
turf
(
on
Bermuda
and
Zoysia
grass)
4.182
3.7
100
66
690
8300
11000
3500
22000
10000
Mixing/
Loading
Liquid
Concentrates
for
LCO
Handgun
Applications
(
1b)
Lawn
and
ornamental
turf
(
on
bentgrass)
2.5
2.2
100
110
1300
14000
19000
5800
37000
17000
Page
104
of
125
Table
9.1b:
Occupational
Handler
Short­
and
Intermediate­
term
Dermal
and
Inhalation
Exposure
and
Risks
to
CAMA
MOEs
Baseline
PPE
Engineering
Controls
Exposure
Scenario
Crop
or
Target
App
Rate
of
CAMA
(
lb
ai/
acre)
App
Rate
of
MMA
(
lb
ai/
acre)
Area
Treated
Daily
(
acres)
Dermal
Inh
Dermal
 

single
layer
w/
gloves
Dermal
 

double
layer
w/
gloves
Inhalation
 

80%
R
Dermal
Inh
Applicator
Lawn
and
ornamental
turf
(
on
grasses
other
than
Bent)
5
4.4
40
28000
2400
28000
36000
12000
80000
40000
Lawn
and
ornamental
turf
(
on
Bermuda
and
Zoysia
grass)
4.182
3.7
40
34000
2800
34000
43000
14000
95000
48000
Applying
Sprays
via
Groundboom
Equipment
(
2)
Lawn
and
ornamental
turf
(
on
bentgrass)
2.5
2.2
40
57000
4700
57000
72000
24000
160000
81000
Lawn
and
ornamental
turf
(
on
grasses
other
than
Bent)
5
4.4
80
ND
620
580
1000
3100
NF
NF
Lawn
and
ornamental
turf
(
on
Bermuda
and
Zoysia
grass)
4.182
3.7
80
ND
740
700
1300
3700
NF
NF
Applying
Sprays
via
Handgun
Equipment
(
3)
Lawn
and
ornamental
turf
(
on
bentgrass)
2.5
2.2
80
ND
1200
1200
2100
6200
NF
NF
Page
105
of
125
Table
9.1b:
Occupational
Handler
Short­
and
Intermediate­
term
Dermal
and
Inhalation
Exposure
and
Risks
to
CAMA
MOEs
Baseline
PPE
Engineering
Controls
Exposure
Scenario
Crop
or
Target
App
Rate
of
CAMA
(
lb
ai/
acre)
App
Rate
of
MMA
(
lb
ai/
acre)
Area
Treated
Daily
(
acres)
Dermal
Inh
Dermal
 

single
layer
w/
gloves
Dermal
 

double
layer
w/
gloves
Inhalation
 

80%
R
Dermal
Inh
Mixer/
Loader/
Applicator
Lawn
and
ornamental
turf
(
on
grasses
other
than
Bent)
5
4.4
5
No
Data
7700
7100
13000
39000
NF
NF
Lawn
and
ornamental
turf
(
on
Bermuda
and
Zoysia
grass)
4.182
3.7
5
No
Data
9300
8500
16000
46000
NF
NF
Mixing/
Loading/
Applying
Liquid
Concentrates
with
a
Handgun
Sprayer
(
LCO
ORETF
data)

(
4)
Lawn
and
ornamental
turf
(
on
bentgrass)
2.5
2.2
5
No
Data
15000
14000
26000
77000
NF
NF
Page
106
of
125
Table
9.1c:
Occupational
Handler
Short­
and
Intermediate­
term
Dermal
and
Inhalation
Exposure
and
Risks
to
DSMA
MOEs
Baseline
PPE
Engineering
Controls
Exposure
Scenario
Crop
or
Target
App
Rate
of
DSMA
(
lb
ai/
acre)
App
Rate
of
MMA
(
lb
ai/
acre)
Area
Treated
Daily
(
acres)
Dermal
Inh
Dermal
 

single
layer
w/
gloves
Dermal
 

double
layer
w/
gloves
Inhalation
 

80%
R
Dermal
Inh
Mixer/
Loader
Mixing/

Loading
Liquid
Concentrates
for
Aerial
Applications
(
1a)
Cotton
(
pre­
plant
or
post­
plant
up
to
cracking)
2.268
1.7
1200
12
120
1500
2000
620
3900
1800
Cotton
(
postemergent
directed
spray)
2.268
1.7
200
70
740
8800
12000
3700
24000
11000
Grass
grown
for
seed
4.4
3.3
80
90
950
11000
15000
4800
30000
14000
Turf
for
sod
farms
3.293
2.5
80
120
1300
15000
21000
6400
41000
18000
Lawns
and
Ornamental
Turf
(
well
established
actively
growing
turf
grass)
3.293
2.5
80
120
1300
15000
21000
6400
41000
18000
Nonbearing
Fruit,
Nut,
&

Vineyards
4.85
3.7
80
82
870
10000
14000
4300
28000
13000
Mixing/

Loading
Liquids
Concentrates
for
Groundboom
Applications
(
1b)
Noncrop
Areas
5.1
3.88
100
62
660
7800
11000
3300
21000
9500
Page
107
of
125
Table
9.1c:
Occupational
Handler
Short­
and
Intermediate­
term
Dermal
and
Inhalation
Exposure
and
Risks
to
DSMA
MOEs
Baseline
PPE
Engineering
Controls
Exposure
Scenario
Crop
or
Target
App
Rate
of
DSMA
(
lb
ai/
acre)
App
Rate
of
MMA
(
lb
ai/
acre)
Area
Treated
Daily
(
acres)
Dermal
Inh
Dermal
 

single
layer
w/
gloves
Dermal
 

double
layer
w/
gloves
Inhalation
 

80%
R
Dermal
Inh
Mixing/

Loading
Liquid
Concentrates
to
Support
LCO
Handgun
Applications
(
mixing/
loading
supports
20
LCOs)
(
1c)
Lawns
and
Ornamental
Turf
(
well
established
actively
growing
turf
grass)
3.293
2.5
100
96
1000
12000
16000
5100
32000
15000
Mixing/

Loading
Liquid
Concentrates
to
Support
Rights
of
Way
(
1d)
Noncrop
Areas
5.1
3.88
80
78
820
9800
13000
4100
26000
12000
Applicator
Applying
Sprays
via
Aerial
Equipment
(
2)
Cotton
2.268
1.7
1200
No
Data
No
Data
No
Data
No
Data
No
Data
6800
2200
Cotton
2.268
1.7
200
14000
1200
14000
18000
6000
41000
21000
Grass
grown
for
seed
4.4
3.3
80
19000
1500
19000
24000
7700
52000
27000
Applying
Sprays
via
Groundboom
Equipment
(
3)
Turf
on
sod
farms
3.293
2.5
80
25000
2100
25000
32000
10000
70000
36000
Page
108
of
125
Table
9.1c:
Occupational
Handler
Short­
and
Intermediate­
term
Dermal
and
Inhalation
Exposure
and
Risks
to
DSMA
MOEs
Baseline
PPE
Engineering
Controls
Exposure
Scenario
Crop
or
Target
App
Rate
of
DSMA
(
lb
ai/
acre)
App
Rate
of
MMA
(
lb
ai/
acre)
Area
Treated
Daily
(
acres)
Dermal
Inh
Dermal
 

single
layer
w/
gloves
Dermal
 

double
layer
w/
gloves
Inhalation
 

80%
R
Dermal
Inh
Lawns
and
Ornamental
Turf
(
well
established
actively
growing
turf
grass­
golf
courses
3.293
2.5
40
50000
4100
50000
63000
21000
140000
71000
Nonbearing
Fruit
&
Nut
Orchards
&

Vineyards
4.85
3.7
80
17000
1400
17000
22000
7000
47000
24000
Applying
Sprays
via
Groundboom
Equipment,

Cont.
(
3)
Noncrop
Areas
5.1
3.88
100
13000
1100
13000
16000
5300
36000
18000
Applying
Sprays
via
Handgun
Equipment
(
4)
Lawns
and
Ornamental
Turf
(
well
established
actively
growing
turf
grass)
3.293
2.5
5
No
Data
17000
16000
29000
87000
NF
NF
Applying
Sprays
via
Rights
of
Way
Equipment
(
5)
Noncrop
Areas
5.10
3.88
80
170
250
580
780
1300
NF
NF
Flagger
Flagging
for
Aerial
Sprays
Applications
(
6)
Cotton
2.268
1.7
350
11000
1500
No
Data
12000
7300
530000
73000
Page
109
of
125
Table
9.1c:
Occupational
Handler
Short­
and
Intermediate­
term
Dermal
and
Inhalation
Exposure
and
Risks
to
DSMA
MOEs
Baseline
PPE
Engineering
Controls
Exposure
Scenario
Crop
or
Target
App
Rate
of
DSMA
(
lb
ai/
acre)
App
Rate
of
MMA
(
lb
ai/
acre)
Area
Treated
Daily
(
acres)
Dermal
Inh
Dermal
 

single
layer
w/
gloves
Dermal
 

double
layer
w/
gloves
Inhalation
 

80%
R
Dermal
Inh
Mixer/
Loader/
Applicator
Mixing/
Loading/

Applying
Liquid
Concentrates
with
Low
Pressure
Handwand
(
ORETF)
(
7)
Lawns
and
Ornamental
Turf
(
well
established
actively
growing
turf
grass)
3.293
2.5
5
280
6900
13000
No
Data
34000
NF
NF
Lawns
and
Ornamental
Turf
(
well
established
actively
growing
turf
grass)
3.293
2.5
5
No
Data
14000
12000
23000
68000
NF
NF
Mixing/
Loading/

Applying
Liquid
Concentrates
with
a
Handgun
Sprayer
(
LCO
ORETF
data)
(
8)
Nonbearing
Fruit
&
Nut
Orchards
&

Vineyards
4.85
3.7
5
No
Data
9200
8400
15000
46000
NF
NF
Page
110
of
125
Table
9.1d:
Occupational
Handler
Short­
and
Intermediate­
term
Dermal
and
Inhalation
Exposure
and
Risks
to
MSMA
MOEs
Baseline
PPE
Engineering
Controls
Exposure
Scenario
Crop
or
Target
App
Rate
of
MSMA
(
lb
ai/
acre)
App
Rate
of
MMA
(
lb
ai/
acre)
Area
Treated
Daily
(
acres)
Dermal
Inh
Dermal
 

single
layer
w/
gloves
Dermal
 

double
layer
w/
gloves
Inhalation
 

80%
R
Dermal
Inh
Mixer/
Loader
Cotton
(
pre­
plant
or
post­
plant
up
to
cracking)
2
1.7
1200
12
120
1500
2000
620
3900
1800
Mixing/
Loading
Liquid
Concentrates
for
Aerial
Applications
(
1a)
Cotton
(
postemergent
over
the
top
broadcast
spray)
0.9375
0.8
1200
25
260
3100
4200
1300
8400
3800
Cotton
(
postemergent
directed
spray)
2
1.7
200
70
740
8800
12000
3700
24000
11000
Cotton
(
postemergent
directed
band
application)
0.9375
0.8
200
150
1600
19000
25000
7900
50000
23000
Grass
grown
for
seed
6.16
5.3
80
57
600
7100
9700
3000
19000
8700
Turf
on
sod
farms
3.9204
3.4
80
89
940
11000
15000
4700
30000
14000
Mixing/
Loading
Liquids
Concentrates
for
Groundboom
Applications
(
1b)
Lawns
and
Ornamental
Turf
(
athletic
fields,
golf
courses,
parks)
2.6136
2.3
80
130
1400
17000
23000
7100
45000
20000
Page
111
of
125
Table
9.1d:
Occupational
Handler
Short­
and
Intermediate­
term
Dermal
and
Inhalation
Exposure
and
Risks
to
MSMA
MOEs
Baseline
PPE
Engineering
Controls
Exposure
Scenario
Crop
or
Target
App
Rate
of
MSMA
(
lb
ai/
acre)
App
Rate
of
MMA
(
lb
ai/
acre)
Area
Treated
Daily
(
acres)
Dermal
Inh
Dermal
 

single
layer
w/
gloves
Dermal
 

double
layer
w/
gloves
Inhalation
 

80%
R
Dermal
Inh
Lawns
and
Ornamental
Turf
(
established
Bermuda
grass
and
zoysia
grass
3.9204
3.4
80
89
940
11000
15000
4700
30000
14000
Nonbearing
Fruit,
Nut,
&

Vineyards
4
3.5
80
87
920
11000
15000
4600
29000
13000
Mixing/
Loading
Liquids
Concentrates
for
Groundboom
Applications,

Cont.
(
1b)
Noncrop
Areas
4.5
3.9
100
62
660
7800
11000
3300
21000
9500
Lawns
and
Ornamental
Turf
(
athletic
fields,
golf
courses,
parks)
2.6136
2.3
100
110
1100
13000
18000
5700
36000
16000
Lawns
and
Ornamental
Turf
(
well
established
actively
growing
turf
grass)
2.178
1.9
100
130
1400
16000
22000
6800
43000
20000
Mixing/
Loading
Liquid
Concentrates
to
Support
LCO
Handgun
Applications
(
mixing/
loadin
g
supports
20
LCOs)
(
1c)
Lawns
and
Ornamental
Turf
(
established
Bermuda­
grass
and
zoysia
grass
3.9204
3.4
100
71
750
9000
12000
3800
24000
11000
Page
112
of
125
Table
9.1d:
Occupational
Handler
Short­
and
Intermediate­
term
Dermal
and
Inhalation
Exposure
and
Risks
to
MSMA
MOEs
Baseline
PPE
Engineering
Controls
Exposure
Scenario
Crop
or
Target
App
Rate
of
MSMA
(
lb
ai/
acre)
App
Rate
of
MMA
(
lb
ai/
acre)
Area
Treated
Daily
(
acres)
Dermal
Inh
Dermal
 

single
layer
w/
gloves
Dermal
 

double
layer
w/
gloves
Inhalation
 

80%
R
Dermal
Inh
Mixing/

Loading
Liquid
Concentrates
to
Support
Rights
of
Way
(
1d)
Noncrop
Areas
4.5
3.9
80
78
820
9800
13000
4100
26000
12000
Applicator
Cotton
2
1.7
1200
No
Data
No
Data
No
Data
No
Data
No
Data
6700
2200
Applying
Sprays
via
Aerial
Equipment
(
2)
Cotton
0.9375
0.8
1200
No
Data
No
Data
No
Data
No
Data
No
Data
14000
4600
Cotton
2
1.7
200
14000
1200
14000
18000
6000
40000
21000
Cotton
0.9375
0.8
200
31000
2600
31000
39000
13000
86000
44000
Grass
grown
for
seed
6.16
5.3
80
12000
970
12000
15000
4900
33000
17000
Turf
on
sod
farms
3.9204
3.4
80
18000
1500
18000
23000
7600
52000
26000
Applying
Sprays
via
Groundboom
Equipment
(
3)
Lawns
and
Ornamental
Turf
(
athletic
fields,
golf
courses,
parks)
2.6136
2.3
40
55000
4600
55000
70000
23000
150000
79000
Page
113
of
125
Table
9.1d:
Occupational
Handler
Short­
and
Intermediate­
term
Dermal
and
Inhalation
Exposure
and
Risks
to
MSMA
MOEs
Baseline
PPE
Engineering
Controls
Exposure
Scenario
Crop
or
Target
App
Rate
of
MSMA
(
lb
ai/
acre)
App
Rate
of
MMA
(
lb
ai/
acre)
Area
Treated
Daily
(
acres)
Dermal
Inh
Dermal
 

single
layer
w/
gloves
Dermal
 

double
layer
w/
gloves
Inhalation
 

80%
R
Dermal
Inh
Lawns
and
Ornamental
Turf
(
well
established
actively
growing
turf
grass­
golf
courses)

(
MSMA)
2.178
1.9
40
66000
5500
66000
85000
28000
190000
95000
Lawns
and
Ornamental
Turf
(
established
Bermuda
grass
and
zoysia
grass­
golf
courses)
3.9204
3.4
40
37000
3100
37000
47000
15000
100000
53000
Nonbearing
Fruit
&
Nut
Orchards
&

Vineyards
4
3.5
80
18000
1500
18000
23000
7500
51000
26000
Applying
Sprays
via
Groundboom
Equipment,

Cont.
(
3)
Noncrop
Areas
4.5
3.9
100
13000
1100
13000
16000
5300
36000
18000
Page
114
of
125
Table
9.1d:
Occupational
Handler
Short­
and
Intermediate­
term
Dermal
and
Inhalation
Exposure
and
Risks
to
MSMA
MOEs
Baseline
PPE
Engineering
Controls
Exposure
Scenario
Crop
or
Target
App
Rate
of
MSMA
(
lb
ai/
acre)
App
Rate
of
MMA
(
lb
ai/
acre)
Area
Treated
Daily
(
acres)
Dermal
Inh
Dermal
 

single
layer
w/
gloves
Dermal
 

double
layer
w/
gloves
Inhalation
 

80%
R
Dermal
Inh
Lawns
and
Ornamental
Turf
(
athletic
parks,
golf
courses,
parks)
2.6136
2.3
5
No
Data
19000
18000
33000
97000
NF
NF
Lawns
and
Ornamental
Turf
(
well
established
actively
growing
turf
grass)
2.178
1.9
5
No
Data
23000
22000
39000
120000
NF
NF
Applying
Sprays
via
Handgun
Equipment
(
4)
Lawns
and
Ornamental
Turf
(
established
Bermuda
grass
and
zoysia
grass)
3.9204
3.4
5
No
Data
13000
12000
22000
65000
NF
NF
Applying
Sprays
via
Rights
of
Way
Equipment
(
5)
Noncrop
Areas
4.5
3.9
80
170
250
580
780
1300
NF
NF
Page
115
of
125
Table
9.1d:
Occupational
Handler
Short­
and
Intermediate­
term
Dermal
and
Inhalation
Exposure
and
Risks
to
MSMA
MOEs
Baseline
PPE
Engineering
Controls
Exposure
Scenario
Crop
or
Target
App
Rate
of
MSMA
(
lb
ai/
acre)
App
Rate
of
MMA
(
lb
ai/
acre)
Area
Treated
Daily
(
acres)
Dermal
Inh
Dermal
 

single
layer
w/
gloves
Dermal
 

double
layer
w/
gloves
Inhalation
 

80%
R
Dermal
Inh
Flagger
Cotton
2
1.7
350
11000
1400
No
Data
12000
7200
530000
72000
Flagging
for
Aerial
Sprays
Applications
(
6)
Cotton
0.9375
0.8
350
22000
3100
No
Data
25000
15000
1100000
150000
Mixer/
Loader/
Applicator
Lawns
and
Ornamental
Turf
(
athletic
fields,
golf
courses,
parks)
2.6136
2.3
5
360
8700
16000
No
Data
43000
NF
NF
Lawns
and
Ornamental
Turf
(
well
established
actively
growing
turf
grass)
2.178
1.9
5
430
10000
19000
No
Data
52000
NF
NF
Mixing/
Loading/
Applying
Liquid
Concentrates
with
Low
Pressure
Handwand
(
ORETF)
(
7)
Lawns
and
Ornamental
Turf
(
established
Bermuda
grass
and
zoysia
grass)
3.9204
3.4
5
240
5800
11000
No
Data
29000
NF
NF
Page
116
of
125
Table
9.1d:
Occupational
Handler
Short­
and
Intermediate­
term
Dermal
and
Inhalation
Exposure
and
Risks
to
MSMA
MOEs
Baseline
PPE
Engineering
Controls
Exposure
Scenario
Crop
or
Target
App
Rate
of
MSMA
(
lb
ai/
acre)
App
Rate
of
MMA
(
lb
ai/
acre)
Area
Treated
Daily
(
acres)
Dermal
Inh
Dermal
 

single
layer
w/
gloves
Dermal
 

double
layer
w/
gloves
Inhalation
 

80%
R
Dermal
Inh
Lawns
and
Ornamental
Turf
(
athletic
fields,
golf
courses,
parks)
2.6136
2.3
5
No
Data
15000
14000
25000
75000
NF
NF
Lawns
and
Ornamental
Turf
(
well
established
actively
growing
turf
grass)
2.178
1.9
5
No
Data
18000
17000
30000
90000
NF
NF
Lawns
and
Ornamental
Turf
(
established
Bermuda
grass
and
zoysia
grass)
3.9204
3.4
5
No
Data
10000
9200
17000
50000
NF
NF
Mixing/
Loading/
Applying
Liquid
Concentrates
with
a
Handgun
Sprayer
(
LCO
ORETF
data)

(
8)
Nonbearing
Fruit
&
Nut
Orchards
&

Vineyards
(
MSMA)
4
3.5
5
No
Data
9900
9000
17000
49000
NF
NF
Page
117
of
125
9.1.2
Summary
of
Occupational
Handler
Risk
Concerns
For
the
dermal
and
inhalation,
short­
and
intermediate­
term
exposure,
the
level
of
concern
(
LOC)
or
target
MOE
is
100.
The
calculated
dermal
and
inhalation
risks
were
not
combined
for
shortterm
or
for
intermediate
term
exposures
because
the
dermal
and
inhalation
endpoints
are
based
on
different
toxicological
effects.
There
are
no
occupational
handler
scenarios
for
MMA
or
DMA
that
have
risks
of
concern,
with
some
level
of
mitigation.

For
inhalation
exposure,
all
scenarios
for
all
the
organic
arsenical
active
ingredients
passed
at
the
baseline
level
of
mitigation.
For
dermal
exposure,
some
scenarios
resulted
in
risks
of
concern
at
the
baseline
level
of
mitigation,
but
were
not
of
concern
with
PPE
(
i.
e.,
single
layer
plus
gloves).
See
Smith
2006.

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

9.2
Occupational
Postapplication
Exposures
and
Risk
Estimates
HED
uses
the
term
"
postapplication"
to
describe
exposures
to
individuals
that
occur
as
a
result
of
being
in
an
environment
that
has
been
previously
treated
with
a
pesticide
(
also
referred
to
as
reentry
exposure).
HED
believes
that
there
are
distinct
job
functions
or
tasks
related
to
the
kinds
of
activities
that
occur
in
previously
treated
areas.
Job
requirements
(
e.
g.,
the
kinds
of
jobs
to
cultivate
a
crop),
the
nature
of
the
crop
or
target
that
was
treated,
and
how
the
chemical
residues
degrade
in
the
environment
can
cause
exposure
levels
to
differ
over
time.
Each
factor
has
been
considered
in
this
assessment.

9.2.1
Occupational
Postapplication
Scenarios,
Inputs,
and
Assumptions
Currently,
DMA
is
registered
for
use
on
cotton,
turf
grass
and
lawns.
CAMA
is
registered
for
use
on
turf
grass
and
lawns,
and
the
occupational
label
for
CAMA
prohibits
use
on
turf
being
grown
for
sale,
commercial
use
as
sod,
commercial
seed
production,
or
for
research
purposes.
MSMA
and
DSMA
uses
are
varied
as
it
can
be
used
on
agricultural
crops
(
i.
e.
cotton
and
sod
farms)
and
in
a
variety
of
other
outdoor
occupational
settings
(
i.
e.,
rights­
of­
way,
golf
course
turf).
As
a
result,
a
wide
array
of
individuals
can
potentially
be
exposed
by
working
in
areas
that
have
been
previously
treated.
HED
is
concerned
about
the
kinds
of
exposures
one
could
receive
in
the
workplace.

HED
uses
a
concept
known
as
the
transfer
coefficient
to
numerically
represent
the
postapplication
exposures
one
would
receive
(
generally
presented
as
cm2/
hour).
A
transfer
coefficient
is
a
measure
of
the
residue
transferred
from
a
treated
surface
to
a
person
who
is
doing
a
task
or
activity
in
a
treated
area.
These
values
are
the
ratio
of
an
exposure
for
a
given
task
or
activity
to
the
amount
of
pesticide
residue
on
treated
surfaces
available
for
transfer.
HED
has
developed
a
series
of
standard
transfer
coefficients
that
are
unique
for
variety
of
job
tasks
or
Page
118
of
125
activities
that
are
used
in
lieu
of
chemical­
and
scenario­
specific
data.
In
addition
to
transfer
coefficients,
occupational
postapplication
exposures
to
workers
are
estimated,
in
general,
using
transferable
turf
residue,
dislodgeable
foliar
residue
or
soil
transferable
residue
values.
Transferable
turf
residues
(
TTRs)
are
the
amounts
of
pesticide
available
on
the
turf
surface
that
can
potentially
be
transferred
to
the
skin
of
workers
who
contact
treated
turf.
TTRs
are
measured
using
techniques
that
specifically
determine
the
amount
of
residues
on
the
surface
treated
leaves
or
other
plant
surfaces.
In
order
to
define
the
amount
of
transferable
residues
to
which
individuals
can
be
exposed,
whenever
possible
HED
relies
on
chemical­
and
crop­
specific
studies.
However,
when
no
chemical­
and
crop­
specific
studies
are
available,
HED
uses
a
standard
modeling
approach
to
predict
transferable
residues
over
time
(
best
described
in
HED's
SOPs
for
Residential
Exposure
Assessment).

The
registrant
has
submitted
one
TTR
study
in
support
of
the
reregistration
of
MSMA,
titled
Determination
of
Transferable
Residues
from
Turf
Treated
with
Monosodium
Methanearsonate
(
MRID
No.
449589­
01).
In
a
memo
dated
February
9,
2000
(
USEPA:
Sandvig)
HED
denied
a
request
by
Luxenbourg­
Pamol,
Inc.
to
use
the
MSMA
turf
transferable
residue
data
as
surrogate
data
for
DMA.
The
assumption
that
DMA
has
the
same
transferability
as
MSMA
cannot
be
made
based
on
similar
chemical,
physical,
and
toxicological
properties.
Further,
the
dissipation
rates
of
MSMA
and
DMA
have
not
been
shown
to
be
the
same.
HED
still
agrees
with
this
decision.
As
a
result,
HED
has
used
the
MSMA
TTR
study
to
assess
occupational
postapplication
exposures
to
MSMA,
DSMA,
and
CAMA.
DMA
occupational
postapplication
exposures
were
evaluated
using
HED's
default
assumptions
that
20
percent
of
the
initial
application
is
available
for
transfer
on
day
0
(
i.
e.,
12
hours
after
application)
and
that
the
residue
dissipates
at
a
rate
of
10
percent
per
day.

Inhalation
exposures
are
thought
to
be
negligible
in
outdoor
postapplication
scenarios,
since
DMA
and
MMA
have
low
vapor
pressure
and
the
dilution
factor
outdoors
is
considered
infinite.

9.2.2
Summary
of
Occupational
Postapplication
Risk
Concerns
The
number
of
days
after
application
that
the
calculated
MOE
exceeds
the
target
MOE
is
0
(
i.
e.,
12
hours
following
application)
for
all
crops/
use
sites
for
DMA,
CAMA
and
MSMA/
DSMA,
except
for
the
application
of
DMA
to
turf.
For
lawn
applications
using
DMA,
the
calculated
MOEs
range
from
22
to
47
on
day
0
(
12
hours
following
application)
depending
on
the
application
rate
and
postapplication
task
being
performed.

To
refine
the
occupational
postapplication
risk
assessment,
data
on
actual
use
patterns
including
rates,
timing,
and
the
kinds
of
tasks
that
are
required
to
produce
agricultural
commodities
and
other
products
would
better
characterize
MMA
and
DMA
risks
Page
119
of
125
Table
9.2.2a:
Summary
of
DMA
Occupational
Postapplication
Risks
Crop
Grouping
Application
rate
(
lb
ai/
acre)
Transfer
Coefficient
Day
after
Application
when
MOE
 
100
MOE
at
Day
0
1500
12
hours
3300
0.8
2500
12
hours
8700
1500
12
hours
2000
Cotton
0.3
2500
12
hours
5200
3400
8
45
7.7
6800
14
22
3400
7
47
Turf
7.3
6800
13
24
Table
9.2.2b:
Summary
of
CAMA
Occupational
Postapplication
Risks
Crop
Grouping
Application
rate
(
lb
ai/
acre)
Transfer
Coefficient
Day
after
Application
when
MOE
 
100
MOE
at
Day
0
3400
12
hours
260
5
6800
12
hours
130
3400
12
hours
310
4.182
6800
12
hours
160
3400
12
hours
520
Turf
2.5
6800
12
hours
260
Table
9.2.2c:
Summary
of
DSMA
Occupational
Postapplication
Risks
Crop
Grouping
Application
rate
(
lb
ai/
acre)
Transfer
Coefficient
Day
after
Application
when
MOE
 
100
MOE
at
Day
0
100
12
hours
23,000
1500
12
hours
1500
Cotton
2.268
2500
12
hours
900
3400
12
hours
460
Turf
3.293
6800
12
hours
230
Page
120
of
125
Table
9.2.2d:
Summary
of
MSMA
Occupational
Postapplication
Risks
Crop
Grouping
Application
rate
(
lb
ai/
acre)
Transfer
Coefficient
Day
after
Application
when
MOE
 
100
MOE
at
Day
0
100
12
hours
23,000
1500
12
hours
17,000
2
2500
12
hours
10,000
100
12
hours
24,000
1500
12
hours
18,000
1.875
2500
12
hours
11,000
100
12
hours
48,000
1500
12
hours
36,000
Cotton
0.9375
2500
12
hours
22,000
3400
12
hours
340
3.9204
6800
12
hours
170
3400
12
hours
510
2.6136
6800
12
hours
250
3400
12
hours
610
6800
12
hours
300
Turf
2.178
6800
12
hours
230
.

10.0
Data
Needs
and
Label
Requirements
10.1
Product
Chemistry
See
Tables
2.3a­
i
Product
Chemistry
Data
Summary
for
data
needs.

10.2
Residue
Chemistry
Speciated
(
MMA,
DMA,
iAs)
food
monitoring
data
are
needed.
The
current
enforcement
method
does
not
speciate
the
residues.
However,
a
submitted
analytic
method
(
in
review)
may
be
adequate
for
this
purpose.

10.3
Occupational/
Residential
Exposure
Studies
are
needed
to
better
analyze
build­
up
of
arsenic
(
organic
and
inorganic)
in
soils,
as
well
as
a
DMA
TTR
study.
Guidelines
for
these
studies
can
be
found
below.

In
Series
875
­
Group
B:
Postapplication
Exposure
Monitoring
Guidelines
:

Guideline
875.2100
=
Transferable
residue
dissipation:
Lawn
and
Turf
(
DMA
only).
Page
121
of
125
Guideline
875.2200
=
Soil
Residue
Dissipation
Guideline
875.2000
=
Study
Design
(
site
selection
considerations,
number
of
samples
and
replicates
and
test
safety,
materials
and
methods,
sample
handling
and
collection,
analytical
chemistry,
and
QA/
QC).
Page
122
of
125
11.0
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Benchmark
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USEPA
2000b.
Request
to
Use
MSMA
Turf
Transferable
Residue
Data
as
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Data
for
Cacodylic
Acid
and
Sodium
Cacodylate
in
Lieu
of
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(
PC
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012501
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DP
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258787).
Renee
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9,
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USEPA
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2005.

USEPA
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risk
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EPA/
630/
P­
03/
001FMarch
2005
U.
S.
Environmental
Protection
Agency
Washington,
DC
USEPA
2006.
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Mode
of
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for
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DMAV)
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Response
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January
30,
2006.

Yamamoto,
S.,
Konishi,
Y.,
Matsuda,
T.,
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Shibata,
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with
five
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1271 
1275
Yamamoto,
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Wanibuchi,
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353­
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Wei,
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Wanibuchi,
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(
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12.0
Attachments
Allen
2000a.
Review
of
Cacodylic
Acid
Poisoning
Incident
Data.
Ruth
Allen.
February
17,
2000.

Allen
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Review
of
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DSMA
Poisoning
Incident
Data.
Chemical:
#
013803/
013802,
DP
Barcode:
D265816.
Ruth
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September
22,
2000.

Allen
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Acid
Methanearsonate
(
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Chemical#
013806.
Ruth
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March
23,
2001.

Barnes
2006a.
Cacodylic
Acid/
Sodium
Cacodylate.
PC
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012501
&
012502.
List
B
Reregistration
Case
2080.
Product
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for
the
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Eligibility
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DP
Barcode
D251099.
P.
Yvonne
Barnes.
January
31,
2006.

Barnes
2006b.
Methanearsonic
Acid
(
MAA)
and
Salts
[
MSMA/
DSMA]
Product
Chemistry
Chapter
for
the
Reregistration
Eligibility
Decision
[
RED].
DP
Barcode:
D325973.
PC
Code(
s):
013802
and
013803.
P.
Yvonne
Barnes.
January
31,
2006.

Barnes
2006c.
Calcium
Acid
Methanearsonate
(
CAMA)
Product
Chemistry
Chapter
for
the
Reregistration
Eligibility
Decision
[
RED]
Document.
DP
Barcode:
D325973.
PC
Code:
013806.
P.
Yvonne
Barnes.
January
31,
2006.

Barnes/
Cropp­
Kohlligian
2006.
Residue
Chemistry
Chapter
for
the
Cacodylic
Acid
and
Salts
Reregistration
Eligibility
Decision
(
RED)
Document.
DP
Barcode:
D251054.
PC
Codes:
012501,
012502,
and
012503.
Reregistration
Case:
2080.
P.
Yvonne
Barnes/
Bonnie
Cropp­
Kohlligian.
January
31,
2006.

Barnes/
Kinard
2006.
Residue
Chemistry
Chapter
for
the
Monosodium
and
Disodium
Salts
of
Methanearsonic
Acid
(
PC
codes
013802
and
013803)
Reregistration
Eligibility
Decision
(
RED);
DP
Barcode
D275600;
Reregistration:
Case
Number
2395.
P.
Yvonne
Barnes/
Sherrie
Kinard.
January
31,
2006.

Carter
2005a.
Usage
Report
in
Support
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