Document ID: EPA-HQ-OPP-2006-0201-0077
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-08-09T04:00Z

Page
1
of
16
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
June
21,
2006
MEMORANDUM
SUBJECT:
RESPONSE
TO
PUBLIC
COMMENTS.
The
Health
Effects
Division's
Response
to
Comments
on
EPA's
Phase
3
Reregistration
Eligibility
Decision
Document
for
the
Organic
Arsenic
Herbicides
(
OPP
Docket#
OPP­
2006­
0201).
PC
Code:
012501,
013802,
013803,
and
013806;
DP
Barcode
D329697.

FROM:
Charles
Smith
Risk
Assessor/
ORE
Assessor
Reregistration
Branch
II
Health
Effects
Division
(
7509P)

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

TO:
Lance
Wormell,
Chemical
Review
Manager
Reregistration
Branch
II
Special
Review
and
Reregistration
Division
(
7508P)

The
attached
document
titled,
"
HED's
Response
to
Comments
on
EPA's
Phase
3
Reregistration
Eligibility
Decision
Document
for
the
Organic
Arsenic
Herbicides"
was
generated
in
the
Phase
4
period
of
the
Proposed
Public
Participation
Process
to
address
comments
submitted
by
The
Scotts
Company
LLC;
The
Golf
Course
Superintendents
Association
of
America
(
GCSAA);
The
Wood
Preservative
Science
Council
(
WPSC);
The
MAA
Research
Task
Force
which
consists
of
APC
Holdings
Company/
Drexel
Chemical
Company,
KMG­
Bernuth,
and
Luxembourg­
Pamol,
Inc.;
The
Florida
Department
of
Agriculture
and
Consumer
Services
(
FDACS);
and
private
citizens
to
the
Agency
following
the
publication
of
the
Agency's
Phase
3
Reregistration
Eligibility
Decision
(
RED)
Document
for
the
Organic
Arsenic
Herbicides
in
the
Federal
Register
April
5,
2006.
The
attached
document
is
the
HED's
response
to
those
comments.
This
response
includes
input
from
Page
2
of
16
Anna
Lowit
(
Toxicology),
Keara
Moore
(
Environmental
Fate),
Sherrie
Kinard
(
Residue
Chemistry
and
Dietary
Exposure)
and
Charles
Smith
(
Occupational
and
Residential
Exposure/
Risk
Assessment).

cc:
Debbie
Edwards
Margaret
Rice
Dirk
Helder
William
Hazel
Jack
Housenger
Tina
Levine
Page
3
of
16
TABLE
OF
CONTENTS
I.
Introduction.........................................................................................................
Page
4
of
16
II.
Toxicology.........................................................................................................
Page
4
of
16
III.
Dietary
Exposure
..............................................................................................
Page
9
of
16
IV.
Occupational
and
Residential
Exposures...........................................................
Page
14
of
16
Page
4
of
16
HED'S
RESPONSE
TO
COMMENTS
FOR
THE
ORGANIC
ARSENIC
HERBICIDES
I.
Introduction
The
following
is
HED's
response
to
comments
on
the
Phase
3
Reregistration
Eligibility
Document
(
RED)
for
the
organic
arsenic
herbicides,
generated
in
response
to
the
comments
submitted
to
the
public
docket
by
the
registrants,
consumer
groups,
and
environmental
advocacy
groups
to
the
Agency
following
the
publication
of
the
preliminary
risk
assessment
(
Phase
3)
on
the
organic
arsenic
herbicides
in
the
Federal
Register
April
5,
2006
to
begin
Phase
4
of
the
Public
Participation
Process.
Some
of
the
responses
serve
as
clarification
or
a
restatement
of
Agency
policies
and
guidance
and
it
is
hoped
that
this
will
provide
a
greater
understanding
of
the
Agency's
position
and
procedures
on
these
matters.
Comments
concerning
the
rationale
behind
Agency
decisions,
toxicology,
exposure
assessment,
and
interpretation
of
available
data,
were
submitted.
Since
there
were
a
number
of
comments
submitted
from
very
differing
sources,
HED's
responses
will
be
directed
to
the
issues
raised
and
not
to
each
of
the
commentors.
In
many
cases,
the
same
subject
matter
was
raised
by
more
than
one
of
the
commentors
but
with
different
view
points.

Several
issues
related
to
the
availability/
efficacy
of
substitute
pesticides,
the
environmental
fate
and
persistence
of
the
organic
arsenic
herbicides,
wildlife
incidents,
and
the
generation
of
drinking
water
estimates,
were
raised
in
the
comments
and
will
be
addressed
in
separate
documents
by
the
appropriate
divisions:
the
Biological
and
Economics
Assessment
Division
(
BEAD)
and
the
Ecological
Fate
and
Effects
Division
(
EFED).

II.
Toxicology
There
are
several
public
comments
related
to
the
inorganic
arsenic
slope
factor.
These
include:

A.
The
MAA
Research
Task
Force
states:
Use
of
a
linear
extrapolation
with
an
unpublished
cancer
slope
factor
of
3.36
mg/
kg­
day­
1
for
low
doses
of
inorganic
arsenic
is
not
scientifically
warranted
or
defensible.
Based
on
extensive
evidence,
both
mechanistic
and
epidemiological,
there
is
scientific
consensus
that
arsenic's
dose­
response
is
likely
nonlinear.
The
EPA
Science
Advisory
Board's
Arsenic
Review
Panel,
which
is
re­
evaluating
the
carcinogenic
potency
of
inorganic
arsenic
and
the
dose­
response
relationship
for
arsenic­
induced
cancer,
has
concluded
that
"[
a]
t
present
the
experimental
evidence
on
mode
of
action
of
inorganic
arsenic
supports
a
possible
non­
linear
dose­
response
at
low
exposure
levels
.
.
.
."
Past
reviews
of
arsenic
carcinogenicity
also
have
suggested
the
dose­
response
for
arsenic
is
likely
nonlinear
and
that
linear
extrapolation
from
high­
dose
data
sets,
such
as
those
from
Taiwan,
overestimate
risks
in
the
U.
S.

In
view
of
the
considerable
available
evidence
from
epidemiologic
and
mechanistic
studies
that
support
a
nonlinear
dose­
response
for
inorganic
arsenic,
and
possibly
even
a
hormetic
effect,
Page
5
of
16
the
appropriate
and
scientifically
defensible
approach
is
to
use
a
margin
of
exposure
(
MOE)
analysis
to
characterize
cancer
risks
from
inorganic
arsenic.
The
MOE
should,
for
the
point
of
departure
(
POD),
use
the
threshold
dose
level
developed
from
epidemiological
studies,
i.
e.,
the
dose
level
at
which
there
is
no
observed
increase
in
cancer.
A
no
effect
level
of
ingested
inorganic
arsenic
of
0.013
mg/
kg­
day
should
be
used
as
a
POD
in
the
MOE
analysis.
As
detailed
in
Attachment
3,
assuming
non­
linearity
at
low
doses
and
using
a
MOE
approach
yields
an
aggregate
MOE
for
lifetime
exposure
to
inorganic
arsenic
of
53,
which
is
above
EPA's
level
of
concern.

B.
The
MAATF
further
states:
For
the
risk
assessment
to
be
legally
and
scientifically
defensible,
EPA
must
rely
on
available
epidemiological
data
and
utilize
a
MOE
approach
that
uses
a
no
observable
adverse
effect
level
of
0.013
mg/
kg­
day
for
bladder
cancer
incidence
in
a
susceptible
population
exposed
to
inorganic
arsenic,
as
discussed
more
fully
in
Attachment
3.
Using
realistic
estimates
that
aggregate
the
amount
of
inorganic
arsenic
in
food
and
water,
as
well
as
worst­
case
estimates
of
the
amount
of
inorganic
arsenic
in
soil
from
methylated
arsenic
herbicide
use,
MOEs
for
lifetime
exposure
to
inorganic
arsenic
are
above
a
level
of
concern.

C.
The
Wood
Preservative
Science
Council
(
WPSC)
believes
the
available
scientific
data
support
a
threshold
for
carcinogenicity,
particularly
at
levels
of
concern
to
the
U.
S.
population,
which
would
support
the
use
of
a
margin
of
exposure
approach
in
the
arsenic
risk
assessment.
In
fact,
EPA
specifically
requested
review
of
the
current
science
and
approach
by
the
Science
Advisory
Board
(
SAB).
The
SAB
is
still
in
the
process
of
providing
recommendations
to
the
Agency
but
draft
comments
clearly
suggest
that
the
Agency
needs
to
reconsider
the
available
science
and
how
it
is
interpreted
in
relation
to
potential
health
effects
of
inorganic
arsenic.

While
recognizing
that
the
SAB
report
has
not
yet
been
finalized,
the
following
comments
suggest
that
the
Agency
has
been
premature
in
its
characterization
of
the
potential
health
concerns
of
inorganic
arsenic
in
its
dietary
risk
assessment
of
the
organic
arsenic
herbicides.

 
If
arsenic
is
essential
for
humans
and/
or
if
epidemiological
data
could
be
strengthened
at
the
low­
dose
range
to
demonstrate
either
a
low­
dose
benefit
or
no
effect
at
low
dose,
then
a
threshold
is
certain.
However,
at
this
time,
the
data
are
lacking
or
problematic
with
regard
to
low­
dose
effects.
 
The
Panel
suggests
that
results
on
bladder
cancer
risk
from
published
epidemiology
studies
of
US
and
other
populations
chronically
exposed
to
0.5
to
160
µ
g/
L
inorganic
arsenic
in
drinking
water
be
critically
evaluated.
 
Aggregate
results,
particularly
on
bladder
cancer
risk,
from
multiple
published
epidemiology
studies
of
low
level
arsenic­
exposed
populations
need
to
be
taken
into
consideration
in
a
more
formal
secondary
integrative
analysis
and
compared
with
the
main
analysis
for
concordance.
Data
from
the
epidemiologic
studies
of
Page
6
of
16
relatively
low
exposure
can
be
informative
and
need
to
be
formally
evaluated
beginning
with
a
comparative
analysis
of
strengths
and
weaknesses
as
described
above.
 
The
current
cancer
risk
assessment
methodology
for
iAs
relies
on
choosing
a
single
epidemiological
study
to
derive
a
cancer
slope
factor
that
is
then
used
to
extrapolate
health
effects
considerably
below
the
exposure
levels
observed
in
that
study.
There
are
a
number
of
arsenic
epidemiology
studies
now
available
and
there
are
published
methods
for
quantitatively
integrating
results
from
multiple
studies
(
Coull
et
al.,
2003;
Ryan,
2005).
 
Integrative
analyses
result
in
improved
statistical
power
and
precision
of
the
estimates
that
represent
an
additional
advantage
of
utilizing
a
larger
dataset,
as
has
been
pointed
out
for
the
Taiwan
dataset.
Although
the
"
low"
arsenic
exposure
epidemiology
studies
cannot
by
themselves
provide
a
basis
for
doseresponse
modeling
because
of
lack
of
data
at
the
higher
exposure
levels,
they
do
provide
data
on
the
relative
risks
of
bladder
cancer
for
humans
exposed
at
low
levels.

HED
response
to
inorganic
arsenic
slope
factor
questions:
The
Agency's
2005
cancer
guidelines
describes
a
process
by
which
tumor
and
mechanistic
data
are
first
analyzed
to
evaluate
the
extent
to
which
there
is
a
sufficient
understanding
the
mode
of
action
for
the
agent
of
interest.
This
`
data
first­­
defaults
second'
paradigm
represents
the
Agency's
new
approach
for
cancer
risk
assessment.
In
the
case
of
DMA,
the
Agency
has
developed
a
mode
of
action
analysis
which
was
supported
by
the
SAB.
The
SAB
further
supported
a
non­
linear
cancer
risk
assessment
for
DMA.

As
described
in
the
Agency's
documentation
presented
to
the
SAB
in
2005,
the
mode(
s)
of
action
for
inorganic
arsenic
have
not
yet
been
elucidated.
In
accordance
with
the
cancer
guidelines,
for
chemicals
whose
mode
of
action
is
not
yet
understood,
the
Agency
must
use
a
linear
extrapolation
in
its
cancer
risk
assessment.
At
the
September,
2005
SAB
meeting,
the
Agency
presented
the
proposed
approaches
for
addressing
revisions
to
the
inorganic
arsenic
slope
factor
based
on
the
National
Academy
of
Sciences
report.
The
Agency
is
considering
the
comments
of
the
SAB
in
its
revised
slope
factor.
At
this
time,
OPP
will
continue
to
use
the
published
value
of
3.67.

Regarding
the
actual
slope
factor
used
by
HED
in
its
risk
assessment,
OPP
has
applied
3.67
which
is
the
same
factor
as
that
used
in
the
risk
assessment
for
arsenic
treated
wood
and
in
the
EPA's
Office
of
Water
rule
on
the
MCL
for
arsenic.
OPP's
March
2006
risk
assessment
incorrectly
applied
3.36.
This
has
been
corrected
in
the
current
document.

Regarding
the
short­
term
incidental
oral
endpoint
the
MAA
Research
Task
Force
states
that
EPA
incorrectly
uses
the
benchmark
dose
level
from
a
10­
week
rat
carcinogenicity
study
­­
a
chronic
study
­­
as
the
toxicity
endpoint
for
assessing
acute
DMA
risks.
Sound
science,
however,
mandates
that
EPA
assess
acute
risks
by
relying
on
available
acute
studies,
in
this
case
acute
Page
7
of
16
developmental
studies
in
rats
and
rabbits
that
better
characterize
the
possible
adverse
effects
during
the
relevant
exposure
period.
Reliance
on
the
acute
rat
and
rabbit
studies
results
in
an
approximately
28­
fold
increase
in
all
residential
short­
term
MOEs,
a
dramatic
difference
that
demonstrates
the
need
to
correct
the
study
EPA
uses
to
ensure
a
scientifically
defensible
risk
assessment
(
see
Attachment
11)."

HED
response
short­
term
incidental
oral
endpoint:
As
described
in
the
Agency's
mode
of
action
paper
for
DMA,
increased
regenerative
proliferation
has
been
noted
as
early
as
1
week
of
exposure
at
100
ppm
(
Cohen
et
al,
2001).
Dose­
response
data
are
available
only
at
week
10.
HED
defines
short­
term
incidental
oral
exposures
to
range
from
1
to
30
days.
In
the
absence
of
dose
response
data
of
shorter
duration,
it
is
reasonable
to
use
regenerative
proliferation
at
10
weeks
of
exposure.
Shorter
term
incidental
oral
exposure
is
not
considered
to
be
acute
(
i.
e.,
single
day)
exposure.
Instead,
OPP
assumes
that
a
child
may
be
exposed
on
repeated
days
to
treated
grass.
Thus,
the
study
used
to
estimate
acute
dietary
exposure
is
not
appropriate
for
short­
term
incidental
oral
exposure.

Regarding
direct
exposure
to
the
trivalent
species
of
MMA
and
DMA,
the
Florida
Department
of
Agriculture
and
Consumer
Services
(
FDACS)
is
concerned
that
exposure
may
be
to
the
more
toxic,
trivalent,
forms
of
MMA
and
DMA.

HED
&
EFED
response:
Limited
data
are
available
regarding
the
potential
for
transformation
of
organic
arsenicals
from
the
pentavalent
state
to
the
trivalent
state.
Recent
laboratory
studies
have
observed
significant
transformation
of
MMAV
to
MMAIII
in
anaerobic
sludges
that
are
methanogenic
or
sulfate­
reducing
(
Sierra­
Alvarez
et
al,
2006).
In
the
environment,
this
type
of
reaction
would
only
be
expected
to
occur
in
the
reducing
conditions
of
anoxic
soils
and
sediments.
Anoxic
soils
normally
occur
because
of
the
sustained
presence
of
water,
as
in
saturated
subsoils
at
or
below
the
water
table
and
surface
soils
in
wetlands.
These
conditions
are
unlikely
to
occur
in
typical
surface
soils
in
residential
areas
and
other
areas
where
turf
is
grown.
Thus,
the
Agency
believes
that
when
MMA
and
DMA
are
applied
in
residential
settings
exposure
is
to
the
pentavalent
forms.

Outside
of
these
turf
areas,
there
are
some
anoxic
environmental
conditions
in
which
transformation
of
pentavalent
to
trivalent
arsenicals
may
occur,
but
these
conditions
are
localized.
Additionally,
there
is
the
possibility
that
any
trivalent
arsenicals
may
be
oxidized
back
to
the
pentavalent
form
when
transported
away
from
these
conditions,
prior
to
reaching
surface
water.
The
Agency
believes
that
any
aquatic
exposure
to
arsenicals
is
also
primarily
to
the
pentavalent
form.

There
were
some
comments
from
FDACS
and
from
the
Florida
Department
of
Environmental
Protection
pertaining
to
the
cancer
classification
of
the
organic
arsenicals
and
the
uncertainty
associated
with
inorganic
arsenic
as
a
human
carcinogen.
Page
8
of
16
A.
The
FDACS
states
that
"
With
this
risk
assessment,
the
EPA
has
changed
its
classification
of
the
organic
arsenical
herbicides
from
that
of
probable
or
possible
carcinogens
(
EPA,
1995)
to
not
likely
to
be
human
carcinogens,
despite
the
fact
that
the
ultimate
carcinogenic
metabolite
responsible
for
causing
cancer
has
not
yet
been
identified.
Furthermore,
we
know
that
inorganic
arsenic
is
carcinogenic
only
from
human
epidemiological
studies,
since
inorganic
arsenic
does
not
cause
cancer
in
animals.
Yet,
we
have
no
human
data
for
the
carcinogenicity
of
organic
arsenical
herbicides,
but
we
do
know
that
some
forms
(
e.
g.,
DMA)
do
cause
cancer
in
animals
(
Goering
et
al
.,
1999).
The
evidence
that
humans
are
particularly
sensitive
to
inorganic
arsenic
compared
to
most
other
animals
that
have
been
studied
(
Goering
et
al
.,
1999);
the
high
degree
of
risk
associated
with
inorganic
arsenic;
and
the
uncertainty
of
the
various,
continually
changing
forms
of
arsenicals
to
which
people
may
be
exposed
under
numerous
possible
environments
(
e
.
g.,
organic
vs.
inorganic,
pentavalent
vs.
.
trivalent),
argues
that
a
conservative
approach
be
taken
in
the
assessment
of
the
organic
arsenical
herbicides."

B.
The
Florida
Department
of
Environmental
Protection
states
that
the
characterization
of
the
toxicities
of
the
various
arsenical
compounds
fails
to
acknowledge
certain
uncertainties.
The
most
important
uncertainty
deals
with
cancer
risks.
Carcinogenicity
for
MMA
and
DMA
is
dismissed
because
only
DMA
produced
a
carcinogenic
response
in
rodents,
and
the
mode
of
action
for
this
effect,
while
germane
to
humans,
is
thought
to
be
relevant
only
at
high
doses
producing
enhanced
cell
proliferation
in
the
bladder.
An
unanswered
question
is
whether
DMA
(
and
MMA)
might
also
have
carcinogenic
potential
through
the
same
mode
of
action
as
inorganic
arsenic.
This
question
can't
be
answered
from
animal
studies
because
the
mode
of
action
is
absent
 
inorganic
arsenic
is
essentially
negative
in
rat
and
mouse
studies.
If
inorganic
arsenic,
a
known
human
carcinogen,
is
negative
in
rat
and
mouse
studies,
what
conclusions
can
be
drawn
when
other
arsenicals
are
also
negative?
In
the
absence
of
a
positive
indication
of
carcinogenicity
of
MMA,
and
something
from
DMA
other
than
the
rat
bladder
tumors,
the
HED
has
no
choice
to
evaluate
MMA
and
DMA
direct
exposure
risks
on
effects
other
than
cancer.

HED
response:
The
Agency
presented
an
issue
paper
describing
aspects
of
the
metabolism
and
toxicity
of
inorganic
and
organic
arsenical
compounds
to
the
Science
Advisory
Board
in
2005.
The
SAB
supported
the
Agency's
position
that
the
cancer
potential
for
the
arsenicals
should
be
evaluated
based
on
data
related
to
the
specific
chemical.
The
SAB
further
supported
the
Agency's
mode
of
action
analysis
for
DMA
and
supported
non­
linear
cancer
risk
extrapolation
for
DMA.
The
Agency
believes
its
current
risk
assessment
is
based
on
the
best
available
science
and
is
protective
of
human
health.
Page
9
of
16
III.
Dietary
Exposure
The
MAA
Research
Task
Force
states
all
available
data
show
that
inorganic
arsenic
comprises
only
a
very
small
fraction
of
total
dietary
arsenic,
yet,
EPA
uses
total
arsenic
as
a
surrogate
for
inorganic
arsenic
intake
levels.
EPA
must
instead
calculate
risks
for
the
predicted
levels
of
inorganic
arsenic
residues
based
on
available,
relevant
data.

EPA
relies
on
the
FDA
TDS
to
determine
the
potential
dietary
exposure
to
arsenic.
The
TDS
does
not
distinguish
between
the
different
compounds
of
arsenic.
Thus,
EPA
uses
total
arsenic
in
the
diet
to
assess
potential
dietary
risks
from
inorganic
arsenic.
Foods
contain
various
arsenic
compounds,
including
arsenosugars,
arsenobetaine,
MMA,
DMA,
inorganic
arsenic,
and
others.
Each
of
these
compounds
has
a
unique
toxicity,
hence
it
is
essential
to
quantify
the
actual
amount
of
each
specific
arsenic
compound
to
accurately
evaluate
risk.
The
assumption
that
total
arsenic
in
food
exists
entirely
as
one
species
ignores
the
current
scientific
knowledge
that
different
arsenic
compounds
have
different
toxicities,
and
thus
generates
erroneous
risk
estimates.

In
fact,
the
issue
has
been
recognized
by
EPA,
and
EPA's
National
Exposure
Research
Laboratory
(
NERL)
has
initiated
a
research
program
to
improve
the
analytical
techniques
for
the
determination
of
specific
arsenic
compounds
in
foods.
While
the
NERL
analysis
is
not
yet
completed,
there
are
numerous
publications
that
report
analysis
of
arsenic
species
in
food,
as
outlined
in
Attachment
2
to
this
letter.
One
critical
example
is
the
published
market
basket
survey
by
Schoof
et
al.,
which
determines
the
relative
proportion
of
inorganic
arsenic
in
food.
The
survey
was
designed
to
analyze
specific
arsenic
species
in
those
foods
expected
to
contribute
90%
of
the
inorganic
arsenic
in
the
U.
S.
diet.
The
Schoof,
et
al.
data
conclusively
demonstrate
that
inorganic
arsenic
represents
only
a
small
fraction
of
the
total
arsenic
in
food.
Moreover,
the
Schoof,
et
al.
data,
combined
with
consumption
information
from
the
U.
S.
Department
of
Agriculture's
(
USDA)
County
Surveys
of
Food
Intake
by
Individuals
for
1989­
1992,
show
that
the
mean
dietary
arsenic
intake
from
the
U.
S.
diet
is
less
than
10%
of
total
dietary
intake
EPA
uses
in
the
risk
assessment.

In
summary,
the
risk
assessment
greatly
overestimates
dietary
intake
of
inorganic
arsenic.
Use
of
the
available
relevant
data
show
that
there
should
be
a
decrease
of
at
least
17.5­
fold
in
inorganic
arsenic
dietary
intake
that
the
current
risk
assessment
estimates,
which
are
based
on
data
and
assumptions
that
are
not
relevant
to
the
organic
arsenic
herbicides.
EPA
must
correct
these
assumptions
to
ensure
that
the
risk
assessment
is
scientifically
and
legally
defensible.

HED
Answer:
The
dietary
risk
assessment
does
not
attribute
all
exposure
from
dietary
of
arsenic
to
the
organic
arsenic
herbicides.
It
is
clearly
stated
in
the
dietary
assessment,
which
reads,
"
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 
Since
arsenic
is
ubiquitous
in
the
environment
and
was
quantified
as
total
arsenic
in
the
best
available
data,
it
was
Page
10
of
16
not
possible
to
determine
where
the
arsenic
originated
from
(
i.
e.,
background
or
from
pesticidal
use)
or
to
determine
speciated
residue
values
for
use
in
a
national
dietary
exposure
assessment "

HED
agrees
that
its
dietary
assessment
overestimates
potential
dietary
risks
to
inorganic
arsenic
and
this
it
clearly
states
in
its
assessment,
and
that
a
better
way
to
assess
the
dietary
risk
from
exposure
to
inorganic
arsenic
would
be
to
account
for
the
speciation
of
arsenic.
However,
there
are
not
adequate
available
speciated
arsenic
data
for
use
in
a
national
dietary
assessment.
The
critical
example
of
the
published
market
basket
survey
by
Schoof
et
al.
is
not
acceptable
for
use
in
a
national
assessment.
One
significant
reason
is
that
only
four
samples
of
each
commodity
were
collected
during
October
1997
from
large
supermarkets
in
two
towns.
This
is
not
adequate
sampling
for
a
national
dietary
assessment.
Speciated
data
for
a
national
dietary
assessment
must
have
samples
that
are
representative
of
the
entire
country.
Though
the
known
sample
origins
came
from
fourteen
different
states,
many
samples
origins
were
unknown,
and
there
was
no
northeast
or
Florida
representation.
It
is
also
unclear
if
the
cotton
belt
was
represented
in
the
sample
selection.
HED
agrees
that
this
assessment
has
valuable
information;
however,
it
is
not
appropriate
for
use
in
a
national
quantitative
dietary
exposure
assessment.

OPP
clearly
acknowledges
in
the
risk
assessment,
as
the
data
demonstrate,
that
arsenic
"
has
multiple
potential
sources,
both
from
natural
background
and
from
various
anthropogenic
activities."
Despite
its
own
acknowledgement
of
this
fact,
EPA
discounts
the
natural
background
levels
as
well
as
all
other
potential
sources
of
arsenic
and
attributes
all
arsenic
in
the
diet
to
the
use
of
MMA
and
DMA.

There
is
no
rational
basis
for
the
attribution
of
all
arsenic
in
the
diet
to
MMA
and
DMA.
This
assumption
is
inconsistent
with
available
data,
which
show
that
the
majority
of
the
arseniccontaining
agricultural
products
surveyed
in
FDA's
TDS
are
grown
in
states
that
do
not
use
the
methylated
arsenic
herbicides.
MSMA/
DSMA
agricultural
use
is
largely
restricted
to
the
"
cotton
belt"
and
includes
the
states
of
Georgia,
Mississippi,
Arkansas,
Louisiana,
Alabama,
Tennessee,
South
Carolina,
and
North
Carolina.
Lesser
amounts
are
used
in
California,
Arizona,
Texas,
North
Carolina,
and
New
Mexico.
Cacodylic
acid
is
currently
not
used
agriculturally
anywhere
in
the
U.
S.
The
cotton­
growing
states
do
not
overlap
with
the
states
that
produce
the
majority
of
corn,
soybean,
and
wheat.
For
example,
over
80%
of
all
corn
and
80%
of
flour
wheat
is
grown
in
states
that
do
not
use
MSMA.
Using
geographical
information
system
(
GIS)
data
analysis,
Waterborne
Environmental,
Inc.
was
able
to
show
that
no
more
than
14%
of
the
dietary
grain
(
including
wheat
and
rice)
are
estimated
to
be
rotated
with
corn,
and
that
turf
have
negligible
contribution
to
arsenic
residue
in
food
crops
(
Attachment
4).
Similarly,
a
large
portion
of
cattle
production
occurs
in
states
that
do
not
use,
or
have
limited
use,
of
methylated
arsenic
herbicides.
Even
more
striking,
saltwater
fish,
which
the
data
show
are
by
far
the
largest
source
of
arsenic
in
the
diet,
contains
large
concentrations
of
arsenic
in
the
form
of
compounds
that
are
not
related
to
the
organic
arsenic
herbicides,
and
would
not
be
expected
to
have
any
arsenic
from
methylated
herbicide
use.
Methylated
herbicide
use
could
not
plausibly
accumulate
in
saltwater
fish
in
the
quantities
measured
by
the
TDS.
Page
11
of
16
Using
total
arsenic
in
food
as
a
surrogate
for
inorganic
arsenic
leads
to
a
vast
overestimation
in
the
exposure
to
dietary
inorganic
arsenic.
The
significant
difference
in
result
that
occurs
when
the
relevant
data
are
considered
demonstrates
that
the
risk
assessment
would
not
be
scientifically
defensible
in
its
current
state.
EPA
must
eliminate
from
its
dietary
analysis
those
food
items
where
detected
arsenic
residues
cannot
plausibly
be
linked
to
the
application
and
use
of
the
methylated
arsenic
herbicides.
By
way
of
example
of
the
dramatic
impact
correcting
this
assumption
would
make,
by
eliminating
saltwater
fish
in
as
much
as
no
applications
of
methylated
arsenic
herbicides
are
likely
to
be
ingested
by
saltwater
fish,
estimates
of
arsenic
intake
will
decrease
by
45%
when
using
CSFII
intake
data,
and
by
up
to
60%
when
using
EPA's
data.

HED
Answer:
Again,
the
risk
assessment
clearly
states
that
HED
does
not
assume
that
all
arsenic
residues
or
exposure
are
from
the
organic
arsenic
herbicides.
The
dietary
assessment
states,
"
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 
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
pesticidal
use)
or
to
determine
speciated
residue
values
for
use
in
a
national
dietary
exposure
assessment "

It
is
important
to
note
that
for
residues
in/
on
cottonseed,
field
trial
data
were
used.
Cottonseed
is
the
only
commodity
where
HED
assumes
that
all
the
arsenic
dietary
exposure
is
coming
from
the
organic
arsenic
herbicide
uses.
For
all
additional
commodities,
HED
does
not
assume
that
all
arsenic
residues
are
coming
from
the
organic
arsenic
herbicide
uses
and
states
that
these
residues
are
also
from
background
sources.
However,
"
According
to
the
Food
Quality
Protection
Act
of
1996,
HED
must
consider
the
dietary
exposure
coming
from
all
sources
of
organic
arsenic.
All
sources
of
organic
arsenic
include
background
levels
of
organic
arsenic
that
are
in
food
commodities
and
drinking
water
that
are
not
necessarily
resulting
from
the
pesticidal
uses."

In
its
dietary
exposure
assessment,
OPP
uses
one­
half
the
limit
of
detection
(
LOD)
for
food
samples
with
non­
detected
arsenic
residues.
In
doing
so,
OPP
has
failed
to
follow
EPA's
own
guidance
on
the
evaluation
of
non­
detects
in
pesticide
risk
assessments.
Guidance
provides
that
the
use
of
½
LOD
is
appropriate
when
the
number
of
non­
detects
is
less
than
10­
15%.
However,
"[
w]
hen
the
number
of
non­
detects
increases
to
greater
than
10­
15%
(
but
is
still
less
than
50%),"
a
sensitivity
analysis
should
be
performed
to
verify
"
that
the
relevant
risk
and
exposure
estimates
are
not
significantly
affected."
and,
"
when
data
sets
consist
of
>
50%
non­
detects,
the
handling
of
[
those
non­
detects]
should
be
considered
on
a
case­
by­
case
basis
and
no
general
rule
of
thumb
is
possible."

The
number
of
non­
detects
greatly
exceeds
the
level
for
which
use
of
a
½
LOD
value
is
warranted
under
EPA's
guidance.
Consistent
with
this
guidance,
EPA
should
perform
a
Page
12
of
16
sensitivity
analysis.
Such
an
analysis
will
demonstrate
that
the
estimation
of
total
arsenic
intake
is
greatly
distorted
by
use
of
the
½
LOD
value,
as
discussed
in
more
detail
in
Attachments
1
and
2
to
this
letter.

HED
Answer:
HED
has
followed
guidance
concerning
the
use
of
½
LOD
as
a
default
value
for
commodities
which
have
been
treated
but
for
which
no
detectable
residues
are
measured.
It
is
not
appropriate
to
assume
that
the
non­
detectable
residues
of
arsenic
are
true
zeros,
since
residues
may
still
be
present
below
the
LOD.
The
guidance
states,
"
In
general,
the
Office
of
Pesticide
Programs
recommends
use
of
a
default
value
of
½
the
Limit
of
Detection
(
LOD)
or
½
the
Limit
of
Quantitation
(
LOQ)
for
commodities
which
have
been
treated
but
for
which
no
detectable
residues
are
measured.
This
paper
also
describes
OPP's
policy
of
performing
a
"
sensitivity
analysis"
to
determine
the
impact
of
using
different
assumptions
(
e.
g.,
assuming
NDs
=
full
LOD
or
full
LOQ
vs
NDs
=
zero),
on
the
OPP's
risk
assessment
for
the
pesticide
under
evaluation."
Sensitivity
analyses
are
typically
performed
only
when
there
are
risks
of
concern
that
may
influence
the
risk
decision.
Since
there
are
no
risks
of
concern
for
MMA
or
DMA,
additional
sensitivity
analyses
are
not
required
at
this
time.

The
MAA
Research
Task
Force
states
that
EPA
must
consider
valid
data
showing
that
MMA
and
DMA
make
up
only
a
small
fraction
of
total
dietary
arsenic.
EPA's
use
of
total
arsenic
as
a
surrogate
for
MMA
and
DMA
is
erroneous.
Valid,
existing
data
demonstrate
that
MMA
and
DMA
comprise
a
small
fraction
of
total
dietary
arsenic,
and
the
risk
assessment
must
account
for
those
data.

To
ensure
a
scientifically
valid
risk
assessment,
EPA
must
correct
its
error
and
make
use
of
available
MMA
and
DMA
urinary
concentrations
in
the
general
population
to
assess
dietary
exposures
to
these
organic
arsenicals.
Use
of
those
concentration
levels
would
mean
exposure
for
the
general
population
would
be
0.36%
of
the
cPAD
for
MMA
and
3.2%
of
the
cPAD
for
DMA
(
see
Attachment
10).

HED
Answer:
HED
has
considered
data
that
demonstrates
that
MMA
and
DMA
make
up
a
fraction,
in
some
cases,
of
total
dietary
arsenic
and
clearly
states
in
the
dietary
assessment,
"
Such
anticipated
residue
estimates
may
overestimate
the
dietary
exposure
and
risk
from
the
combined
agricultural
herbicidal
use
of
cacodylic
acid,
DSMA,
and
MSMA
during
a
single
season
of
use."

The
available
MMA
and
DMA
urinary
concentration
data
are
not
appropriate
for
a
national
arsenic
dietary
exposure
assessment.
"
According
to
the
Food
Quality
Protection
Act
of
1996,
HED
must
consider
the
dietary
exposure
coming
from
all
sources
of
organic
arsenic.
All
sources
of
organic
arsenic
include
background
levels
of
organic
arsenic
that
are
in
food
commodities
and
drinking
water
that
are
not
necessarily
resulting
from
the
pesticidal
uses."
Since
HED
must
consider
exposure
coming
from
all
sources,
it
is
inappropriate
to
include
individuals
who
"
refrain"
from
eating
fish,
where
a
majority
of
the
arsenic
exposure
is
coming
from,
if
it
is
part
of
their
usual
diet.
Also,
metabolism
data
demonstrates
that
arsenic
is
methylated
as
part
of
arsenic
Page
13
of
16
metabolism;
therefore,
using
MMA
and
DMA
concentrations
in
urine
does
not
determine
which
species
of
arsenic
the
person
was
actually
exposed.
It
is
important
to
note
that
the
HED
assessment
demonstrates
that
when
assuming
all
arsenic
residues
are
organic,
there
are
no
risks
of
concern;
therefore,
further
refinement
of
this
assessment
is
not
necessary
at
this
time.

The
Wood
Preservative
Science
Council
(
WPSC)
states
that
EPA
clearly
states
that
it
has
used
assumptions
"
that
are
not
standard"
in
its
dietary
exposure
analysis
for
the
organic
arsenic
herbicides
but
has
not
adequately
documented
those
assumptions
nor
publicly
vetted
its
assumptions
or
approaches,
which
include
assessment
of
background
arsenic
levels
and
assumptions
regarding
conversion
of
organic
to
inorganic
arsenic.
The
WPSC
believes
these
assumptions
and
approaches
are
inconsistent
with
Agency
policy.
Until
the
assumptions
and
approaches
are
fully
documented
and
subjected
to
appropriate
peer
review
and
public
comment,
and
then
further
reviewed
in
relation
to
appropriate
regulations
and
policy
positions,
the
WPSC
believes
that
no
contribution
from
background
levels
should
be
included
within
the
pesticide
risk
assessment
process
or
be
taken
into
account
in
decision
making.

In
fact,
the
Agency
typically
has
specifically
excluded
exposure
or
risk
from
background
of
such
naturally
occurring
compounds
as
part
of
its
decision
on
a
pesticidal
use,
even
for
compounds
which
are
considered
to
be
carcinogenic
and/
or
have
other
toxicological
effects
of
concern.
Further,
the
Agency
has
determined
that
where
compounds
are
naturally
occurring,
ubiquitous
in
the
environment,
incorporated
into
natural
plant
or
soil
constituents,
and
the
"
added"
amount
from
the
use
of
a
pesticide
indistinguishable
from
background
levels,
that
there
is
no
need
to
regulate
such
uses
as
food
uses.
Thus,
the
approach
presented
for
dietary
risk
assessment
of
organic
arsenical
herbicides
is
in
direct
opposition
to
established
precedent
and
documented
policy.

HED
Answer:
HED
does
state
that
it
has
used
assumptions
"
that
are
not
standard"
in
the
dietary
exposure
analyses
for
the
organic
arsenic
herbicides.
The
assumptions
are
documented
in
the
appendices
and
an
appropriate
peer
review
has
been
conducted.
HED's
Dietary
Exposure
Science
Advisory
Council
was
consulted
on
the
assumptions
and
approaches
and
reviewed
the
assessment,
and
a
public
comment
period
has
been
completed.

HED
understands
that
arsenic
exposure
comes
from
the
organic
arsenic
herbicide
uses
as
well
as
other
sources
and
that
the
herbicidal
uses
of
the
organic
arsenicals
contribute
to
arsenic
levels
in
the
soil
with
inter­
conversion
between
species.
According
to
the
Food
Quality
Protection
Act
of
1996,
HED
must
consider
the
dietary
exposure
coming
from
all
sources
of
organic
arsenic.
All
sources
of
organic
arsenic
include
background
levels
of
organic
arsenic
that
are
in
food
commodities
and
drinking
water
that
are
not
necessarily
resulting
from
the
pesticidal
uses.
Page
14
of
16
IV.
Occupational
and
Residential
Exposures
The
MAA
Research
Task
Force
states
that
OPP
errs
in
comparing
estimated
environmental
arsenic
levels
to
Soil
Screening
Levels
(
SSLs),
which
are
total
arsenic
levels
(
i.
e.,
levels
that
do
not
distinguish
between
organic
and
inorganic
arsenic
compounds).
SSLs
are
not
relevant
to
an
assessment
of
organic
arsenic
products.
SSLs
were
developed
by
another
EPA
office
under
the
Comprehensive
Environmental
Response,
Compensation,
and
Liability
Act,
an
unrelated
statutory
authority,
before
analytical
methods
could
distinguish
between
the
various
forms
of
arsenic.

HED
Answer:
HED
believes
that
the
EPA's
Office
of
Solid
Waste
and
Emergency
Response's
(
OSWER)
SSLs
are
relevant
to
an
assessment
of
organic
arsenic
products
because
HED
believes
that
the
application
of
organic
arsenic
herbicides
will
have
some
impact
on
total
arsenic
soil
levels
(
including
organic
and
inorganic
forms
of
arsenic).
OPP
believes
it
must
coordinate
with
other
offices
within
the
Agency
to
better
understand
and
anticipate
the
results
that
OPP's
actions
under
FIFRA
may
have
on
the
progress
of
other
offices.

HED
believes
that
characterization
of
the
SSL
discussion
in
the
risk
assessment
clearly
states
that
SSLs
are
not
national
clean­
up
standards
and
SSLs
alone
do
not
define
"
unacceptable"
levels
of
contaminants
in
soil.
HED
would
agree
that
the
estimation
of
arsenic
soil
levels
in
comparison
to
the
SSL
target
level
of
0.4
ppm
in
HED's
risk
assessment
is
conservative
in
nature.
However,
HED
clearly
states
this
in
the
risk
assessment
and
therefore
believes
that
this
discussion
should
remain.

The
MAA
Research
Task
Force
states
that
EPA
fails
to
consider
adequately
data
on
actual
practices
when
it
assumes
in
all
instances
that
there
is
100%
coverage
of
the
lawn.
The
major
use
for
DMA
in
a
residential
setting
is
as
a
lawn
edger,
not
for
applications
to
100%
of
lawns.
Application
to
100%
of
the
lawn
area
is
done
only
for
lawn
renovation.
For
lawn
edging,
the
100%
figure
is
grossly
excessive
and
unrealistic.
The
Master
Label
for
re­
registration
of
cacodylic
acid,
which
is
based
on
actual
product
use,
specifies
a
maximum
of
four
lawn
edging
applications
per
year,
while
the
Master
Labels
for
MSMA
and
DSMA
limit
lawn
applications
to
"
one
broadcast
application
per
year
with
all
other
applications
being
spot
treatments."
Lawn
edging
by
definition
involves
treatment
only
on
the
edges
of
a
lawn,
while
spot
treatments
are
for
spots,
not
the
entire
lawn.
As
the
edges
are
estimated
to
be
no
more
than
10%
of
the
total
lawn
area,
EPA
therefore
should
factor
in
a
maximum
coverage
of
10%
rather
than
100%.
This
10­
fold
reduction
leads
to
a
corresponding
10­
fold
reduction
in
risk.

HED
Answer:
HED
understands
that
DMA
is
registered
for
broadcast
and
edging
treatments,
however,
residential
postapplication
exposures
do
not
take
into
account
the
coverage
area
of
an
application.
It
is
assumed
that
an
individual
could
be
exposed
specifically
to
the
treated
lawn
edge.
This
is
especially
true
for
the
toddler
population
which
shows
risks
of
concern
for
hand
to
mouth
and
object
to
mouth
exposures
for
DMA.
Page
15
of
16
The
MAA
Research
Task
Force
and
the
Scott
Company
LLC
state
that
EPA
should
not
use
default
assumptions
of
20
toddler
hand­
to­
mouth
events
per
hour
with
20
cm2
of
the
hand
contacting
the
mouth
in
the
risk
assessment.
Studies
submitted
to
EPA
that
were
conducted
by
the
Outdoor
Residential
Exposure
Task
Force
(
ORETF),
whose
members
include
the
members
of
the
Task
Force,
put
the
frequency
of
toddler
hand­
to­
mouth
contact
at
9.2
events
per
hour
and
the
surface
area
of
the
hand
mouthed
at
7.7
cm.
These
newly
produced,
valid,
relevant
data
cannot
be
disregarded
by
EPA
in
favor
of
default
assumptions
based
on
only
an
older
subset
of
the
currently
available
data.

HED
Answer:
The
HED
Residential
Standard
Operating
Procedures
states
that
it
is
HED
policy
to
use
the
assumptions
of
20
toddler
hand­
to­
mouth
events
per
hour
and
20
cm2
of
the
hand
contacting
the
mouth
when
calculating
hand
to
mouth
exposures.
These
values
were
selected
on
the
basis
of
recommendations
given
by
the
February
1999
Scientific
Advisory
Panel.
At
the
present
time,
HED
has
no
plans
to
alter
its
policy
and
utilize
the
data
presented
in
the
two
ORETF
studies
mentioned
above.

For
more
information
on
the
HED
Residential
Standard
Operating
Procedures
see
Standard
Operating
Procedures
(
SOPs)
for
Residential
Exposure
Assessments.
Contract
No.
68­
W6­
0030.
Work
Assignment
No.
3385.102.
Prepared
by
The
Residential
Exposure
Assessment
Work
Group.
Office
of
Pesticide
Programs,
Health
Effects
Division
and
Versar,
Inc.
December
1997.
[
Revised
Feb.
22,
2001;
HED
Science
Advisory
Council
for
Exposure
Policy
#
12].

The
MAA
Research
Task
Force
states
the
default
assumptions
of
20%
and
5%
being
transferable
to
a
worker
and
resident,
respectively
should
not
be
used
in
the
risk
assessment.
Instead,
the
Task
Force,
believes
a
Turf
Transferable
Residue
(
TTR)
study
(
MRID
449589­
01
)
that
shows
the
TTR
for
MSMA
should
be
used
in
place
of
the
assumptions.

HED
Answer:
For
occupational
postapplication
exposure,
HED
utilized
the
MSMA
TTR
data
to
assess
postapplication
risks
to
CAMA,
DSMA,
and
MSMA.
The
data
were
not
used
to
assess
postapplication
risks
to
DMA.
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.
As
stated
in
the
Phase
3
HED
risk
assessment,
HED
still
agrees
with
this
decision.
As
a
result,
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.

For
residential
postapplication
exposure,
the
measured
TTR
levels
quantified
in
the
MSMA
TTR
study
were
not
used
to
complete
the
short­
term
dermal
exposure
calculations
as
the
0­
day
Page
16
of
16
transferability
was
<
1
percent
of
the
application
rate.
It
is
HED
policy
to
not
use
TTR
studies
for
residential
postapplication
risk
assessment
purposes
when
the
transferability
is
less
than
1
percent
because
the
transfer
coefficients
used
by
the
Agency
for
defining
exposures
are
based
on
Jazzercize
studies
in
which
TTR
values
were
measured
by
techniques
where
transferability
is
generally
in
the
1
to
5
percent
range.
In
these
cases,
HED
utilizes
the
standard
assumptions
taken
from
HED's
Residential
Standard
Operating
Procedures.

A
private
citizen
stated
that
the
re­
registration
process
for
the
organic
arsenic
herbicides
should
proceed
with
the
elimination
of
any
approved
label
uses
for
these
products
on
athletic
fields,
recreation
areas,
and
parks
due
to
the
potential
for
inhalation
exposure
to
inorganic
arsenic
sorbed
to
fine
particulates
during
active
recreational
use
of
these
areas
and
in
fact
the
labels
should
include
a
specific
warning
against
such
usage.

HED
Answer:
HED
does
not
believe
that
inhalation
exposure
to
inorganic
arsenic
sorbed
to
fine
particles
is
a
route
of
exposure
that
would
be
considered
a
driver
in
the
organic
herbicides
risk
assessment.
HED
believes
that
dermal
and
incidental
oral
risks
would
be
many
times
greater
than
the
risks
coming
from
inhalation
of
"
arsenic
soil
dust"
and
its
contribution
to
the
risk
would
be
expected
to
be
negligible.

The
Florida
Department
of
Agriculture
and
Consumer
Services
(
FDACS)
states
that
there
is
no
evaluation
of
the
acute
or
chronic
risks
associated
with
exposure
at
sites
that
had
received
multiple
applications
over
a
period
of
years
(
e.
g.,
parks,
schools,
athletic
fields).
EPA
concluded
that
the
residential
post­
application
risks
were
not
unacceptable,
but
only
evaluated
the
impact
of
a
single
year's
application.
In
addition,
the
EPA
concluded
that
the
Soil
Screening
Level
(
0
.4
ppm)
would
be
exceeded
with
a
single
organic
arsenical
herbicide
application,
and
stated
"
.
.
.
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
."
Therefore,
FDACS
concludes
that
this
exposure
scenario
is
a
viable
one
for
both
acute
and
chronic
time­
frames
and
should
be
evaluated.

HED
Answer:
HED
agrees
with
FDACS
that
this
exposure
scenario
exists
and
HED
believes
that
it
has
addressed
these
scenarios
in
a
qualitative
manner.
HED
does
not
believe
that
it
would
be
valid
to
combine
multiple
conservative
estimates
(
maximum
application
rates,
maximum
number
of
applications
per
year,
soil
build­
up,
bioavailability,
etc.)
and
produce
a
quantitative
assessment
for
this
type
of
scenario.
Such
an
assessment
would
not
be
very
scientifically
defensible
and
it
would
be
extremely
limited
for
regulatory
use.