Document ID: EPA-HQ-OPP-2005-0163-0039
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-05-17T04:00Z

Page
1
of
51
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
May
12,
2006
MEMORANDUM
SUBJECT:
Aldicarb
(
List
A
Case
0140,
Chemical
ID
No.
098301).
HED
Revised
Preliminary
Human
Health
Risk
Assessment
for
the
Reregistration
Eligibility
Decision
Document
(
RED).
DP
Barcode
No.
D327738.

FROM:
Felecia
Fort,
Chemist
Reregistration
Branch
1
Health
Effects
Division
(
7509C)

THRU:
Michael
Metzger,
Branch
Chief
Reregistration
Branch
1
Health
Effects
Division
(
7509C)

TO:
Sherrie
Kinard,
Chemical
Review
Manager
Special
Review
Branch
Special
Review
and
Reregistration
Division
(
7508W)

Attached
is
a
revised
human
health
risk
assessment
for
aldicarb
prepared
by
Reregistration
Branch
1
(
RRB1)
of
the
Health
Effects
Division.
This
document
has
been
revised
to
incorporate
comments
received
by
the
registrant,
Bayer
CropScience
during
the
Phase
1
"
error
only"
comment
period.
A
response
to
comments
document
was
also
prepared
which
summarizes
and
illustrates
specifically
how
the
comments
were
addressed
for
the
risk
assessment.
This
document
is
entitled
"
Aldicarb.
List
A
Reregistration
Case
No.
0140/
Chemical
ID
No.
098301.
HED's
Response
to
Bayer
CropScience
"
Error
Only"
Comments.
DP
Barcode
No.
D320377."

The
aldicarb
risk
assessment
team
is
comprised
of
Felecia
Fort
(
risk
assessment,
and
dietary
exposure
assessment);
Christina
Swartz
(
residue
chemistry
chapter,
previous
risk
assessor);
Linda
Taylor
(
hazard
assessment),
Jeff
Dawson
(
occupational
risk
assessment),
and
Jonathan
Angier,
EFED
(
drinking
water
estimates).
The
risk
assessment
and
supporting
documentation
have
been
reviewed
by
the
Risk
Assessment
Review
Committee
(
RARC).

The
intentional
dosing
human
toxicity
study
used
in
this
risk
assessment
has
been
reviewed
by
EPA's
Human
Studies
Review
Board,
as
required
by
EPA's
Human
Subjects
Protections
rule,.
The
Human
Page
2
of
51
Subjects
Protections
rule
40
CFR
part
26
(
effective
April
7,
2006)
requires
that
the
Inveresk
study
 
an
intentional
dosing,
human
toxicity
study
on
which
EPA
is
relying
in
this
risk
assessment
 
be
reviewed
by
the
Human
Studies
Review
Board
(
HSRB).
The
Agency
presented
the
Inveresk
study
to
the
HSRB
at
a
meeting
on
April
2
 
4,
2006.
The
HSRB
discussed
the
study
extensively
during
this
meeting
and
is
in
the
process
of
preparing
a
written
report
summarizing
its
discussions.
The
Agency
believes
that
the
oral
comments
of
the
HSRB
provided
a
sufficient
indication
of
the
conclusions
likely
to
appear
in
the
HSRB's
final
report
that
EPA
could
confidently
move
ahead.
These
preliminary
recommendations
from
HSRB
are
incorporated
into
this
document.

Note
to
Risk
Manager:
Updated
pesticide
residue
monitoring
data
from
the
USDA
Pesticide
Data
Program
(
PDP)
have
not
been
incorporated
into
the
preliminary
dietary
exposure
assessment.
However,
the
monitoring
data
support
the
results
of
the
current
assessment,
and
these
data
are
not
expected
to
result
in
any
significant
changes
in
estimated
dietary
exposure.
It
should
also
be
noted
that
this
assessment
supercedes
the
previous
occupational
and
residential
exposure
(
ORE)
assessment
(
D311821;
January
11,
2005;
Author:
Jeff
Dawson)
and
Toxicology
RED
chapter
(
D266321;
August
20,
2002;
Author:
Linda
Taylor,
Ph.
D).
These
chapters
were
not
revised
and
reissued;
instead,
certain
relevant
modifications
were
included
in
this
document.
Page
3
of
51
HUMAN
HEALTH
RISK
ASSESSMENT
Aldicarb
U.
S.
Environmental
Protection
Agency
Office
of
Pesticide
Programs
Health
Effects
Division
(
7509C)
Felecia
Fort,
Chemist/
Risk
Assessor
Date:
May
12,
2006
Page
4
of
51
HUMAN
HEALTH
RISK
ASSESSMENT
Aldicarb
Risk
Assessment
Team:

Risk
Assessor:
Felecia
A.
Fort
Residue
Chemistry/
Dietary
Assessment
Felecia
Fort
Christina
Swartz
Occupational
and
Residential
Exposure:
Jeffrey
Dawson
Toxicology:
Linda
Taylor,
Ph.
D
Drinking
Water
Estimates:
Jonathan
Angier,
Ph.
D
Page
5
of
51
TABLE
OF
CONTENTS
1.0
EXECUTIVE
SUMMARY........................................................................................................
1
2.0
PHYSICAL/
CHEMICAL
PROPERTIES..................................................................................
12
3.0
HAZARD
ASSESSMENT........................................................................................................
12
3.1
Hazard
Profile
...............................................................................................................
12
3.2
FQPA
Considerations....................................................................................................
18
3.3
Dose
Response
Assessment
...........................................................................................
20
3.4
Endocrine
Disruption
....................................................................................................
25
4.0
EXPOSURE
ASSESSMENT
AND
CHARACTERIZATION...................................................
25
4.1
Summary
of
Registered
Uses.........................................................................................
25
4.2
Dietary
Exposure/
Risk
Pathway
....................................................................................
26
4.2.1
Residue
Profile
...............................................................................................
26
4.2.2
Dietary
Exposure
............................................................................................
29
4.2.2.1
Acute
Dietary
Exposure....................................................................
30
4.2.2.2
Chronic
Dietary................................................................................
32
4.3
Water
Exposure/
Risk
Pathway
......................................................................................
34
4.3.1
Environmental
Fate
Properties
........................................................................
34
4.3.2
Estimated
Environmental
Concentrations
(
EECs)/
Monitoring
Data.................
35
4.4
Residential
Exposure/
Risk
Pathway...............................................................................
38
5.0
AGGREGATE
RISK
ASSESSMENTS
AND
RISK
CHARACTERIZATIONS
.......................
39
5.1
Acute
Aggregate
Risk
Assessment
................................................................................
40
5.1
Chronic
Aggregate
Risk
Assessment
.............................................................................
43
6.0
CUMULATIVE
RISK..............................................................................................................
44
7.0
OCCUPATIONAL
EXPOSURE
..............................................................................................
45
7.1
Handler
.........................................................................................................................
48
7.2
Postapplication..............................................................................................................
51
8.0
DATA
NEEDS/
LABEL
REQUIREMENTS
.............................................................................
53
8.1
Toxicology....................................................................................................................
53
8.2
Residue
Chemistry
........................................................................................................
53
9.0
SUPPORTING
DOCUMENTATION.......................................................................................
53
Page
6
of
51
1.0
EXECUTIVE
SUMMARY
The
Health
Effects
Division
(
HED)
of
EPA's
Office
of
Pesticide
Programs
has
evaluated
the
toxicity
and
exposure
databases
for
the
pesticide
active
ingredient
aldicarb,
and
has
conducted
a
human
health
risk
assessment
to
support
the
reregistration
of
products
containing
aldicarb.
This
risk
assessment
addresses
risks
to
aldicarb
alone,
and
does
not
consider
cumulative
effects
of
other
carbamate
pesticides.

Use
and
Usage
Information
Aldicarb
is
registered
for
use
as
a
systemic
insecticide,
acaricide
and
nematicide
on
agricultural
crops
including
citrus,
cotton,
dry
beans,
peanuts,
pecans,
potatoes,
sorghum,
soybeans,
sugar
beets,
sugarcane,
sweet
potatoes,
and
seed
alfalfa
(
CA).
In
addition,
aldicarb
may
be
applied
to
field
grown
ornamentals
(
CA)
and
tobacco,
and
on
coffee
grown
in
Puerto
Rico.
Pests
controlled
by
aldicarb
include
leaf
phylloxera;
bud
moth;
citrus
nematode
(
suppression);
aphids;
mites;
white
flies;
thrips;
fleahoppers,
leafminers;
leafhoppers;
overwintering
boll
weevil;
lygus;
nematodes
(
suppression);
cotton
leaf
perforator;
seedcorn
maggot;
Mexican
bean
beetle;
flea
beetles;
Colorado
potato
beetle;
greenbug;
chinch
bug;
three
cornered
alfalfa
hopper
(
suppression);
and
sugar
beet
root
maggot.

Aldicarb
is
a
restricted
use
pesticide,
and
may
only
be
applied
in
occupational
settings
by
certified
applicators.
There
are
no
aldicarb
products
intended
for
sale
to
homeowners
or
for
use
in
residential
settings.
Aldicarb
is
formulated
and
marketed
solely
as
a
granular
pesticide
under
the
trade
name
Temik
®
.
The
granulars
(
5,
10
and
15%)
consist
of
aldicarb
adhered
to
a
corn
cob
grit
or
gypsum
substrate,
which
are
formulated
to
produce
less
dust
than
typical
clay
substrates
used
for
granular
pesticides.
The
gypsum
granular
is
available
in
closed
loading
systems.
Aldicarb
is
applied
early
in
the
growing
season,
either
pre­
plant,
at­
planting,
or
early
post­
emergent,
using
ground
application
equipment.
Positive
displacement
application
equipment
and
immediate
soil
incorporation
are
required.

Regulatory
Background
Aldicarb
is
currently
under
Special
Review
because
of
concerns
regarding
ground
water
contamination.
Position
Documents
(
PD's)
1
and
2/
3
were
published
on
7/
11/
84
(
49
FR
28320)
and
6/
29/
88
(
53
FR
24630),
respectively.
A
Special
Review
Data
Call­
In­
Notice
(
DCI)
was
issued
6/
3/
89
requiring
the
registrant
to
submit
additional
ground
water
data.
In
addition,
because
a
National
Food
Survey
identified
discrepancies
between
anticipated
residues
in
foods
and
actual
residues
from
food
survey
samples,
the
Special
Review
required
a
variety
of
studies
related
to
use
on
potatoes
and
citrus
crops.
In
1990,
the
sale
and
use
of
aldicarb
on
potatoes
were
voluntarily
suspended
due
to
detection
of
tolerance­
exceeding
aldicarb
residues
on
individual
potatoes.
Additional
studies
were
conducted
to
alleviate
concerns
for
dietary
risk
due
to
high
residues
in
potatoes,
and
the
use
was
reinstated
in
the
states
of
FL,
ID,
WA
and
OR
(
EPA
Desk
Statement,
9/
22/
95).
Aldicarb
remains
in
EPA's
Special
Review
process
because
of
continued
concerns
about
ground
water
contamination.
A
PD4
is
to
be
issued
in
conjunction
with
a
reregistration
eligibility
decision.
Registrations
of
aldicarb
currently
reside
with
Bayer
Corporation.
Page
7
of
51
Hazard
Profile
and
Food
Quality
Protection
Act
(
FQPA)
Decision
Aldicarb
is
a
N­
methyl
carbamate
pesticide
that
exerts
its
pesticidal
activity
and
elicits
adverse
toxic
effects
by
inhibition
of
cholinesterase
activity
[
ChEI].
Overall,
the
studies
supporting
the
toxicity
database
for
aldicarb
are
considered
adequate,
and
there
is
confidence
in
the
hazard
and
dose
response
assessments.
Acutely,
aldicarb
is
highly
toxic
via
the
oral,
dermal,
and
inhalation
routes
of
exposure
(
Toxicity
Category
1).
It
is
not
a
dermal
sensitizer;
dermal
and
eye
irritation
studies
were
waived
due
to
severe
effects
(
death)
following
corneal
and
dermal
dosing.

The
toxicity
database
for
aldicarb
is
adequate,
including
acceptable
studies
submitted
to
determine
toxic
effects
associated
with
acute,
subchronic
and
chronic
exposure
durations
by
the
oral
route;
acceptable
acute
and
subchronic
neurotoxicity
studies;
a
developmental
neurotoxicity
study
in
rats;
developmental
studies
(
rat
and
rabbit);
and
a
reproduction
study
(
rat).
Acceptable
dermal
and
inhalation
toxicity
and
dermal
penetration
studies
are
not
available.

Aldicarb
toxicity
studies
have
demonstrated
inhibition
of
cholinesterase
activity
in
whole
blood,
plasma,
red
blood
cells
(
RBC)
and
brain
of
rats,
mice,
and
dogs
following
acute,
subchronic,
and
chronic
exposures
and
in
plasma
and
RBC
in
humans
following
acute
exposure.
It
should
be
noted
that
aldicarb
induced
ChEI
has
been
shown
to
be
reversible
in
less
than
24
hours.
Both
the
acute
and
subchronic
rat
neurotoxicity
studies
show
a
variety
of
typical
clinical
signs
of
ChEI
after
oral
exposures
to
aldicarb,
including
decreased
motor
activity,
lacrimation,
tremors,
salivation,
pinpoint
pupils,
and
decreased
grip
strength.

In
guideline
developmental
or
reproduction
studies
including
a
rat
developmental
neurotoxicity
study
submitted
by
the
registrant,
there
was
no
indication
of
qualitative
or
quantitative
susceptibility
of
offspring.
Maternal
toxicity
occurred
at
doses
where
no
offspring
toxicity
was
observed;
i.
e.,
the
no
observed
adverse
effects
level
(
NOAEL)
for
maternal
toxicity
was
lower
than
the
offspring
NOAEL.
A
published
non­
guideline
oral
acute
neurotoxicity
study
conducted
by
EPA/
ORD
(
Moser)
reported
evidence
for
increased
sensitivity
of
young
rats
based
on
brain
ChEI
measurements.
Decreased
motor
activity
was
observed
only
in
the
adult
animals,
and
clinical
signs
of
ChEI
occurred
more
frequently
and
recovery
was
prolonged
in
the
adult
than
in
the
young
animal.
The
magnitude
of
the
brain
ChEI
was
approximately
2­
fold
greater
in
the
young
rat
compared
to
the
adult
rat
at
similar
acute
doses.
Therefore,
a
FQPA
safety
factor
of
2X
is
retained.

In
an
acute
oral
study
conducted
in
human
volunteers,
aldicarb
treatment
of
both
males
and
females
resulted
in
statistically­
significant
inhibition
of
both
red
blood
cell
and
plasma
cholinesterase
at
two
common
dose
levels.
The
results
of
the
acute
oral
human
study
suggest
a
two­
fold
difference
between
animals
and
humans
with
respect
to
toxic
responses
following
acute
exposure
to
aldicarb.

The
metabolism
of
aldicarb
is
well
understood
in
animals
(
livestock
and
rats),
plants,
and
in
the
environment
(
soil
and
water).
In
rats,
with
oral
administration,
aldicarb
is
rapidly
absorbed,
widely
distributed,
and
rapidly
eliminated.
In
rats,
livestock,
plants,
and
in
the
environment,
aldicarb
is
rapidly
metabolized
to
aldicarb
sulfoxide,
with
a
smaller
amount
then
slowly
converted
to
aldicarb
sulfone.
These
three
moieties
(
aldicarb,
sulfoxide,
and
sulfone)
may
then
Page
8
of
51
be
further
metabolized
to
oximes
and
nitriles.
Both
the
sulfoxide
and
sulfone
are
also
potent
cholinesterase
inhibitors.
The
sulfone
is
less
toxic
following
an
acute
oral
exposure
than
either
the
parent
compound
or
the
sulfoxide,
which
show
comparable
acute
oral
toxicity.
Aldicarb
and
its
two
cholinesterase­
inhibiting
metabolites
are
the
residues
of
concern
for
risk
assessment
for
all
routes
of
exposure
and
for
tolerance
reassessment.

There
are
acceptable
genotoxicity
studies
for
all
three
required
categories
of
mutagenic
effects:
gene
mutations,
chromosomal
aberrations,
and
other
genotoxic
effects.
The
results
of
these
studies
are
all
negative.
Aldicarb
is
not
considered
a
mutagen,
and
it
is
classified
as
Category
E,
Evidence
of
Non­
Carcinogenicity
for
Humans,
based
on
the
lack
of
evidence
of
carcinogenicity
in
studies
in
rats
and
mice.

Consideration
of
all
available
toxicity
data
was
used
to
determine
the
toxicity
endpoints
and
reference
doses
appropriate
for
the
aldicarb
risk
assessment.
Criteria
utilized
in
determining
the
appropriate
toxicity
endpoints
and
reference
doses
included
the
quality
and
reliability
of
the
studies
and
the
presence
of
sound
dose­
response
data.
The
risk
assessment
team
examined
a
human
oral
study
as
part
of
its
deliberations.
It
was
concluded
that
the
human
study
can
be
relied
upon
in
this
risk
assessment
to
inform
the
interspecies
factor.
This
human
study
also
has
been
reviewed
by
the
Human
Studies
Review
Board
whose
decision
affirmed
the
team's
conclusion.
The
team
considered
the
subchronic
and
acute
neurotoxicity
studies
in
rats
to
be
the
most
suitable
for
risk
assessment
purposes.

Dose
Response
Assessment
Acute
RfD
In
order
to
evaluate
the
appropriate
point
of
departure
(
PoD)
for
ChEI,
the
Agency
considered
benchmark
dose
(
BMD)
estimates
developed
from
the
rat
acute
and
subchronic
neurotoxicity
studies
and
the
non­
guideline
neurotoxicity
study
(
Moser)
along
with
BMD
estimates
provided
in
the
preliminary
cumulative
risk
assessment
for
N­
methyl
carbamates
(
NMC;
presented
to
the
FIFRA
SAP
in
February
and
August,
2005;
USEPA,
2005).
In
the
current
analysis,
the
Agency
used
data
from
both
the
registrant's
dose­
response
studies
and
from
the
Agency's
comparative
study
(
adult
rat
data
only).
The
Agency
believes
that
use
of
data
from
multiple
studies
provides
a
more
robust
analysis
than
a
single
study.
The
results
of
the
combined
analysis
indicate
that
in
adult
rats,
RBC
ChE
inhibition
is
slightly
more
sensitive
than
brain
ChE
inhibition
(
ie,
BMDL10
0.02
mg/
kg
compared
to
0.03
mg/
kg;
respectively;
BMD10
0.03
mg/
kg
compared
to
0.05­
0.06
mg/
kg,
respectively).
Considering
this
and
given
that
dose­
related
changes
in
behavioral
endpoints
and
clinical
signs
have
been
observed
at
the
higher
doses
of
aldicarb,
at
this
time,
the
Agency
considers
the
RBC
ChE
inhibition
data
from
the
animal
studies
to
be
sufficiently
reliable
for
developing
a
point
of
departure
for
risk
assessment
purposes.

A
human
toxicity
study
was
also
considered.
The
measured
RBC
ChE
activity
from
the
human
study
is
adequate
for
estimation
of
BMD
and
BMDL
estimates.
The
RBC
ChE
data
from
the
aldicarb
human
study
were
utilized
in
the
model
in
the
same
manner
as
the
acute
rat
data
(
brain
and
RBC)
that
are
available
for
the
NMCs
of
the
cumulative
hazard
assessment
(
USEPA
2005).
The
ratio
of
RBC
BMDL10
rat
(
adult
rat;
both
sexes)
to
RBC
BMDL10
human
(
both
sexes)
is
2X.
The
human
RBC
data,
therefore,
were
utilized
by
the
Agency
to
inform
the
pesticidespecific
interspecies
extrapolation.
Note
that
EPA's
use
of
a
human
toxicity
study
in
the
Page
9
of
51
aldicarb
risk
assessment
is
in
accordance
with
the
Agency's
Final
Rule
promulgated
on
January
26,
2006,
related
to
Protections
for
Subjects
in
Human
Research,
which
is
codified
in
40
CFR
Part
26.

There
was
no
evidence
of
increased
sensitivity
in
developing
animals
in
any
of
the
guideline
studies
reviewed.
Aldicarb
did
not
result
in
developmental
toxicity
in
either
rats
or
rabbits
or
in
reproductive
effects
in
the
rat
multi­
generation
reproduction
study.
Additionally,
there
was
no
developmental
toxicity
in
the
developmental
neurotoxicity
study
in
rats.
However,
the
comparative
ChE
inhibition
study
[
Moser]
demonstrated
that
pups
were
more
sensitive
than
the
adults
with
respect
to
brain
ChEI.
Based
on
benchmark
dose
(
BMD)
estimates
calculated
from
these
data,
the
pups
are
2X
more
sensitive
than
the
adults
[
brain
BMD10s
ranged
from
0.014
to
0.020
in
juvenile
animals
and
0.024
to
0.031
in
adult
animals].
Therefore,
a
FQPA
safety
factor
of
2X
is
retained.

The
acute
reference
dose
(
aRfD)
for
dietary
exposure
assessment
was
derived
by
dividing
the
rat
RBC
BMDL10
as
the
point
of
departure
[
0.02
mg/
kg]
by
an
intraspecies
factor
of
10X
and
an
interspecies
factor
of
2X,
resulting
in
an
acute
RfD
of
0.001
mg/
kg.
Using
the
FQPA
SF
of
2X,
the
population
adjusted
dose
(
aPAD)
is
0.0005
mg/
kg.
For
additional
risk
characterization,
aPADs
using
the
rat
brain
and
human
RBC
BMDL10
were
determined.
The
aPAD
based
on
rat
brain
ChEI
is
0.00075
mg/
kg
and
the
aPAD
based
on
human
RBC
BMDL10
is
0.00065
mg/
kg/
day.
More
detailed
information
about
the
derivation
these
aPADs
can
be
found
in
the
Dose
Response
chapter
in
this
document.

Chronic
RfD
Aldicarb­
induced
inhibition
of
ChE
activity
is
rapidly
reversible
(
less
than
24
hours).
Therefore,
chronic
exposure
to
aldicarb
is
considered
to
be
a
series
of
acute
exposures,
and
a
separate
chronic
assessment
is
not
necessary.

There
are
no
residential
uses
of
aldicarb
so
a
residential
exposure
assessment
was
not
done.

Dermal
and
Inhalation
There
are
no
suitable
dermal
or
inhalation
toxicity
studies
for
aldicarb
risk
assessment
purposes.
Therefore,
the
Agency
selected
the
same
dose
and
endpoint
(
0.02
mg/
kg/
day,
based
on
RBC
ChEI)
for
short­
term
dermal
and
inhalation
risk
assessments.
The
BMDL10
value
of
0.02
mg/
kg/
day
in
the
rat
calculated
from
the
adult
RBC
ChEI
data
is
appropriate
for
assessing
dermal
and
inhalation
exposure
risks
(
all
durations)
for
occupational
workers
(
the
most
sensitive
effect
in
the
population
of
concern,
adults).
Only
short­
and
intermediate
term
(
i.
e.,
no
long
term
exposures)
dermal
and
inhalation
exposures
are
expected
to
occur
based
on
the
use
patterns
for
aldicarb.
The
target
margin
of
exposure
(
MOE)
is
20
(
i.
e.,
10X
for
intraspecies
variability
and
2x
for
interspecies
extrapolation).

A
default
100%
dermal
absorption
rate,
relative
to
oral
exposures,
is
applied
for
route­
to­
route
extrapolation.
A
default
100%
inhalation
absorption
rate,
relative
to
oral
exposures,
is
applied
for
route­
to­
route
extrapolation.
Page
10
of
51
The
submitted
dermal
toxicity
studies
are
considered
unacceptable,
and
there
is
no
dermal
penetration
study;
therefore,
dermal
exposure
assessments
have
been
conducted
assuming
default
dermal
absorption
factor
of
100%
relative
to
oral
dosing.
A
comparison
of
cholinesterase
data
from
unacceptable
dermal
toxicity
studies
to
cholinesterase
data
from
oral
studies
suggests
100%
dermal
absorption
is
conservative,
and
therefore
protective,
for
dermal
exposures.
An
inhalation
absorption
factor
of
100
%
relative
to
oral
exposures
was
applied
in
assessing
inhalation
exposure
and
risk
for
aldicarb.
In
accordance
with
Agency
policy,
the
FQPA
SF
does
not
apply
to
occupational
assessments.

Reversibility
of
Aldicarb­
Induced
Cholinesterase
Inhibition
The
registrant
proposed
refinements
to
the
acute
dietary
exposure
and
risk
assessment
based
on
the
recovery
of
cholinesterase
inhibition
resulting
from
exposure
to
aldicarb
at
low
doses.
The
underlying
assumption
for
this
approach
is
complete
recovery
of
cholinesterase
activity
to
predose
levels
within
8
hours
of
exposure,
and
that
full
recovery
of
behavioral
and
neurochemical
function
to
pre­
dose
levels
indicates
sensitivity
to
subsequent
exposures
to
aldicarb
has
returned
to
baseline.
The
registrant
argues
that
the
Agency
has
overestimated
risk
by
summing
aldicarb
exposure
from
all
food
consumed
over
a
24­
hour
period
and
treating
this
as
if
it
were
a
single
exposure
(
i.
e.,
the
Agency
has
not
accounted
for
the
possibility
that
there
could
be
time
between
eating
events,
and
thus
exposure
to
aldicarb,
where
some
recovery
or
complete
recovery
could
occur).

In
developing
its
approach
to
assessing
the
cumulative
exposure
and
risk
to
the
Nmethylcarbamates
the
Agency
examined
the
exposure
patterns
for
food
records
from
the
high
end
of
exposure
distribution.
A
case
study
was
presented
to
the
Scientific
Advisory
Panel
in
February,
2005.
The
results
of
the
analysis
indicated
that
daily
exposures
to
n­
methyl
carbamate
pesticides,
of
which
aldicarb
is
a
member
in
the
upper
extremes
of
the
distribution
(
99.8+
percentile)
for
exposures
from
food
mainly
involve
single
eating
events.
Specifically,
EPA
found
that
a
large
fraction
(~
70%)
of
daily
records
contributing
to
the
upper
tail
of
the
food
exposure
distribution
represent
single
eating
occasions.
Given
that
the
large
majority
of
daily,
high­
end
food
exposures
to
NMC
pesticides
appear
to
be
associated
with
food
intake
at
a
single
eating
event
during
the
day,
the
Agency
believes
that
it
is
unlikely
that
any
more
sophisticated,
temporal­
based
approach
which
better
accounts
for
temporal
separation
of
eating/
exposure
events
will
result
in
substantial
or
significant
changes
in
risk
estimates
associated
with
exposure
through
food.
Thus,
for
food
exposure,
when
discussing
the
most
highly
exposed
individuals,
the
issue
of
recovery
times
and
their
effect
on
those
high­
end
exposures
is
likely
to
be
of
limited
practical
significance.
The
specifics
associated
with
these
analyses
can
be
found
in
the
NMC
case
study
presented
to
the
SAP
in
February
2005
(
US
EPA,
2005).

Exposure
Assessment
The
use
pattern
for
aldicarb
is
expected
to
result
in
exposure
to
the
general
population
through
food
and
drinking
water.
There
is
a
potential
for
inhalation
exposure
from
aldicarb­
treated
tobacco,
but
there
are
no
residential
uses
or
agricultural
uses
that
would
result
in
residential
exposure
to
the
general
population.
Exposures
can
occur
for
occupational
handlers
loading
or
applying
aldicarb
granulars,
but
no
postapplication
exposure
is
expected
because
aldicarb
is
soilincorporated
at
planting.
Page
11
of
51
Aldicarb
Exposure
from
Food
The
residue
chemistry
database
is
essentially
complete,
including
acceptable
plant
and
animal
metabolism
studies,
analytical
methods,
field
residue
trials,
processing
studies
and
rotational
crop
studies.
The
data
are
adequate
for
both
tolerance
reassessment
and
dietary
exposure
assessment.
Aldicarb
residues
are
not
expected
in
livestock
commodities
such
as
meat,
milk
and
eggs,
and
residues
in
most
field
crops
are
low
or
nondetectable.
Higher
residues
(
primarily
of
aldicarb
metabolites
and
not
aldicarb
per
se)
have
historically
been
found
in
monitoring
of
citrus
and
potato
commodities,
including
individual
oranges
and
potatoes.

HED
conducted
a
highly
refined
acute
(
probabilistic)
dietary
exposure
assessments
using
the
Dietary
Exposure
Evaluation
Model
(
DEEM­
FCID
 
)
and
consumption
data
from
the
US
Department
of
Agriculture
(
USDA)
Continuing
Surveys
of
Food
Intake
by
Individuals
(
CSFII,
1994­
1996
and
1998.).
The
acute
dietary
exposure
assessment
incorporated
monitoring
and
market
basket
survey
data
from
the
USDA
Pesticide
Data
Program
(
PDP,
potatoes)
and
the
Carbamate
Task
Force
(
CTF,
oranges).
These
two
data
sets
were
used
to
assess
exposure
from
all
potato
and
sweet
potato
food
forms,
as
well
as
all
citrus
(
orange,
grapefruit,
lemon
and
lime)
food
forms.

The
PDP
and
CTF
data
were
considered
the
best
available
data
(
for
potatoes
and
citrus)
for
use
in
the
dietary
exposure
assessments,
since
they
reflect
exposures
closer
to
the
point
of
consumption
and
would
therefore
be
a
more
accurate
representation
of
actual
(
i.
e.,
dinner
plate")
dietary
exposure.
For
all
other
commodities,
field
trial
data
were
used
in
the
assessment,
but
residues
were
either
very
low
or
nondetectable
(
soybeans,
cottonseed,
peanuts,
dry
beans
and
coffee).
Sugarbeet
and
sugarcane
were
excluded
from
the
assessments,
since
aldicarb
residues
are
not
expected
in
the
processed
commodities
as
consumed;
the
tolerance
for
sorghum
was
used
in
the
assessment,
but
did
not
contribute
to
estimated
dietary
exposure
due
to
the
low
percent
crop
treated
(%
CT),
the
low
tolerance,
and
low
consumption.

Use
information
for
aldicarb
has
been
summarized
in
two
Quantitative
Usage
Analyses
(
QUAs)
generated
by
the
Biological
and
Economic
Analysis
Division
(
BEAD),
dated
12/
99
and
5/
00.
The
use
information,
including
distinctions
in
%
CT
estimates
for
fresh
vs.
processed
potatoes,
oranges
and
grapefruit,
was
included
in
the
dietary
exposure
analyses
along
with
extensive
processing/
cooking
data,
generally
indicating
reduction
of
residues
through
boiling
and
juicing.
Since
aldicarb
is
systemic,
typical
food
preparation
practices
such
as
washing
and
peeling
are
not
expected
to
significantly
reduce
residues.

Estimated
acute
dietary
(
food
only)
exposure
and
risk
exceed
HED's
level
of
concern
[
i.
e.,
>
100
%
aPAD]
for
children
1­
2
years
and
children
3­
5
years
old
when
compared
to
the
rat
RBC
ChEI
endpoint.
The
estimated
dietary
exposure
and
risk
for
these
two
population
subgroups
at
the
99.9th
percentile
of
exposure
was
0.000797
mg/
kg/
day,
or
159%
aPAD
and
0.000643
mg/
kg/
day
or
129%
aPAD,
respectively.
For
the
general
US
population,
estimated
dietary
exposure
was
0.000358
mg/
kg/
day,
or
72%
aPAD.
Estimated
exposure
and
risk
were
below
HED's
level
of
concern
(
i.
e.,
<
100
%
aPAD)
at
the
99.8th
percentile
for
both
children
1­
2
years
old
and
children
3­
5
years
old.
If
the
PAD
is
based
on
the
rat
brain
ChEI
or
human
RBC
ChEI
endpoint,
risks
estimates
are
above
HED's
level
of
concern
for
children
1­
2
years
old
(
106%
and
122%,
respectively).
Page
12
of
51
Because
estimated
dietary
(
food
only)
exposure
was
above
HED's
level
of
concern,
an
analysis
was
conducted
to
determine
the
foods
or
food
forms
which
contribute
the
most
to
the
exposure
estimates.
For
all
population
subgroups,
residues
in
potatoes
were
the
most
significant
source
of
dietary
exposure.
Sensitivity
analyses
showed
that
actual
detected
residues
from
monitoring
are
the
source
of
the
estimated
exposure
and
risk,
and
not
assumed
residues
for
nondetects
in
the
monitoring
data
sets.
For
example,
in
a
sensitivity
analysis
which
assumed
aldicarb
per
se
residues
of
0
ppm
in
all
potato
and
citrus
commodities,
and
zero
residues
for
citrus
nondetects,
the
risk
for
the
general
US
population
was
reduced
to
154
%
aPAD;
for
children
1­
2
years
old,
the
estimated
risk
was
reduced
to
70
%
aPAD
at
the
99.9%
ile
of
exposure
when
compared
to
the
rat
RBC
ChEI
endpoint.

HED
was
requested
to
consider
the
impact
of
proposed
label
amendments
for
potatoes
and
citrus
as
well
as
a
proposed
import
tolerance
for
residues
in
bananas.
The
registrant
has
proposed
a
citrus
crop
group
tolerance,
a
decreased
pre­
harvest
interval
(
PHI)
on
potatoes
in
the
Pacific
Northwest,
and
use
on
potatoes
in
six
states
in
the
Midwest.
The
label
amendments
are
supported
by
adequate
residue
data
and
tolerances,
but
would
lead
to
increased
dietary
exposure
to
aldicarb
residues,
solely
on
the
basis
of
increased
acres
treated
(
i.
e.,
assuming
residues
in
potatoes
would
be
equivalent
to
existing
monitoring
data).
Although
a
tolerance
would
technically
be
required
for
the
proposed
food
use
on
imported
bananas,
the
application
technique
has
been
demonstrated
to
result
in
no
detectable
aldicarb
residues
in
whole
bananas,
peel,
pulp,
chips
and
puree
over
multiple
years
of
use
and
therefore
would
not
alter
the
risk.

Aldicarb
Exposure
from
Drinking
Water
The
OPP
Environmental
Fate
and
Effects
Division
(
EFED)
prepared
the
drinking
water
assessment
for
aldicarb
reregistration.
Aldicarb
has
the
potential
to
reach
surface
and
ground
water
sources
of
drinking
water
following
applications
in
agricultural
settings.
The
environmental
fate
database
for
aldicarb
and
its
degradates
(
sulfoxide
and
sulfone)
is
incomplete
but
adequate
for
characterizing
the
potential
for
aldicarb
residues
to
reach
and
to
persist
in
ground
and
surface
water
sources
of
drinking
water.

Total
aldicarb
residues
(
i.
e.,
aldicarb
plus
the
sulfoxide
and
sulfone
degradates)
are
persistent
and
mobile
in
most
soil
types.
The
environmental
profile
is
similar
to
that
observed
in
plants,
which
consists
of
rapid
oxidation
of
the
parent
aldicarb
to
aldicarb
sulfoxide
and
sulfone,
followed
by
breakdown
to
the
relatively
non­
toxic
non­
carbamate
residues.
The
degradates
are
more
soluble
in
water
than
the
parent.

For
the
purpose
of
the
drinking
water
assessment,
ground
water
concentrations
were
reported
in
eight
distinct
regions
selected
based
on
broad
similarity
in
aldicarb
usage,
crop
type
or
soil
conditions.
A
single
maximum
sample
result
detected
within
a
region
during
the
last
5
to
10
years
was
chosen
to
represent
ground
water
concentrations
within
that
entire
region.
The
aldicarb
water
residue
values
chosen
for
the
drinking
water
assessment
are
considered
somewhat
conservative
because
they
reflect
exposures
of
people
who
are
the
most
highly
exposed
in
each
region.
The
population
potentially
exposed
at
these
levels
consists
of
individuals
who
obtain
drinking
water
from
private
wells
in
areas
with
vulnerable
soils
or
that
may
be
contaminated
from
past
agricultural
applications
of
aldicarb.
Representative
aldicarb
residues
(
i.
e.,
aldicarb
and
plus
degradates)
in
ground
water
in
the
eight
regions
range
from
0
(
zero)
to
24
ppb.

Surface
water
monitoring
data
for
aldicarb
and
its
metabolites
are
limited,
especially
when
compared
Page
13
of
51
with
the
quantity
of
ground
water
monitoring
data.
Since
surface
water
monitoring
data
for
aldicarb
were
too
limited
to
be
used
quantitatively
in
the
drinking
water
exposure
assessment,
EFED
used
Tier­
II
modeling
to
generate
estimated
environmental
concentrations
(
EECs)
in
surface
water.
Specifically,
the
Pesticide
Root
Zone
Model
and
Exposure
Analysis
Model
System
(
PRZM/
EXAMS)
Index
Reservoir
was
used
to
generate
surface
water
EECs
for
drinking
water.

Aldicarb
Exposure
from
Tobacco
Since
aldicarb
is
registered
for
use
on
tobacco,
HED
conducted
an
inhalation
risk
assessment
for
adult
smokers.
The
estimate
of
exposure
was
generated
using
high­
end
residues
in
smoke
from
aldicarbtreated
tobacco,
conservative
assumptions
with
respect
to
the
frequency
of
smoking,
and
assuming
that
all
of
the
aldicarb
residue
in
smoke
is
absorbed
(
i.
e.,
none
of
the
residue
is
exhaled
along
with
the
smoke).
Short­
term
inhalation
MOEs
for
aldicarb
from
the
use
of
tobacco
are
estimated
to
be
160
for
females
and
187
for
males;
these
MOEs
are
greater
than
the
target
MOE
of
20,
indicating
that
exposure
and
risk
from
aldicarb
residues
in
tobacco
are
not
of
concern.
These
estimates
are
based
on
very
conservative
assumptions,
and
may
overestimate
exposure
through
this
route.

Aldicarb
Aggregate
Exposure
and
Risk
Aggregate
acute
risk
estimates
exceed
HED's
level
of
concern
regardless
of
the
endpoint
selected.
Acute
aggregate
risk
assessments
for
adults
and
children
include
combined
exposure
to
aldicarb
through
food
and
water.

Acute
dietary
exposure
and
risk
from
food
alone
was
above
HED's
level
of
concern
(
i.
e.,
>
100%
aPAD),
so
a
drinking
water
only
assessment
was
conducted.
If
all
of
the
allowable
exposure
occurred
through
drinking
water,
HED
would
have
concerns
for
acute
exposure
to
aldicarb
residues
in
surface
water.
It
should
be
noted
that
aldicarb
was
not
considered
to
have
a
high
potential
to
contaminate
surface
waters.
Acute
aggregate
risks
for
infants,
the
most
highly
exposed
population
subgroup,
range
from
1%
aPAD
from
modeling
use
on
potatoes
to
15%
aPAD
from
modeling
use
on
cotton
at
the
95th
%
ile
of
exposure.
Acute
aggregate
risks
for
the
general
US
population
and
all
other
population
subgroups
ranged
from
<
1%
aPAD
to
7%
aPAD.
The
%
PADs
are
based
on
the
rat
RBC
ChEI
endpoint.

Seven
regional
ground
water
monitoring
residue
levels
were
used
to
derive
an
acute
dietary
exposure
estimate
for
water
alone
(
the
eighth
region
had
a
residue
value
of
0
ppb,
and
was
excluded
from
the
aggregate
assessment).
Acute
aggregate
risks
for
infants,
the
most
highly
exposed
population
subgroup,
range
from
83%
aPAD
to
945%
aPAD
at
the
95th
%
ile
of
exposure.
Acute
aggregate
risks
for
the
general
US
population
and
all
other
population
subgroups
ranged
from
20%
aPAD
to
393%
aPAD.

Acute
aggregate
risks
calculated
based
on
ground
water
monitoring
values
overestimate
risks
for
all
but
those
who
obtain
their
drinking
water
from
wells
in
vulnerable
aldicarb
use
areas.
However,
since
acute
food
only
exposures
exceed
the
aPAD,
HED
is
concerned
about
any
additional
exposure
(
to
all
subpopulations)
through
drinking
water,
regardless
of
the
source.

Aldicarb
Occupational
Exposure
and
Risk
Page
14
of
51
The
occupational
risk
assessment
for
aldicarb
is
based
on
potential
exposure
to
agricultural
workers
during
loading
and
application
of
granular
products.
Aldicarb
is
applied
early
in
the
growing
season,
and
labels
require
immediate
soil
incorporation
of
granules;
postapplication
exposures
are
not
expected
for
workers,
so
a
quantitative
postapplication
risk
assessment
has
not
been
conducted.
Two
basic
occupational
handler
scenarios,
loading
granules
and
applying
granules,
were
assessed
using
unit
exposures
derived
from
a
chemical­
specific
study
conducted
by
the
registrant
(
MRID
438525­
01)
and
PHED
(
Pesticide
Handlers
Exposure
Database).
The
study
is
chemical­
and
formulation­
specific
in
that
it
used
aldicarb
low­
dust
granules
(
i.
e.,
corn
cob
&
gypsum)
which
are
the
only
commercially
marketed
products.
The
study
quantified
exposures
from
open
loading
and
open
cab
tractor
application
activities.
The
Agency
considers
this
study
more
representative
of
exposures
for
these
activities
instead
of
PHED
by
the
Agency
because
PHED
exposure
estimates
are
based
on
the
use
of
more
friable
clay
granules
instead
of
the
low­
friability
aldicarb
products
(
i.
e.,
PHED
exposures
are
based
on
formulations
that
contain
more
dust
than
available
aldicarb
products
which
would
be
expected
to
lead
to
higher
exposures).
Aldicarb
is
also
marketed
in
Lock­
n­
Load
closed
systems
and
can
also
be
applied
using
closed
cab
tractors.
The
study
did
not
quantify
the
exposures
associated
with
the
use
of
these
types
of
engineering
controls
so
PHED
was
used
to
evaluate
these
scenarios
due
to
a
lack
of
chemical­
and
formulation­
specific
data.
[
Note:
Exposure
values
for
both
PHED
and
MRID
438525­
01
are
similar
in
most
instances
and
in
most
cases
are
lower
for
MRID
438525­
01.
It
should
also
be
pointed
out
that
low
friability
granules
can
also
be
considered
an
engineering
control.]

Risks
were
of
not
concern
for
most
exposure
scenarios
based
on
the
aldicarb
specific
worker
exposure
data
for
loaders
and
applicators
(
MRID
438525­
01),
regardless
of
which
hazard
endpoint
was
considered
(
i.
e.,
rat
RBC,
rat
brain,
or
human).
In
only
a
few
instances
for
loaders
were
risks
identified
that
were
of
concern
based
on
this
study.
Loader
risks
based
on
the
rat
RBC
endpoint
(
i.
e.,
MOEs
=
13.6
&
16.4
for
80
acres
at
~
5+
lb
ai/
acre)
and
the
human
endpoint
(
i.
e.,
MOE
=
8.8
for
80
acres
at
6
lb
ai/
acre)
were
just
slightly
below
the
risk
targets
(
i.
e.,
MOEs
=
20
&
10,
respectively).
If
unit
exposures
from
PHED
are
considered,
the
results
are
similar
for
loaders
in
that
risks
were
not
of
concern
for
most
exposure
scenarios
regardless
of
which
hazard
endpoint
was
considered
(
i.
e.,
rat
RBC,
rat
brain,
or
human).
In
only
a
few
instances
for
loaders
based
on
PHED
were
risks
identified
that
were
of
concern.
Loader
risks
based
on
the
rat
RBC
endpoint
(
i.
e.,
MOEs
=
14.4
&
17.5
for
80
acres
at
~
5+
lb
ai/
acre)
and
the
human
endpoint
(
i.
e.,
MOE
=
9.4
for
80
acres
at
6
lb
ai/
acre)
were
just
slightly
below
the
risk
targets
(
i.
e.,
MOEs
=
20
&
10,
respectively).
For
applicators
based
on
PHED
data,
the
trend
is
very
different
from
that
observed
with
the
study
data
in
that
risks
were
of
concern
for
all
scenarios
considered
(
i.
e.,
MOEs
range
from
<
1
to
8.2).
There
are
two
key
factors
that
should
be
considered
in
the
interpretation
of
these
results
including
(
1)
exposures
for
open
loading
and
open
cabs
are
based
on
a
chemical­
specific
study
that
mirrors
how
aldicarb
is
packaged,
handled
and
used
in
agriculture
and
(
2)
a
dermal
absorption
factor
of
100
percent
has
been
used
and
if
that
factor
changed,
risks
would
also
change
proportionately.

Aldicarb
Incident
Review
HED
conducted
a
review
of
occupational
and
non­
occupational
incidents
as
reported
in
the
Incident
Data
System
(
IDS)
from
1996
through
1999
and
in
Poison
Control
Center
(
PCC)
data
generated
from
1993
to
1998.
Several
incidents
were
reported
from
use
in
occupational
settings.
During
this
time,
a
total
of
15
men
were
reported
to
be
adversely
exposed
to
aldicarb
in
occupational
Detailed
information
about
these
incidents
are
discussed
in
the
Incident
Data
section
of
this
document.
Page
15
of
51
Aldicarb
Data
Gaps
and
Labeling
Toxicology:

870.3200
21­
day
dermal
toxicity
(
including
RBC/
plasma/
brain
ChEI
measures).
28­
day
inhalation
study
(
including
RBC/
plasma/
brain
ChEI
measures).

Residue
Chemistry:

860.1500
Field
trials
in
sorghum
forage
and
cotton
gin
by­
products
(
gin
trash).
[
HED
recommends
cotton
field
trials
include
residues
in
cottonseed,
since
the
available
data
for
this
commodity
are
limited
and
of
poor
quality.]

Label
Changes:

Registered
labels
must
reflect
maximum
seasonal
use
rates
(
where
applicable).

The
restriction
against
feeding
grain
sorghum
forage
must
be
removed.

A
10­
month
plantback
interval
(
PBI)
should
be
specified
on
EPA
Reg.
No.
264­
331
for
crops
not
listed
on
the
label.
Page
16
of
51
2.0
PHYSICAL/
CHEMICAL
PROPERTIES
Technical
aldicarb
is
a
white
crystalline
solid
with
a
melting
point
of
98­
100
C
and
a
slight
sulfurous
odor.
Crystalline
aldicarb
is
heat­
sensitive
and
decomposes
above
100
C.
Aldicarb
is
soluble
in
water
(
0.6%)
and
increasingly
more
soluble
in
the
following
solvents:
hexane
(<
1%),
carbon
tetrachloride
(
4%),
benzene
(
18%),
methylethyl
ketone
(
20%),
acetone
(
38%),
and
chloroform
(
42%).
The
vapor
pressure
of
technical
aldicarb
is
2.9
x
10­
5
mm
Hg
at
25
C.
Identifying
codes
and
characteristics
are:

Empirical
Formula:
C7H14N2O2S
Molecular
Weight:
190.3
CAS
Registry
No.:
116­
06­
3
Chemical
ID
No.:
098301
Octanol/
water
partition
coefficient
(
log
Kow):
1.359
Density
(
at
25
C):
1.195
Structures
of
aldicarb
and
its
two
regulated
metabolites,
aldicarb
sulfoxide
and
aldicarb
sulfone,
are
shown
below:

Aldicarb:
2­
Methyl­
2­
(
methylthio)
propionaldehyde
O­
(
methyl
carbamoyl)
oxime
Aldicarb
sulfoxide:
2­
Methyl­
2­
(
methylsulfinyl)
propionaldehyde
O­(
methyl
carbamoyl)
oxime
Aldicarb
sulfone:
2­
Methyl­
2­
(
methylsulfonyl)
propionaldehyde
O­(
methyl
carbamoyl)
oxime
3.0
HAZARD
ASSESSMENT
3.1
Hazard
Profile
Aldicarb
is
a
N­
methyl
carbamate
pesticide
that
exerts
its
pesticidal
activity
and
elicits
adverse
toxic
effects
by
inhibition
of
cholinesterase
activity
[
ChEI],
which
has
been
demonstrated
in
whole
blood,
plasma,
red
blood
cells,
and
brain
of
rats,
mice,
and
dogs
following
acute,
subchronic,
and
chronic
exposure
and
in
plasma
and
RBC
in
humans
following
acute
exposure.

The
available
data
indicate
a
peak
effect
within
an
hour
of
dosing
followed
by
recovery
within
24
hours.
As
a
result,
a
comparable
degree
of
inhibition
occurs
whether
delivered
once
or
following
subchronic
or
chronic
dosing.

There
is
an
acute
oral
exposure
study
on
aldicarb
involving
direct
dosing
of
humans
in
which
plasma
and
RBC
cholinesterase
activity
and
clinical
signs
were
monitored.
There
is
also
a
full
database
of
oral
animal
toxicity
studies.

Aldicarb
is
highly
acutely
toxic
via
the
oral,
dermal,
and
inhalation
routes
of
exposure
in
the
acute
Page
17
of
51
studies
required
for
labeling
(
Toxicity
Category
I).
It
is
not
considered
to
be
a
dermal
sensitizer;
dermal
and
eye
irritation
studies
were
waived
due
to
severe
effects
(
death)
following
corneal
and
dermal
dosing.

Subchronic
toxicity
studies
demonstrate
that
aldicarb
inhibits
cholinesterase
activity
in
plasma,
red
blood
cells
(
RBC),
and
brain
in
dogs,
rats,
and
rabbits
following
exposure
by
the
oral
and
dermal
routes.
Clinical
signs
associated
with
cholinesterase
inhibition
(
ChEI)
observed
in
subchronic
studies
include
tremors,
salivation,
lacrimation,
lethargy,
and
prostration.
The
database
for
subchronic
toxicity
is
considered
incomplete
because
there
is
neither
an
acceptable
21
day
dermal
toxicity
study
nor
a
28­
day
inhalation
study.

The
database
for
chronic
toxicity
is
complete.
There
were
no
treatment­
related
effects
on
hematology,
clinical
chemistry
[
other
than
ChE
activity],
organ
weights,
and
histopathology.
Only
scattered
effects
on
other
measures
at
the
high
dose
were
noted,
such
as
decreased
body
weight
and
eye
effects
in
rats.

The
aldicarb
database
for
neurotoxicity
is
complete,
with
acceptable
acute,
subchronic,
and
developmental
neurotoxicity
studies.
In
addition,
there
is
a
published
acute
neurotoxicity
study
from
an
EPA
laboratory
on
the
comparative
sensitivity
of
young
and
adult
rats
following
acute
oral
exposures.
Both
the
acute
and
subchronic
rat
neurotoxicity
studies
show
a
variety
of
typical
clinical
signs
of
ChEI
after
oral
exposures,
including
decreased
motor
activity,
lacrimation,
tremors,
salivation,
pinpoint
pupils,
and
decreased
grip
strength,
as
well
as
significant
decreases
in
plasma,
RBC,
and
brain
cholinesterase
activity.
In
the
developmental
neurotoxicity
study
in
rats,
ChEI
and
associated
clinical
signs,
i.
e.,
tremors,
salivation,
lacrimation,
ataxia,
miosis,
and
hunched
posture,
were
observed
in
the
dams
at
the
same
dose
levels
where
decreased
motor
activity
was
observed
in
the
pups.
No
neuropathological
effects
related
to
exposure
were
seen
in
any
of
the
acute,
subchronic,
chronic,
or
neurotoxicity
studies.

There
was
no
indication
of
increased
susceptibility
of
offspring
in
rat
or
rabbit
developmental
toxicity
studies,
in
the
rat
reproduction
study,
or
in
a
rat
developmental
neurotoxicity
study.
In
the
developmental
toxicity
study
in
rabbits,
no
developmental
effects
were
observed
at
any
dose
level,
but
maternal
toxicity
was
observed,
as
evidenced
by
decreased
body
weight,
pale
kidneys,
and
hydroceles
on
the
oviducts.
In
the
developmental
toxicity
study
in
rats,
the
developmental
effects,
ecchymosis
(
hemorrhagic
spots)
of
the
trunk,
occurred
at
the
same
dose
level
as
the
maternal
effects,
decreased
body­
weight
gain
and
food
consumption.
Signs
of
ChEI
including
hypoactivity,
ataxia,
tremors,
lacrimation
and
cold
extremities
were
observed
in
the
maternal
rats.
In
the
reproduction
study,
the
effects
on
the
offspring,
reduced
survival
(
day
4)
and
decreased
body
weight,
were
observed
only
at
the
highest
dose
tested
where
parental
toxicity
occurred,
as
evidenced
by
decreased
body
weight
and
blood
cholinesterase
inhibition.
Maternal
toxicity
was
observed
at
a
dose
where
no
offspring
toxicity
was
observed
(
i.
e.,
the
NOAEL
for
maternal
toxicity
was
lower
than
the
offspring
NOAEL).

A
published
acute
oral
exposure
study
(
EPA/
ORD;
Moser)
reported
evidence
for
increased
sensitivity
of
young
rats.
The
only
parameter
that
demonstrated
sensitivity
was
brain
cholinesterase
inhibition
(
i.
e.,
the
magnitude
of
the
brain
ChEI
was
greater
in
the
young
rat
compared
to
the
adult
rat
at
comparable
acute
doses).
Decreased
motor
activity
was
observed
only
in
the
adult
animals,
and
clinical
signs
of
ChEI
occurred
more
frequently
in,
and
recovery
was
prolonged
in,
the
adult
compared
to
the
young
animal.
Sensitivity
with
respect
to
the
whole
blood
compartment
could
not
be
determined
since
whole
blood
ChEI
was
extremely
high
in
this
compartment
at
all
dose
levels
in
both
the
young
Page
18
of
51
and
adult
animal.

In
an
acute
oral
study
conducted
in
human
volunteers
of
both
sexes,
red
blood
cell
and
plasma
cholinesterase
activities
and
clinical
signs
were
monitored.
Aldicarb
treatment
of
both
males
and
females
resulted
in
statistically
significant
inhibition
of
both
red
blood
cell
and
plasma
cholinesterases
at
the
two
common
dose
levels.
The
inhibition
observed
at
the
lowest
dose,
which
was
tested
only
in
males,
was
not
considered
toxicologically
significant
in
males.
However,
there
is
a
lack
of
doseresponse
information
in
females
at
the
low
dose
level.
The
results
of
the
acute
oral
human
study
suggest
a
two­
fold
differences
in
toxic
responses
between
animals
and
humans.
This
study
was
evaluated
by
the
HSRB,
and
they
arrived
at
similar
conclusions.

Aldicarb
is
rapidly
absorbed,
widely
distributed,
and
rapidly
excreted,
with
more
than
90%
excreted
in
the
urine
within
24
hours
after
either
acute
or
repeated
oral
doses.
It
is
metabolized
primarily
to
aldicarb
sulfoxide,
with
a
smaller
amount
then
slowly
converted
to
aldicarb
sulfone.
These
three
moieties
(
aldicarb,
sulfoxide,
and
sulfone)
may
then
be
further
metabolized
to
oximes
and
nitriles.
Both
the
sulfoxide
and
sulfone
are
also
potent
cholinesterase
inhibitors.
The
sulfone
is
less
toxic
following
an
acute
oral
exposure
than
either
the
parent
compound
or
the
sulfoxide
which
show
comparable
acute
oral
toxicity,
based
on
results
of
median
lethal
dose
studies
(
i.
e.,
LD50'
s).

There
are
acceptable
negative
studies
for
all
three
required
categories
of
mutagenic
effects:
gene
mutations,
chromosomal
aberrations,
and
other
genotoxic
effects.
Aldicarb
was
negative
in
the
in
vitro
forward
gene
mutation
assay,
in
the
in
vivo
chromosomal
aberration
assay
in
mouse
bone
marrow
cells,
in
the
dominant
lethal
assay,
and
in
the
unscheduled
DNA
synthesis
assay.
Based
on
these
studies,
aldicarb
is
not
considered
mutagenic.

Aldicarb
is
classified
as
Category
E,
Evidence
of
Non­
Carcinogenicity
for
Humans,
based
on
the
lack
of
evidence
of
carcinogenicity
in
studies
in
rats
and
mice
and
the
absence
of
a
mutagenicity
concern.

There
are
no
acceptable
dermal
toxicity
or
dermal
dermal
penetration
studies
that
can
be
used,
when
considered
with
all
available
oral
studies,
to
estimate
dermal
absorption
for
occupational
exposure
and
risk
assessments.
In
this
risk
assessment,
toxicity
by
the
dermal
route
has
been
considered
to
be
equivalent
to
toxicity
by
the
oral
route
of
exposure
(
100
%).
Additionally,
there
is
no
inhalation
toxicity
study,
and
toxicity
by
the
inhalation
route
also
has
been
considered
to
be
equivalent
to
toxicity
by
the
oral
route
of
exposure
(
100
%).
Table
2
summarizes
the
results
of
acute
toxicity
testing
for
aldicarb.

Table
2.
Aldicarb
Acute
Toxicity.

Guideline
No./
Study
Type
MRID
No.
Results
Tox
Category
870.1100
Acute
oral
toxicity
00057333
LD50
=
0.8
mg/
kg/
day
I
870.1200
Acute
dermal
toxicity
00091241
00069916
LD50
=
20
mg/
kg/
day,
water
LD50
=
5
mg/
kg,
propylene
glycol
I
870.1300
Acute
inhalation
toxicity
00069916
00057333
LC50
<
0.007
mg/
L
I
870.2400
Acute
eye
irritation
00069916
No
corneal
irritation
at
lethal
dose
N/
A
Page
19
of
51
Table
2.
Aldicarb
Acute
Toxicity.

Guideline
No./
Study
Type
MRID
No.
Results
Tox
Category
870.2500
Acute
dermal
irritation
00069916
None
at
fatal
levels
N/
A
870.2600
Skin
sensitization
N/
A
N/
A
N/
A
The
above
studies
satisfy
the
acute
toxicity
data
requirements
[
OPPTS
870.1100,
870.1200,
870.1300];
dermal
and
eye
irritation
studies
not
required
due
to
severe
effects
[
death]
following
eye
and
dermal
exposure;
(
N/
A
=
not
applicable).
Table
3
summarizes
the
toxicity
profile
for
technical
aldicarb.

Table
3.
Toxicity
Profile
of
Aldicarb
Technical.

Study
Type
[
GLN
No.]
MRID
No./
Classification
Results1
Sub­
chronic
oral
toxicity
(
dog)
[
870.3150]
41919901
(
1991)
Acceptable
NOAEL=
0.02
mg/
kg/
day
LOAEL=
0.06
mg/
kg/
day
Based
on
plasma
and
RBC
ChEI
in
males
and
females
Developmental
toxicity
rodent
(
rat)

[
870.3700a]
41004501
(
1988)
Guideline
Maternal:
NOAEL=
0.125
mg/
kg/
day
LOAEL=
0.25
mg/
kg/
day
Based
on
decreased
body
weight
gain
and
food
consumption
Developmental:
NOAEL=
0.125
mg/
kg/
day
LOAEL=
0.25
mg/
kg/
day
Based
on
ecchymosis
of
the
trunk
Developmental
toxicity
in
nonrodent
(
rabbit)
[
870.3700b]
0132668
(
1983)
Guideline
Maternal:
NOAEL=
0.1
mg/
kg/
day
LOAEL=
0.25
mg/
kg/
day
Based
on
decreased
body
weight,
pale
kidneys,
hydroceles
on
the
oviducts
Developmental:
NOAEL=>
0.5
mg/
kg/
day
Reproduction
and
fertility
effects
[
870.3800]
42148401
(
1991)
Minimum
Parental/
Systemic
NOAEL=
0.4
mg/
kg/
day
LOAEL=
0.7­
0.9
mg/
kg/
day
Based
on
decreased
body
weight
gains
and
RBC
and
plasma
ChEI
Reproductive:
NOAEL=
0.7­
0.9
mg/
kg/
day
LOAEL=
1.4­
1.7
mg/
kg/
day
Based
on
decreased
viability
and
body
weights,
and
signs
of
debilitation
Chronic
oral
toxicity
in
rodents
[
870.4100a]
43045401
(
1993)
Minimum
NOAEL=
0.047
mg/
kg/
day
LOAEL=
0.47
mg/
kg/
day
Based
on
plasma
and
RBC
ChEI
Chronic
oral
toxicity
dogs
[
870.4100b]
40695401,
42191501
(
1988)
Supplementary
NOAEL<
0.028
mg/
kg/
day
LOAEL=
0.028
mg/
kg/
day
Based
on
plasma
ChEI
Carcinogenicity
in
rats
[
870.4200]
43045401
(
1993)
Minimum
NOAEL=
0.047
mg/
kg/
day
LOAEL=
0.47
mg/
kg/
day
Based
on
plasma/
RBC
ChEI
No
evidence
of
carcinogenicity
Page
20
of
51
Table
3.
Toxicity
Profile
of
Aldicarb
Technical.

Study
Type
[
GLN
No.]
MRID
No./
Classification
Results1
Carcinogenicity
in
mice
[
870.4300]
00044732;
00044733;
00044734
(
1972)
Minimum
NOAEL=
0.2
mg/
kg/
day
LOAEL=
0.4
mg/
kg/
day
Based
on
increased
mortality.
No
evidence
of
carcinogenicity.

Gene
Mutation
[
870.5300]
00148168
(
1985)
Acceptable
1000­
5000
ug/
ml:
Negative
with
and
without
activation
at
a
marginally
cytotoxic
dose.

Cytogenetics:
Mammalian
bone
marrow
chromosome
aberration
test.
[
870.5385]
41661301;
41663102
(
1990)
Acceptable
0.1­
0.4
mg/
kg:
No
chromosomal
aberrations
in
mouse
bone
marrow
cells.

Unscheduled
DNA
Synthesis
[
870.5500]
00141673
(
1984)
Acceptable
33­
10,000
ug/
well:
No
effects.

Rat
Dominant
Lethal
Study
43575101
(
1995)
Acceptable
Systemic
LOAEL:
2.28
mg/
kg
Based
on
body
weight
reductions,
tremors,
and
plasma,
RBC
and
brain
ChEI.
No
evidence
of
a
dominant
lethal
effect.

Acute
neurotoxicity
screening
battery
[
870.6200a]
43442301
(
1994)
Acceptable
NOAEL<
0.05
mg/
kg/
day
LOAEL=
0.05
mg/
kg/
day
Based
on
plasma
ChEI.

Subchronic
neurotoxicity
screening
battery
[
870.6200b]
43829602
(
1995)
Acceptable
NOAEL<
0.05
mg/
kg/
day
LOAEL=
0.05
mg/
kg/
day
Based
on
pinpoint
pupils
and
blood
and
brain
ChEI.

Developmental
neurotoxicity
[
870.6300]
43829601
(
1995)
Acceptable
Maternal:
NOAEL=
0.05
mg/
kg/
day
LOAEL=
0.1
mg/
kg/
day
Based
on
plasma
ChEI
Offspring:
NOAEL=
0.05
mg/
kg/
day
LOAEL=
0.1
mg/
kg/
day
Based
on
reduced
body
weights
and
decreased
motor
activity
Metabolism
and
pharmacokinetics
[
870.7485]
00102022
(
1966)
00102023
(
1967)
85%
of
an
acute
oral
dose
to
rats
was
excreted
in
24
hours.
The
metabolism
of
aldicarb
was
primarily
to
the
sulfoxide
(
40%),
with
a
smaller
amount
then
slowly
converted
to
the
sulfone.

Special
neurotoxicity
studies:
Moser
VC
45068601
(
1999)
TAP
157
94­
106
NOAEL<
0.05
mg/
kg.
LOAEL=
0.05
mg/
kg
(
pups)
Effects
in
pups:
Blood
(
both
sexes),
brain
ChEI
(
males).
Note:
PND
17
day
pups
exhibited
twice
the
level
of
brain
ChEI
as
adults.

Acute
oral
study
(
human)
Inveresk
42373001
(
1992)
46131001
(
supplementary
report)
NOAEL
=
not
determined
for
females
LOAEL
=
0.01
mg/
kg
1NOAEL
=
No
observed
adverse
effects
level;
LOAEL
=
Lowest
observed
adverse
effects
level;
ChE
=
Cholinesterase;
ChEI
=
Cholinesterase
inhibition;
RBC
=
red
blood
cell.
Page
21
of
51
3.2
Dose
Response
Assessment
3.2.1
Benchmark
Dose
(
BMD)
Analysis
In
order
to
evaluate
the
appropriate
point
of
departure
(
PoD)
for
ChEI,
the
Agency
considered
benchmark
dose
(
BMD)
estimates
developed
from
several
studies
as
mentioned
above
along
with
BMD
estimates
provided
in
the
preliminary
cumulative
risk
assessment
for
the
N­
methyl
carbamates
(
USEPA,
2005).
Dose­
response
modeling
is
preferred
over
the
use
of
NOAEL/
LOAELs
(
i.
e.,
no
or
low
observed
adverse
effect
levels)
since
NOAELs
and
LOAELs
do
not
necessarily
reflect
the
relationship
between
dose
and
response
for
a
given
chemical,
but
instead
reflect
dose
selection
(
USEPA,
2000).
The
estimated
dose
at
which
10%
ChEI
is
observed
(
BMD10)
and
the
lower
95%
confidence
intervals
(
BMDL10)
were
estimated
by
fitting
the
ChE
data
to
an
exponential
doseresponse
model
using
generalized
nonlinear
least
squares.
The
BMD10
was
selected
because
it
is
generally
at
or
near
the
limit
of
sensitivity
for
discerning
a
statistically
significant
decrease
in
ChE
activity
across
the
blood
and
brain
compartments
and
is
a
response
level
close
to
the
background
ChE
activity.
Moreover,
the
Agency
believes
that
10%
is
likely
to
be
protective
for
other
toxicities,
such
as
clinical
signs
and/
or
behavioral
endpoints.

The
Agency's
BMD
analysis
for
the
preliminary
cumulative
risk
assessment
was
presented
to
the
FIFRA
SAP
in
February
and
August,
2005.
At
those
meetings,
the
panel
supported
the
Agency's
approach
for
developing
BMD
estimates
for
the
N­
methyl
carbamates.
In
the
current
analysis,
the
Agency
used
data
from
both
the
registrant's
dose­
response
studies
and
from
the
Agency's
comparative
study
(
adult
rat
data
only).
The
Agency
believes
that
use
of
data
from
multiple
studies
provides
a
more
robust
analysis
than
a
single
study.
The
results
of
the
combined
analysis
indicate
that
in
adult
rats,
RBC
ChE
inhibition
is
slightly
more
sensitive
than
brain
ChE
inhibition
(
ie,
BMDL10
0.02
mg/
kg
compared
to
0.03
mg/
kg;
respectively;
BMD10
0.03
mg/
kg
compared
to
0.05­
0.06
mg/
kg,
respectively).
Ratios
of
the
BMD10s
for
brain
ChE
inhibition
between
juvenile
and
adult
animals
suggest
that
juvenile
animals
are
2X
more
sensitive
than
adult
rats.
Therefore,
the
Agency
has
retained
a
2X
FQPA
safety
factor
in
the
derivation
of
the
aldicarb
acute
aPAD
and
other
acute
risk
assessments.

The
human
toxicity
study
for
aldicarb
does
not
provide
brain
ChE
data,
but
it
does
provide
RBC
and
plasma
ChE
data
for
both
males
and
females.
The
blood
ChE
activity
data
(
plasma
and
RBC)
provided
in
the
human
study
are
considered
appropriate
surrogate
measures
of
potential
effects
on
peripheral
nervous
system
(
PNS)
acethycholinesterase
(
AchE)
activity,
and
of
potential
effects
on
the
central
nervous
system
(
CNS)
when
brain
ChE
data
are
lacking
(
USEPA,
2000).
AchE
is
the
target
enzyme
for
the
cumulative
risk
assessment
and
is
the
primary
form
of
ChE
found
in
RBCs.
The
RBC
data,
therefore,
is
being
utilized
by
the
Agency
to
inform
the
pesticide­
specific
interspecies
extrapolation.

The
measured
RBC
ChE
activity
from
the
human
study
is
adequate
for
estimation
of
BMD
and
BMDLs.
The
RBC
ChE
data
from
the
aldicarb
human
study
was
utilized
in
the
model
in
the
same
manner
as
rat
data
(
brain
and
RBC)
that
are
available
for
the
NMCs
of
the
cumulative
hazard
assessment
(
USEPA
2005).
The
BMD10
and
BMDL10
estimates
for
both
rat
(
RBC,
brain)
and
human
(
RBC)
are
included
in
Table
4
below.
Page
22
of
51
Table
4.
Oral
BMD10s
and
BMDL10s
Generated
from
Adult
Rat
ChE
(
RBC,
brain)
and
Human
ChE
(
RBC)
Data
for
Aldicarb.

Rat
Human
Brain
RBC
RBC
Chemical
BMD10
(
mg/
kg)
BMDL10
(
mg/
kg)
BMD10
(
mg/
kg)
BMDL10
(
mg/
kg)
BMD10
(
mg/
kg)
BMDL10
(
mg/
kg)

Aldicarb
F=
0.05
M=
0.06
F=
0.03
M=
0.03
0.03
0.02
0.02
0.01
BMD
estimates
are
presented
as
a
single
estimate
when
there
are
no
differences
between
sexes.
Human
RBC
data
obtained
from
MRID
42373001
Rat
brain
and
RBC
data
obtained
from
MRIDs
43442302,
43442305,
43829601,
43829602,
45068601.

3.2.1
Endpoint
Selection
Based
on
the
toxicity
profile,
the
Agency
has
selected
endpoints
and
doses
for
assessment
of
risk.
The
Agency
considered
the
rat
acute
and
subchronic
neurotoxicity
studies
and
the
non­
guideline
neurotoxicity
study
(
Moser)
to
be
co­
critical
for
assessment
of
the
acute
exposure
scenarios.
Due
to
recovery
of
ChEI
within
24
hours
following
aldicarb
exposure,
the
use
of
the
subchronic
neurotoxicity
study
in
rats
for
endpoint
selection
is
considered
appropriate
and
protective
(
repeated
dosing
is
considered
a
series
of
acute
exposures).

There
are
several
studies
available
where
acute
ChE
inhibition
was
measured
at
or
near
peak
time
of
inhibition
(
45
minutes
 
1hour)
and
these
inform
the
derivation
of
the
acute
RfD
and
acute
PAD.
These
include
the
acute
and
subchronic
neurotoxicity
studies
performed
by
the
registrant
and
an
acute
comparative
ChE
activity
study
performed
by
scientists
from
the
National
Health
and
Environmental
Effects
Research
Laboratory
(
NHEERL).
Clinical
signs
were
also
reported
in
these
studies,
but
usually
only
at
the
higher
dose
levels;
i.
e.,
ChEI
occurred
at
doses
lower
than
or
equal
to
dose
levels
where
clinical
signs
occurred.
It
is
unknown
whether
changes
in
clinical
signs
indicative
of
ChEI
are
related
to
brain
or
peripheral
ChE
inhibition;
the
Agency
cannot
discount
the
potential
that
peripheral
ChE
inhibition
may
be
produced
by
aldicarb.
Given
that
numerous
studies
have
shown
RBC
ChE
inhibition
to
be
a
sensitive
measure
and
that
dose­
related
changes
in
behavioral
endpoints
and
clinical
signs
have
been
observed
at
the
higher
doses
of
aldicarb,
at
this
time,
the
Agency
considers
the
RBC
ChE
inhibition
data
from
the
animal
studies
to
be
sufficiently
reliable
for
developing
a
point
of
departure
for
risk
assessment
purposes.

For
aldicarb,
the
similarity
of
response
between
humans
and
rats
following
acute
oral
exposure
allows
for
the
use
of
both
sets
of
data
in
considering
toxicity
endpoint
selection
and
uncertainty
factors.
In
an
acute
oral
study
conducted
in
human
volunteers,
aldicarb
treatment
of
both
males
and
females
resulted
in
statistically­
significant
inhibition
of
both
red
blood
cell
and
plasma
cholinesterases
at
the
two
common
dose
levels.
Note
that
EPA's
use
of
a
human
toxicity
study
in
the
aldicarb
risk
assessment
is
in
accordance
with
the
Agency's
Final
Rule
promulgated
on
January
26,
2006,
related
to
Protections
for
Subjects
in
Human
Research,
which
is
codified
in
40
CFR
Part
26.

There
are
no
suitable
dermal
or
inhalation
toxicity
or
dermal
penetration
studies
for
aldicarb
risk
assessment.
Therefore
the
same
studies
are
considered
appropriate
for
endpoint
selection
for
short
and
intermediate
term
occupational
dermal
and
inhalation
exposure.
Page
23
of
51
Additionally,
based
on
the
recovery
of
effects
within
24
hours
seen
in
both
the
human
and
animal
studies
and
on
the
fact
that
dosing
in
the
subchronic
neurotoxicity
study
in
rats
and
special
neurotoxicity
study
are
considered
a
series
of
acute
exposures,
the
same
toxicity
studies
were
considered
for
establishing
a
chronic
RfD
and
for
assessing
long­
term
occupational
risk.
However,
the
Agency
has
determined
that
a
chronic
risk
assessment
is
not
needed,
since
risks
resulting
from
aldicarb
exposure
are
better
described
as
a
series
of
acute
risks.

The
registrant
submitted
rat
21­
day
and
5­
day
dermal
toxicity
studies
in
which
the
granular
formulation
containing
14.75
%
ai
was
used
as
the
test
substance,
rather
than
the
technical
active
ingredient.
These
studies
had
inconsistent
findings
with
respect
to
body
weight
gains
and
ChEI
data,
and
were
considered
unacceptable
for
the
purpose
of
risk
assessment.
HED
had
concerns
about
the
extent
of
wetting
of
the
skin,
as
well
as
the
percentage
of
body
surface
area
treated,
which
may
have
contributed
to
the
lack
of
a
dose­
response.
The
Hazard
Identification
Assessment
Review
Committee
(
HIARC)
discussed
the
data
from
these
two
studies,
along
with
ChEI
data
from
oral
studies
of
varying
durations,
in
order
to
determine
if
a
weight­
of­
evidence­
based
dermal
absorption
factor
could
be
derived.
Although
the
HIARC
agreed
that
most
of
the
data
suggest
a
dermal
absorption
factor
of
less
than
100%,
inconsistencies
in
the
data
and
methodology
concerns
prevented
departure
from
the
use
of
100%
absorption
for
dermal
exposure
assessments.
Although
this
value
is
thought
to
be
conservative
and
is
likely
to
overestimate
risks
from
dermal
exposures
to
aldicarb,
it
is
protective.

Likewise,
for
inhalation
exposures
assessed
using
oral
studies,
the
HIARC
selected
an
inhalation
absorption
factor
of
100%
relative
to
oral
exposures
to
be
applied
in
assessing
inhalation
exposure
and
risk
for
aldicarb.
Table
5
presents
the
toxicity
endpoints
for
risk
assessment.

Table
5.
Aldicarb
Toxicology
Endpoint
Selection.

Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF1
Hazard­
Based
FQPA
SF
and
Endpoint
for
Risk
Assessment
Study
and
Toxicological
Effects
DIETARY
EXPOSURES
Acute
Dietary:
General
US
Population
[
MRID
Nos.
43829602,
45068601,
43442302,
43442305,
&
42373001]
BMDL10
=
0.02
mg/
kg
UF
=
20
Acute
RfD
=
0.001
mg/
kg/
day
FQPA
SF
=
2X
aPAD=
acute
RfD
FQPA
SF
=
0.0005
mg/
kg/
day
Rat
acute/
subchronic
neurotoxicity
(
adult)
RBC
ChEI
human
study
[
reduction
of
interspecies
factor
to
2X]
Chronic
Dietary:
General
US
Population
[
MRID
No.
43829602,
45068601,
43442302,
43442305,
&
42373001]
BMDL10
=
0.02
mg/
kg
UF
=
20
Chronic
RfD
=
0.001
mg/
kg/
day
FQPA
SF
=
2X
cPAD
=
chronic
RfD
FQPA
SF
=
0.0005
mg/
kg/
day
Rat
acute/
subchronic
neurotoxicity
(
adult)
RBC
ChEI
human
study
[
reduction
of
interspecies
factor
to
2X]
Page
24
of
51
Table
5.
Aldicarb
Toxicology
Endpoint
Selection.

Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF1
Hazard­
Based
FQPA
SF
and
Endpoint
for
Risk
Assessment
Study
and
Toxicological
Effects
DERMAL
EXPOSURES2
[
Occupational]
Short­
Term
(
1­
30
days);
Intermediate­
Term
(
30
days
to
several
months)

[
MRID
No.
43829602,
45068601,
43442302,
43442305,
&
42373001]
Oral
study
BMDL10
=
0.02
mg/
kg
Absorption
factor
=
100%
LOC
for
MOE
=
20
Rat
acute/
subchronic
neurotoxicity
(
adult)
RBC
ChEI
human
study
[
reduction
of
interspecies
factor
to
2X]
INHALATION
EXPOSURES2
[
Occupational]
Any
Duration
[
MRID
No.
43829602,
45068601,
43442302,
43442305,
&
42373001]
Oral
study
BMDL10
=
0.02
mg/
kg
Absorption
factor
=
100%
LOC
for
MOE
=
20
Rat
acute/
subchronic
neurotoxicity
(
adult)
RBC
ChEI
human
study
[
reduction
of
interspecies
factor
to
2X]
1
The
UF
10X
is
for
intraspecies
variability
2
Appropriate
route­
to­
route
extrapolation
should
be
performed
for
these
risk
assessments.
For
both
dermal
and
inhalation
risks,
a
100%
absorption
factor
should
be
used
to
convert
relevant
exposure
estimates
to
equivalent
oral
doses
and
compared
to
the
oral
LOAEL.

For
informational
purposes,
Table
6
shows
aPADs
using
the
rat
brain
and
human
RBC
BMDL10
for
comparison
with
the
aPAD
based
on
the
rat
RBC
BMDL10.

Table
6
Rat3
Human4
Brain
RBC
RBC
Parameter
BMD10
(
mg/
kg)
1
F=
0.05
M=
0.06
0.03
0.02
BMDL10
(
mg/
kg)
2
0.03
0.02
0.013
UF
(
intraspecies)
10X
10X
10X
UF
(
interspecies)
2X
2X
1X
FQPA
SF
2X
2X
2X
Acute
RfD
0.0015
0.001
mg/
kg
0.001
Acute
PAD
0.00075
0.0005
mg/
kg
0.00065
1.
BMD
estimates
are
presented
as
a
single
estimate
when
there
are
no
differences
between
sexes.
2.
BMDL10
used
for
risk
assessment
3.
Human
RBC
data
obtained
from
MRID
42373001
4.
Rat
brain
and
RBC
data
obtained
from
MRIDs
43442302,
43442305,
43829601,
43829602,
45068601.
Page
25
of
51
3.3
FQPA
Considerations
There
was
no
evidence
of
increased
sensitivity
in
any
of
the
guideline
studies
reviewed.
Aldicarb
did
not
result
in
developmental
toxicity
in
either
rats
or
rabbits
or
in
reproductive
effects
in
the
rat
multi­
generation
reproduction
study.
Additionally,
there
was
no
developmental
toxicity
in
the
developmental
neurotoxicity
study
in
rats.
However,
the
comparative
ChE
inhibition
study
[
Moser]
demonstrated
that
pups
were
more
sensitive
than
the
adults
with
respect
to
brain
ChEI.
Based
on
benchmark
dose
(
BMD)
estimates
calculated
from
these
data,
the
pups
are
2X
more
sensitive
than
the
adults
[
brain
BMD10s
ranged
from
0.014
to
0.020
in
juvenile
animals
and
0.024
to
0.031
in
adult
animals].
Therefore,
a
FQPA
safety
factor
of
2X
is
retained.

3.4
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
aldicarb,
there
was
no
estrogen,
androgen,
and/
or
thyroid
mediated
toxicity.

When
additional
appropriate
screening
and/
or
testing
protocols
being
considered
under
the
Agency's
EDSP
have
been
developed,
aldicarb
may
be
subjected
to
further
screening
and/
or
testing
to
better
characterize
effects
related
to
endocrine
disruption.

4.0
EXPOSURE
ASSESSMENT
AND
CHARACTERIZATION
4.1
Summary
of
Registered
Uses
Aldicarb
is
a
carbamate
pesticide
which
is
registered
for
use
as
a
systemic
insecticide,
acaricide
and
nematicide
on
agricultural
crops
including
citrus,
cotton,
dry
beans,
peanuts,
pecans,
potatoes,
sorghum,
soybeans,
sugar
beets,
sugarcane,
sweet
potatoes,
and
seed
alfalfa
(
CA).
In
addition,
aldicarb
may
be
applied
to
field
grown
ornamentals
(
CA)
and
tobacco,
and
on
coffee
grown
in
Puerto
Rico.
The
types
of
plant
pests
controlled
by
aldicarb
include
leaf
phylloxera;
bud
moth;
citrus
nematode;
aphids;
mites
(
citrus
red,
citrus
rust,
Texas
citrus);
white
flies;
thrips;
fleahoppers,
leafminers;
leafhoppers;
overwintering
boll
weevil
(
adults
feeding
on
foliage);
lygus;
nematodes;
cotton
leaf
perforator;
seedcorn
maggot;
Mexican
bean
beetle;
flea
beetles;
Colorado
potato
beetle;
greenbug;
chinch
bug;
three
cornered
alfalfa
hopper
Page
26
of
51
(
suppression);
and
sugar
beet
root
maggot.

Aldicarb
is
a
restricted
use
pesticide
(
RUP),
and
may
be
applied
only
in
occupational
settings
by
certified
applicators.
There
are
no
products
containing
the
active
ingredient
aldicarb
which
are
intended
for
sale
to
homeowners
or
in
non­
occupational
settings
(
e.
g.,
turf
or
golf
course).

Aldicarb
is
formulated
and
marketed
solely
as
a
granular
pesticide.
Aldicarb
in
a
vinyl
binder
coating
is
adhered
to
either
a
corn
cob
grit
or
gypsum
substrate;
these
two
substrates
produce
less
dust
than
typical
clay
substrates
used
for
granular
pesticides.
Only
the
gypsum
granular
is
available
in
closed
loading
systems.
The
formulations
consist
of
5,
10
and
15%
granulars,
which
are
applied
early
in
the
growing
season,
either
pre­
plant,
at­
planting,
or
early
postemergent
using
ground
application
equipment.
Labels
specify
use
of
positive
displacement
application
equipment
and
immediate
soil
incorporation.

For
most
crops,
only
one
aldicarb
application
per
season
is
allowed,
but
2
or
3
split
applications
are
permitted
on
sugar
beets.
The
pre­
harvest
intervals
(
PHIs)
are
generally
long
due
to
the
early
application
timing,
ranging
from
80
to
150
days
when
specified.

Use
information
for
aldicarb
has
been
summarized
in
two
Quantitative
Usage
Analyses
(
QUAs)
generated
by
BEAD/
OPP,
dated
12/
99
and
5/
00.
Estimates
of
the
amount
of
active
ingredient
applied
on
a
crop­
specific
basis
have
been
provided
based
on
data
from
EPA,
USDA,
the
National
Center
for
Food
and
Agricultural
Policy,
and
the
WEFA
group.
In
terms
of
pounds
of
active
ingredient
(
ai)
applied,
the
most
significant
use
site
for
aldicarb
is
cotton,
with
2
to
3
million
lbs
ai
applied
on
an
annual
basis.
Other
significant
use
sites
(
in
decreasing
amounts
of
ai
applied)
are
peanuts,
potatoes,
sugar
beets
and
oranges.
Based
on
acres
grown
and
pounds
active
ingredient
applied,
BEAD
generates
estimates
of
the
percent
of
crop
treated
(%
CT)
for
use
in
HED's
dietary
exposure
analyses.
For
aldicarb,
crops
with
%
CT
estimates
of
greater
than
20%
are
peanuts,
sweet
potatoes,
cotton,
potatoes
and
citrus.

4.2
Dietary
Exposure/
Risk
Pathway
Potential
dietary
(
food
only)
exposure
to
aldicarb
can
occur
following
application
to
food
crops
including
pecans;
potatoes;
sweet
potatoes;
cotton;
dry
beans;
grain
sorghum;
soybeans;
sugar
beets;
sugarcane;
peanuts;
citrus
(
orange,
grapefruit,
lemon
and
lime);
and
coffee.

4.2.1
Residue
Profile
The
aldicarb
residue
chemistry
database
is
largely
complete
and
is
considered
adequate
to
reassess
most
tolerances
listed
in
40
CFR
§
180.269.
The
regulated
residues
are
the
combined
residues
of
aldicarb
and
its
two
cholinesterase­
inhibiting
metabolites
aldicarb
sulfoxide
[
2­
methyl­
2­(
methylsulfinyl)
propionaldehyde
O­(
methyl
carbamoyl)
oxime]
and
aldicarb
sulfone
[
2­
methyl­
2­(
methylsulfonyl)
propionaldehyde
O­(
methyl
carbamoyl)
oxime].
Aldicarb
sulfoxide
is
considered
to
have
similar
potency
to
the
parent
in
terms
of
toxicity,
while
aldicarb
sulfone
is
less
potent.
Aldicarb
and
the
sulfoxide
and
sulfone
metabolites
are
the
residues
of
concern
for
both
tolerance
reassessment
and
risk
assessment
purposes.
Currently
established
tolerances
for
aldicarb
and
its
metabolites
range
from
0.002
ppm
in
milk
to
1
ppm
in
potatoes.
The
metabolic
breakdown
and
nature
of
aldicarb
residues
in
plants
and
livestock
are
adequately
Page
27
of
51
understood,
based
on
metabolism
studies
conducted
in
lemons,
cotton,
peanuts,
potatoes,
and
sugar
beets,
and
in
ruminants
and
poultry.
These
studies
have
shown
that
following
soil
application,
aldicarb
is
readily
taken
up
through
root
systems
and
translocated
throughout
the
plant.
Aldicarb
is
oxidized
to
form
the
cholinesterase­
inhibiting
metabolites
aldicarb
sulfoxide
and
aldicarb
sulfone.
Further
hydrolysis
of
the
cholinesterase­
inhibiting
parent
and
metabolites
yields
the
(
less
toxic)
oxime,
acid,
nitrile
and
alcohol
derivatives
of
the
carbamate
metabolites.
The
metabolic
pathway
in
livestock
is
similar
to
that
observed
in
plants;
in
addition,
the
tentative
identification
of
radiolabeled
fatty
acids
and
glycerol
in
eggs,
and
the
significant
levels
of
dispersed
radioactivity
in
the
chromatograms
of
tissue
extracts,
suggest
incorporation
of
degraded
aldicarb
into
the
biochemical
pathway.

Adequate
data
collection
and
enforcement
analytical
methods
are
available
for
aldicarb
and
its
metabolites.
The
enforcement
method
involves
oxidation
of
aldicarb
and
aldicarb
sulfoxide
to
aldicarb
sulfone;
total
residues
are
quantified
as
the
sulfone
(
Pesticide
Analytical
Manual,
Volume
II,
Method
II)
using
gas­
liquid
chromatography
with
flame
photometric
detection
in
the
sulfur
mode
(
GLC/
FPD).
Data
collection
methods
that
have
been
used
to
generate
residue
data
in
certain
commodities
(
e.
g.,
potatoes
and
citrus)
separately
quantify
aldicarb
and
its
metabolites
using
high
performance
liquid
chromatography
(
HPLC).

Aldicarb
and
aldicarb
sulfone
residues
are
completely
recovered
(>
80%)
using
multiresidue
method
PAM
Volume
I
Section
302
(
Luke
method;
Protocol
D)
and
Section
401
(
method
for
N­
methylcarbamates).
Aldicarb
sulfoxide
residues
are
also
completely
recovered
using
multiresidue
method
Section
302,
but
are
only
partially
recovered
(
50­
80%)
using
Section
401.

In
most
raw
agricultural
commodities
(
RACs),
aldicarb
and
metabolite
residues
are
expected
to
be
low
or
nondetectable;
however,
in
the
past,
higher
residues
have
been
known
to
occur
in
individual
citrus
(
orange
and
grapefruit),
potatoes
and
sweet
potatoes.
In
general,
the
parent,
aldicarb
per
se
is
not
detected
in
plants;
residues
of
aldicarb
sulfoxide
tend
to
be
detected
more
often
and
at
higher
levels
than
aldicarb
sulfone.

Residues
of
concern
are
not
likely
to
be
detected
in
livestock
tissues,
milk
and
eggs,
and
HED
has
previously
recommended
against
establishing
tolerances
for
residues
in
poultry
commodities.
HED
has
recommended
revocation
of
existing
tolerances
for
aldicarb
residues
in
livestock
commodities.
Aldicarb
and
metabolite
residues
generally
do
not
concentrate
during
processing,
with
the
exception
of
certain
dried
commodities.
Since
aldicarb
is
a
systemic
pesticide,
food
preparation
activities
such
as
washing
and
peeling
are
not
likely
to
reduce
residues;
however,
special
studies
in
potatoes
have
shown
a
reduction
in
residues
during
baking
(
oven)
and
boiling.
There
is
a
potential
for
uptake
of
residues
in
rotational
crops;
therefore,
rotational
crop
tolerances
or
adequate
plantback
intervals
have
been
recommended.

Extensive
monitoring
data
for
aldicarb
have
been
generated
in
composite
samples
of
numerous
commodities
and
in
multiple
years
by
the
USDA
Pesticide
Data
Program
(
PDP)
and
the
FDA
Surveillance
Monitoring
Program.
Monitoring
data
reflect
residues
in
commodities
closer
to
the
point
of
consumption
(
i.
e.,
"
dinner
plate")
rather
than
the
maximum
residues
generated
in
field
trials,
and
can
be
used
in
dietary
exposure
analyses
to
determine
a
more
realistic
estimate
of
dietary
exposure
and
risk.
In
addition
to
the
composite
commodity
samples
routinely
analyzed
by
USDA,
PDP
conducted
a
special
study
on
aldicarb
in
potatoes
during
1997,
which
Page
28
of
51
was
designed
to
provide
a
comparison
between
a
composite
residue
value
and
the
distribution
of
residues
within
that
sample
on
a
single­
serving
basis.
The
study
included
measurements
of
aldicarb
residues
in
composite
samples
and
individual
potatoes
within
those
composites.
The
Carbamate
Task
Force
(
CTF)
submitted
a
1999
market
basket
survey
which
included
single
oranges
collected
in
grocery
stores
and
analyzed
for
aldicarb
and
metabolite
residues.

In
addition
to
the
available
monitoring
data,
extensive
field
trials
have
been
conducted
in
which
total
and
individual
residues
have
been
quantified
in
both
composite
and
individual
citrus
fruits
and
potato
tubers,
including
sweet
potatoes.
Many
of
these
data
are
considered
to
be
"
farm
gate"
monitoring
data;
they
do
not
reflect
the
worst­
case
conditions
of
field
trials,
but
are
not
as
close
to
the
point
of
consumption
as
true
monitoring
data.
In
the
"
farm
gate"
monitoring
data
generated
by
the
registrant
and
various
food
processors,
most
of
the
analyzed
commodities
were
known
to
have
been
treated.

Proposed
amended
label
requests
would
allow
the
establishment
of
a
citrus
crop
group
tolerance;
a
shorter
pre­
harvest
interval
(
PHI,
from
150
to
120
days)
on
potatoes
grown
in
the
Pacific
Northwest;
use
on
potatoes
in
six
Midwestern
states;
and
an
import
tolerance
for
residues
in
bananas.
All
of
the
proposed
label
amendments
are
supported
by
adequate
residue
data,
which
indicate
there
would
be
no
need
to
increase
or
amend
associated
tolerances.
The
proposed
use
on
bananas
involves
water­
soluble
packaging
and
specialized
application
equipment
designed
to
minimize
applicator
exposures.
Multiple
years
of
field
trial
data
for
bananas
have
shown
there
would
be
no
detectable
residues
in
individual
bananas,
or
in
whole
bananas,
peel,
pulp,
puree
or
chips.
In
conjunction
with
the
preliminary
risk
assessment,
HED
has
been
requested
to
estimate
dietary
exposure
associated
with
the
proposed
label
amendments
and
the
import
tolerance.

4.2.2
Dietary
Exposure
An
aldicarb
acute
dietary
exposure
assessment
was
conducted
using
the
Dietary
Exposure
Evaluation
Model
(
DEEM­
FCID
 
)
software
Version
2.0,
which
incorporates
consumption
data
from
USDA's
Continuing
Surveys
of
Food
Intake
by
Individuals
(
CSFII),
1994­
96,
98.
For
risk
assessment
purposes
the
risk
estimates
were
based
on
the
rat
red
blood
cell
cholinesterase
depression
endpoint.
Results
based
on
rat
brain
cholinesterase
depression
and
the
endpoint
defined
in
humans
are
provided
for
characterization
purposes.

The
aldicarb
acute
dietary
exposure
assessments
were
highly
refined,
incorporating
monitoring
and
market
basket
survey
data
from
the
USDA/
PDP
(
potatoes)
and
the
CTF
(
oranges).
These
two
data
sets
were
used
to
assess
exposure
from
all
potato
and
sweet
potato
food
forms,
as
well
as
all
citrus
commodities
and
food
forms
(
orange,
grapefruit,
lemon
and
lime).

In
the
1997
PDP
special
survey,
aldicarb
and
its
metabolites
were
analyzed
in
342
composite
potato
samples
collected
from
states
where
aldicarb
can
be
applied
(
FL,
ID,
OR
and
WA).
Residues
were
detected
in
20
composite
samples,
and
individual
potato
tubers
(
10
per
composite)
from
16
of
the
composites
with
detects
were
analyzed.
The
Page
29
of
51
highest
combined
residue
in
a
composite
sample
was
0.17
ppm,
which
is
below
the
reassessed
tolerance
of
0.2
ppm.
The
highest
residue
in
an
individual
tuber
was
approximately
0.4
ppm,
or
twice
the
tolerance.
In
the
CTF
market
basket
survey,
aldicarb
and
metabolite
residues
were
measured
in
399
peeled
oranges
collected
from
grocery
stores;
residues
were
detected
in
16
of
the
oranges
sampled.
The
maximum
orange
residue
of
0.03
ppm
is
10
times
lower
than
the
reassessed
tolerance
of
0.3
ppm.
In
both
the
PDP
and
CTF
studies,
detected
residues
were
the
sulfone
and
sulfoxide
metabolites,
but
aldicarb
per
se
was
not
detected.

The
PDP
and
CTF
data
were
considered
the
best
available
data
(
for
potatoes
and
citrus)
for
use
in
the
dietary
exposure
assessments,
since
they
reflect
typical
"
dinner
plate"
exposures,
and
would
not
tend
to
significantly
overestimate
dietary
exposure.
For
all
other
commodities,
field
trial
data
were
used
in
the
assessment,
but
residues
were
either
very
low
or
nondetectable
(
soybeans,
cottonseed,
peanuts,
dry
beans
and
coffee).
Sugarbeet
and
sugarcane
were
excluded
from
the
assessments,
since
aldicarb
residues
would
not
be
expected
in
the
processed
commodities
as
consumed;
the
existing
tolerance
for
sorghum
was
used
in
the
assessment,
but
did
not
contribute
to
estimated
dietary
exposure
due
to
the
low
%
CT,
the
low
tolerance,
and
the
low
consumption.

The
most
recent
aldicarb
use
data
and
%
CT
estimates
provided
in
the
12/
99
and
5/
00
Quantitative
Usage
Analyses
(
QUA)
were
incorporated
into
the
preliminary
dietary
exposure
analyses.
Differences
in
%
CT
estimates
for
fresh
vs.
processed
potatoes,
oranges
and
grapefruit
were
included
in
the
dietary
exposure
analyses.
In
addition,
extensive
processing/
cooking
data,
generally
indicating
reduction
of
residues
through
boiling
and
juicing,
were
incorporated
into
the
assessment.
For
potatoes,
processing
factors
of
0.3X,
0.6X
and
0.5X
were
used
for
dried,
fried
and
boiled/
cooked
potatoes,
respectively.
Since
aldicarb
is
systemic,
typical
home
preparation
practices
such
as
washing
and
peeling
would
not
significantly
reduce
residues.

4.2.2.1
Acute
Dietary
Exposure
In
accordance
with
current
HED
policy,
when
acute
dietary
exposure
is
determined
using
the
full
distribution
of
available
residue
data
and
includes
estimates
of
%
CT,
percapita
risk
is
reported
at
the
99.9th
percentile
of
exposure.
If
risks
exceed
HED's
level
of
concern
at
the
99.9th
percentile,
and
for
purposes
of
risk
characterization,
additional
analyses
may
be
conducted
to
determine
which
crops
or
commodities
are
significant
risk
contributors.
Aldicarb
acute
dietary
exposure
assessments
were
conducted
for
the
general
US
population,
all
infants
<
1
year;
children
1­
2
years;
children
3­
5
years,
children
6­
12
years;
youth
13­
19,
Adults
20­
49,
adults
50+,
and
females
13­
49
years;
males
13­
19
years;
males
20+
years;
and
seniors
55+
years.

Tables
8
and
9
present
comparative
risk
estimates
calculated
based
on
rat
RBC
ChEI,
rat
brain
ChEI
and
Human
RBC
ChEI.
Estimated
acute
dietary
exposure
and
risk
exceed
HED's
level
of
concern
[
i.
e.,
>
100
%
aPAD]
for
children
1­
2
years
and
children
3­
5
years
old.
The
estimated
dietary
exposure
and
risk
for
these
two
population
subgroups
at
the
99.9th
percentile
exposure
using
the
rat
RBC
ChEI
endpoint
was
0.000797
mg/
kg/
day,
or
159%
aPAD
and
0.000643
mg/
kg/
day
or
129%
aPAD,
Page
30
of
51
respectively.
For
the
general
US
population,
estimated
dietary
exposure
was
0.000358
mg/
kg/
day,
or
72%
aPAD.
Estimated
exposure
and
risk
were
below
HED's
level
of
concern
(
i.
e.,
<
100
%
aPAD)
at
the
99.8th
percentile
for
both
children
1­
2
years
old
and
children
3­
5
years
old.
If
the
PAD
is
based
on
the
rat
brain
ChEI
or
human
RBC
ChEI
endpoint,
risks
estimates
are
above
HED's
level
of
concern
for
children
1­
2
years
old
(
106%
ad
122%,
respectively).

Because
estimated
dietary
exposure
was
above
HED's
level
of
concern,
an
analysis
was
conducted
to
determine
the
foods
or
food
forms
which
contribute
the
most
to
the
exposure
estimates.
For
all
population
subgroups,
residues
in
potatoes
were
the
most
significant
source
of
dietary
exposure.

Sensitivity
analyses
were
conducted
to
determine
if
assumptions
for
nondetectable
residues
overestimated
exposures.
These
analyses
consisted
of
(
1)
assuming
aldicarb
per
se
residues
were
0
ppm;
and
(
2)
assuming
nondetect
residues
in
citrus
monitoring
samples
were
true
zeroes.
The
assumption
of
zero
residues
for
aldicarb
per
se
had
a
greater
impact
on
the
estimated
exposure
than
the
assumption
of
zero
residue
values
for
citrus
nondetects.
However,
the
sensitivity
analyses
did
not
significantly
reduce
the
estimated
exposure
and
risk
for
any
of
the
population
subgroups
(
Table
9b).
These
analyses
indicate
that
actual
detected
residues
from
monitoring
data
were
the
source
of
the
exposure
and
risk,
and
not
assumed
residues
for
nondetects.
For
the
general
US
population,
assuming
aldicarb
residues
of
0
ppm
and
zero
residues
for
nondetects
in
citrus,
the
estimated
exposure
was
reduced
to
70
%
aPAD;
for
children
1­
2
years
old,
the
estimated
exposure
was
reduced
to
154
%
aPAD.

Since
residues
in
citrus
and
potatoes
were
identified
as
significant
contributors
to
estimated
dietary
exposure,
analyses
were
conducted
in
which
citrus
and
potato
commodities
were
separately
omitted
from
the
exposure
assessment.
When
citrus
commodities
were
excluded,
estimated
exposure
for
children
1­
2
years
old
was
151
%
of
the
aPAD;
exposures
for
children
3­
5
years
old
were
119
%
of
the
aPAD,
while
exposures
for
the
general
US
population
and
all
other
population
subgroups
ranged
from
54­
90%
of
the
aPAD.
When
potato
commodities
were
excluded,
the
highest
estimated
exposure
was
for
children
1­
2,
at
0.000199
mg/
kg/
day,
or
40%
of
the
aPAD;
estimated
exposures
for
all
other
population
subgroups
ranged
from
5
to
32%
of
the
aPAD
(
see
Table
9b).

Proposed
amended
label
requests
would
allow
the
establishment
of
a
citrus
crop
group
tolerance;
a
shorter
pre­
harvest
interval
(
PHI,
from
150
to
120
days)
on
potatoes
grown
in
the
Pacific
Northwest;
use
on
potatoes
in
six
Midwestern
states;
and
an
import
tolerance
for
residues
in
bananas.
Acute
dietary
exposure
analyses
were
conducted
to
determine
the
potential
increased
incremental
exposure
associated
with
each
of
these
proposed
registration
actions,
even
though
exposures
estimated
for
the
existing
uses
already
exceed
HED's
level
of
concern.
These
additional
assessments
indicate
there
would
be
little
or
no
increased
dietary
exposure
and
risk
associated
with
the
establishment
of
a
citrus
crop
group
tolerance
or
a
proposed
import
tolerance
in
bananas.
However,
increased
dietary
exposure
would
be
incurred
if
the
two
label
amendments
for
potatoes
were
approved.
Inclusion
of
both
potato
label
amendments
Page
31
of
51
resulted
in
an
estimated
risk
of
216%
of
the
aPAD
for
children
1­
2
years
old.
Based
on
individual
assessments
for
the
two
label
amendments,
the
proposed
shorter
PHI
results
in
a
greater
incremental
increase
in
the
estimated
exposure
than
the
use
on
potatoes
in
six
additional
Midwestern
states.
More
detailed
information
about
these
assessements
can
be
found
in
the
document
titled
Aldicarb
Revised
Anticipated
Residues
and
Dietary
Exposure
Analyses
for
the
HED
Human
Health
Risk
Assessment
dated
April
28,
2006.
The
results
of
the
acute
dietary
exposure
assessments
are
shown
in
Tables
8
and
9.

4.2.2.2
Chronic
Dietary
A
chronic
assessment
was
not
conducted
because
the
toxicity
database
for
aldicarb
indicates
that
the
magnitude
of
ChEI
does
not
increase
with
continued
exposure,
due
to
the
reversibility
of
ChEI
(
generally
within
24
hours).
The
longer­
term
exposures
could
be
considered
as
a
series
of
acute
exposures.
Page
32
of
51
Table
8.
Aldicarb
Acute
(
Food
Only)
Dietary
Exposure
and
Risk
(
99.9th
%
ile)
 
Existing
Registrations
Population
Exposure
(
mg/
kg/
day)
Rat
(
RBC
ChEI)
%
PAD
Rat
(
Brain
ChEI)
%
PAD
Human
(
RBC
ChEI)
%
PAD
U.
S.
Pop
0.000358
72
48
55
All
Infants
0.000463
93
62
71
Children
1­
2
years
0.000797
159
106
123
Children
3­
5
years
0.000643
129
86
99
Children
6­
12
years
0.000457
91
61
70
Youth
13­
19
0.000312
62
42
48
Adults
20­
49
yrs:
0.000298
60
40
46
Adults
50+
0.000320
64
43
49
Females13­
49
0.000282
56
38
43
Population
Adjusted
Dose
(
PAD)
=
0.0005
mg/
kg/
day
Rat
(
RBC
CheI)
0.00075
mg/
kg/
day
Rat
(
Brain
CheI)
0.00065
mg/
kg/
day
Human
(
RBC
CheI)

Table
9a.
Sensitivity
Analysis
­
Aldicarb
Acute
Dietary
Exposure
and
Risk
(
99.9th
%
ile)
 
(
Aldicarb
=
0;
citrus
nondetects
=
0)

Population
Exposure
(
mg/
kg/
day)
Rat
(
RBC
ChEI)
%
PAD
Rat
(
Brain
ChEI)
%
PAD
Human
(
RBC
ChEI)
%
PAD
U.
S.
Pop
0.000348
70
46
54
All
Infants
0.000444
89
59
68
Children
1­
2
years
0.000772
154
103
119
Children
3­
5
years
0.000623
125
83
96
Children
6­
12
years
0.000443
89
59
68
Youth
13­
19
0.000301
60
40
46
Adults
20­
49
yrs:
0.000290
58
39
45
Adults
50+
0.000314
63
42
48
Females13­
49
0.000274
55
37
42
1.
In
citrus
and
potato
commodities,
aldicarb
per
se
residues
were
assumed
to
be
0
ppm;
in
citrus
commodities,
2.
All
nondetectable
residues
were
assumed
to
be
0
ppm.
Population
Adjusted
Dose
(
PAD)
=
0.0005
mg/
kg/
day
Rat
(
RBC
CheI)
0.00075
mg/
kg/
day
Rat
(
Brain
CheI)
0.00065
mg/
kg/
day
Human
(
RBC
CheI)
Page
33
of
51
Table
9b.
Aldicarb
Sensitivity
Analysis
No
citrus
No
potatoes
Population
Exposure
Rat
(
RBC
ChEI)
Rat(
Brain
ChEI)
Human
(
RBC
ChEI)
Exposure
Rat
(
RBC
ChEI)
Rat(
Brain
ChEI)
Human
(
RBC
ChEI)
U.
S.
Pop
0.000337
67
45
52
0.000063
13
8.4
9.7
All
Infants
0.000433
87
58
67
0.000025
5.0
3.4
3.9
Children
1­
2
years
0.000755
151
101
116
0.000199
40
26
31
Children
3­
5
years
0.000597
119
80
92
0.000162
32
22
25
Children
6­
12
years
0.000452
90
60
70
0.000101
20
13
16
Youth
13­
19
0.000300
60
40
46
0.000067
13
9.0
10
Adults
20­
49
yrs:
0.000283
57
38
44
0.000050
10
6.7
7.7
Adults
50+
0.000307
61
41
47
0.000052
10
6.9
7.9
Females13­
49
0.000270
54
36
42
0.000055
11
7.3
8.4
Population
Adjusted
Dose
(
PAD)
=
0.0005
mg/
kg/
day
Rat
(
RBC
CheI)
0.00075
mg/
kg/
day
Rat
(
Brain
CheI)
0.00065
mg/
kg/
day
Human
(
RBC
CheI)
Page
34
of
51
4.3
Water
Exposure/
Risk
Pathway
In
accordance
with
the
requirements
of
FQPA,
HED
human
health
risk
assessments
must
consider
the
potential
for
exposure
to
pesticides
in
drinking
water.
The
Environmental
Fate
and
Effects
Division
(
EFED/
OPP)
has
completed
a
drinking
water
assessment
for
the
aldicarb
RED
[
J.
Angier,
5/
10/
05,
D316754].
The
potential
for
aldicarb
to
reach
and
contaminate
ground
water
was
discovered
in
1979,
when
high
residues
were
detected
in
ground
water
on
Long
Island,
NY.
Concerns
for
aldicarb
in
ground
water
prompted
the
Agency
to
place
aldicarb
in
Special
Review
status.

4.3.1
Environmental
Fate
Properties
The
environmental
fate
database
for
aldicarb
and
its
primary
degradates,
aldicarb
sulfoxide
and
aldicarb
sulfone,
is
incomplete.
However,
sufficient
information
is
available
to
characterize
the
potential
for
aldicarb
and
its
degradates
to
reach
and
persist
in
ground
and
surface
water
sources
of
drinking
water.

Total
aldicarb
residues
(
i.
e.,
aldicarb
plus
the
sulfoxide
and
sulfone
transformation
products)
are
persistent
and
mobile
in
most
soil
types.
The
environmental
profile
is
similar
to
that
observed
in
plants,
which
consists
of
rapid
oxidation
of
the
parent
aldicarb
to
aldicarb
sulfoxide
and
sulfone,
followed
by
breakdown
(
largely
through
hydrolysis)
to
the
relatively
non­
toxic
non­
carbamate
residues.
The
sulfoxide
and
sulfone
are
more
soluble
in
water
than
the
parent,
aldicarb.

Aldicarb
degradates
readily
leach
to
ground
water
when
aldicarb
is
applied
in
areas
with
permeable
(
sandy)
soil,
significant
rainfall,
and
shallow
water
tables.
The
vast
amount
of
ground
water
monitoring
data
demonstrate
that
once
aldicarb
residues
reach
ground
water,
they
degrade
very
slowly.
Aldicarb
residues
have
recently
been
detected
in
ground
water
in
areas
where
aldicarb
usage
has
been
prohibited
for
at
least
15
years.
Temperature
is
a
significant
factor
in
controlling
aldicarb
degradation
in
ground
water,
and
increased
persistence
is
observed
in
cooler
northern
climates.
However,
most
community
ground
water
supplies
are
from
deeper,
confined
aquifers
that
would
not
likely
be
contaminated
with
aldicarb
residues.
Therefore,
people
most
likely
to
be
exposed
to
aldicarb
residues
in
drinking
water
are
those
who
have
private
(
domestic)
wells
in
vulnerable
aldicarb
use
areas.

Surface
water
monitoring
data
for
aldicarb
and
its
metabolites
are
limited,
especially
when
compared
with
the
quantity
of
ground
water
monitoring
data.
In
non­
targeted
monitoring,
samples
collected
from
major
rivers
or
water
bodies
have
generally
shown
low
or
nondetectable
aldicarb
residues.
However,
some
studies
targeted
to
aldicarb
use
areas
have
shown
some
aldicarb
detects
in
low
order
streams
and
surface
waters.
EPA's
Office
of
Water
(
OW)
reported
no
detects
of
aldicarb
in
17,000
samples
of
raw
or
finished
drinking
water.
In
one
published
study
conducted
in
FL,
aldicarb
residues
were
detected
in
raw,
but
not
finished,
drinking
water;
however,
the
Agency
does
not
consider
this
one
study
to
be
representative
of
surface
water
contamination
with
aldicarb
residues,
nor
of
the
potential
for
all
water
treatment
plants
to
remove
such
residues.

EPA
promulgated
a
final
National
Primary
Drinking
Water
Regulation
for
aldicarb,
aldicarb
sulfoxide,
and
aldicarb
sulfone
on
July
1,
1991.
EPA
set
the
maximum
Page
35
of
51
contaminant
level
goal
(
MCLG,
a
non­
enforceable
health
goal
that
is
used
as
the
target
for
enforceable
Maximum
Contaminant
Levels,
or
MCLs)
at
0.001
part
per
billion
(
ppb)
and
MCLs
of
0.003
ppb
for
aldicarb,
0.004
ppb
for
aldicarb
sulfoxide,
and
0.002
ppb
for
aldicarb
sulfone.
In
response
to
an
administrative
petition
from
the
manufacturer
and
primary
data­
doer,
the
Agency
issued
an
administrative
stay
of
the
effective
date
of
the
MCLs;
i.
e.,
the
MCLs
never
became
effective.

The
Agency
issued
an
updated
drinking
water
health
advisory
in
1995.
Health
advisories
serve
as
informal
technical
guidance
to
assist
officials
responsible
for
protecting
public
health
(
e.
g.,
spills
or
contamination)
but
are
not
enforceable
federal
standards.
The
portion
of
an
individual's
total
exposure
that
is
considered
protective
of
adverse
health
effects
over
a
lifetime
of
exposure
for
aldicarb,
aldicarb
sulfoxide,
and
aldicarb
sulfone,
and
total
aldicarb
residues
were
each
set
at
7
ppb.

4.3.2
Estimated
Environmental
Concentrations
(
EECs)/
Monitoring
Data
Since
surface
water
monitoring
data
for
aldicarb
were
too
limited
to
be
used
quantitatively
in
the
drinking
water
exposure
assessment,
EFED
used
Tier­
II
modeling
to
generate
estimated
environmental
concentrations
(
EECs)
in
surface
water.
Specifically,
the
Pesticide
Root
Zone
Model
and
Exposure
Analysis
Model
System
(
PRZM/
EXAMS)
Index
Reservoir
was
used
to
generate
surface
water
EECs
for
drinking
water.
The
model
is
used
by
OPP
to
estimate
pesticide
concentrations
that
may
be
in
surface
water
due
to
pesticide
use
and
runoff.
The
PRZM/
EXAMS
estimates
of
potential
pesticide
levels
in
surface
water
incorporate
pesticide­
specific
properties,
simulation
of
multiple
years
to
reflect
climatic
variations,
and
modeling
on
a
crop­
specific
basis.

A
Tier
II
EEC
for
a
particular
crop
or
use
is
based
on
a
single
site
that
represents
a
high
exposure
scenario
for
the
crop
or
use.
Weather
and
agricultural
practices
are
simulated
at
the
site
for
36
years
to
estimate
the
probability
of
exceeding
a
given
concentration
(
maximum
concentration
or
average
concentration)
in
a
single
year.
Maximum
EECs
are
calculated
so
that
there
is
a
10%
probability
that
the
maximum
concentration
in
a
given
year
will
exceed
the
EEC
at
the
site;
this
can
also
be
expressed
as
an
expectation
that
water
concentrations
will
exceed
EECs
once
every
10
years.

A
distribution
of
estimates
of
possible
concentrations
in
drinking
water
were
used
in
the
dietary
assessment.
Approximately
11000
values
were
generated
based
on
maximum
aldicarb
use
patterns
in/
on
Florida
citrus,
Idaho
potatoes,
and
Mississippi
cotton.
The
values
were
adjusted
for
percent
crop
area
(
PCA)
using
a
factor
of
0.87.
These
values
represent
the
complete
daily
36
year
PRZM
EXAMS
output
distribution
and
are
considered
somewhat
conservative,
but
are
within
the
range
of
aldicarb
detects
in
targeted
surface
water
monitoring
data..
A
RDF
file
was
created
using
these
values
for
the
two
commodities
"
Water,
direct,
all
sources"
and
"
Water,
indirect,
all
sources"
in
the
residue
file
editor
for
DEEM­
FCID.
The
range
of
the
concentrations
are
shown
in
Table
10.
Page
36
of
51
Table
10.
Acute
and
Chronic
Surface
Water
EECs
for
Dietary
Exposure
Crop/
Location
Acute
Concentration
(
ppb)

Mississippi
Cotton
0
­
38.6
Idaho
Potato
0
­
5.8
Florida
Citrus
0
­
13.1
Ground
water
monitoring
for
aldicarb
and
metabolite
residues
has
been
extensive
over
the
last
two
decades.
Over
47,000
individual
samples
were
collected
and
analyzed
during
this
time.
Monitoring
data
sources
include
the
registrant,
Bayer
(
formerly
Aventis
CropScience,
formerly
RPAC),
STORET,
the
U.
S.
Geological
Survey
(
USGS),
state
and
local
governments,
and
university
researchers.
[
The
STOrage
and
RETrieval
(
STORET)
system
is
a
database
maintained
by
EPA
which
contains
information
on
water
monitoring
data
including
where
and
when
the
sample
was
taken,
and
the
name
of
the
organization
that
sponsored
the
monitoring.]
The
ground
water
monitoring
data
are
discussed
in
detail
and
summarized
in
the
EFED
RED
chapter.

Although
the
ground
water
data
are
extensive,
they
are
not
ideal
for
direct
use
in
probabilistic
exposure
models
for
a
variety
of
reasons.
In
most
areas
where
there
has
been
ground
water
contamination
from
aldicarb,
steps
have
been
taken
to
mitigate
exposures,
either
through
filtering
or
through
use
of
alternative
sources
of
drinking
water.
Ground
water
sampling
has
also
varied
in
frequency
and
scope
over
the
years,
generally
declining
during
the
last
10
to
12
years.
Some
of
the
monitoring
data
do
not
reflect
current
use
areas
and
rates,
and
do
not
reflect
present
conditions.
[
Current
label
restrictions
prohibit
aldicarb
application
in
areas
where
there
have
been
historical
concerns
for
ground
water
contamination
(
i.
e.,
Del
Norte
and
Humboldt
counties
in
CA,
Curry
County
in
OR,
and
Nassau
and
Suffolk
Counties
in
NY).
Aldicarb
is
not
registered
for
use
in
Northeastern
states.
However,
regions
presenting
soil/
stratigraphic/
hydrologic
attributes
similar
to
these
historical
problem
areas
should
be
considered
potentially
vulnerable
to
groundwater
contamination].
Overall,
the
extent
of
ground
water
contamination
today
may
be
less
than
in
the
past,
but
it
is
also
not
well­
characterized.

For
the
purpose
of
the
drinking
water
assessment,
ground
water
concentrations
have
been
presented
on
a
regional
basis.
Eight
distinct
regions
were
selected
based
on
broad
similarity
in
aldicarb
usage,
crop
type
or
soil
conditions.
The
monitoring
data
from
each
region
were
examined,
and
a
single
maximum
sample
result
was
chosen
to
represent
ground
water
concentrations
within
the
entire
region.
For
each
region,
the
sample
chosen
was
detected
the
within
the
last
5
to
10
years
(
i.
e.,
higher
residue
values
that
may
have
resulted
from
historical
use
of
aldicarb
in
vulnerable
areas
were
excluded).
The
aldicarb
water
residue
values
chosen
for
the
drinking
water
assessment
are
considered
to
be
somewhat
conservative,
because
they
reflect
exposures
to
people
who
are
most
highly
exposed
in
each
region.
The
population
potentially
exposed
at
these
levels
consists
of
individuals
who
obtain
drinking
water
from
private
wells
in
areas
with
vulnerable
soils,
or
that
may
be
contaminated
from
past
agricultural
applications
of
aldicarb.
A
summary
of
the
ground
water
concentrations
for
use
in
the
drinking
water
exposure
assessment
is
presented
in
Table
11.
Page
37
of
51
Table
11.
Suggested
Aldicarb
Ground
Water
Concentrations
for
Use
in
the
Drinking
Water
Assessment.

Region1
Location
and
Year
of
Detection
Aldicarb
Concentration
(
ppb)
Data
Source
Rationale
for
Selection
A
ID;
Caribou
Co.,
1992
2.1
State
of
ID
Max.
conc.
since
1990
B
CA;
Solano
Co.,
1997
6.4
State
of
CA
Max.
conc.
since
1997;
most
recent
detect
in
region.
C
WY;
Washakie
Co.,
1992
9.7
Registrant
Max.
conc.
since
1992;
second
most
recent
detect
in
region
D
N/
A
0.0
N/
A
No
aldicarb
detections
reported
from
this
region.
E
WI;
Langlade
Co.,
1992
23.0
Registrant
Max.
conc.
since
1992.
Very
little
data
available
after
1994;
however,
2
detects
above
10
ppb
in
1997.
F
RI;
Newport
Co.,
1994
24.0
State
of
RI
Max.
conc.
since
1994;
fourth
most
recent
detection
in
region.
G
AL,
Baldwin
Co.,
1990
20.0
Registrant
Max.
conc.
since
1990.
No
data
available
after
1993.
H
FL,
Madison
Co.,
1996
9.3
State
of
FL
Max.
conc.
since
1996;
ninth
most
recent
detection
in
region.

1
Regions
are
described
as
follows:
Region
A
=
Pacific
Northwest
(
ID/
OR/
WA);
Region
B
=
CA;
Region
C
=
Central
Plains
and
Western
(
MT,
WY,
NV,
UT,
CO,
KS,
NE,
ND,
SD,
MN,
IA,
MO);
Region
D
=
Southwest
and
Central
Plains
(
AZ,
NM,
TX,
OK);
Region
E
=
Midwest
and
Central
Plains
(
WI,
IL,
IN,
MI,
OH,
WV,
PA,
NJ,
DE,
MD);
Region
F
=
New
England
(
NY,
VT,
NH,
MA,
CT,
RI,
ME);
Region
G
=
Southeast
(
AR,
LA,
MS,
AL,
GA,
TN,
KY,
SC,
NC,
VA,
DC);
Region
H
=
FL.

4.4
Residential
Exposure/
Risk
Pathway
No
aldicarb
products
are
intended
for
sale
to
homeowners
or
for
use
by
professional
applicators
in
residential
environments.
In
addition,
the
potential
for
off­
target
migration
of
aldicarb
during
agricultural
applications
is
minimal,
due
to
the
physical
characteristics
of
the
products
(
all
granular
formulations)
and
the
requirement
for
soil
incorporation
at
treatment.
Therefore,
no
residential
exposure/
risk
assessment
has
been
completed
in
conjunction
with
the
agricultural
uses
for
aldicarb.
However,
an
inhalation
risk
assessment
for
adult
smokers
has
been
completed
since
aldicarb
is
registered
for
use
on
tobacco.

In
assessing
exposure
through
use
of
tobacco,
HED
has
assumed
that
the
greatest
exposure
to
aldicarb
would
come
from
cigarettes.
Further,
HED
has
assumed
that
the
average
U.
S.
smoker
smokes
15
cigarettes
per
day
[
Pierce,
J.
P.,
et
al.
1989.
Tobacco
Use
in
1986
­
Methods
and
Basic
Tabulations
from
Adult
Use
of
Tobacco
Survey.
U.
S.
Dept.
of
Health
and
Human
Services
Publication
Number
OM90­
2004.
Office
on
Smoking
and
Health,
Rockville,
Maryland.].

Residue
data
submitted
to
support
aldicarb
use
on
tobacco
were
reviewed
in
the
Residue
Chemistry
Chapter
of
the
Aldicarb
Reg.
Std.
(
11/
18/
83).
These
data
are
considered
Page
38
of
51
adequate
for
the
purpose
of
assessing
human
exposure
to
aldicarb
residues
in
cigarette
smoke.

In
a
greenhouse
study,
[
14C]
aldicarb
was
applied
close
to
the
1X
rate,
and
residues
were
measured
in
green
leaves,
flue­
cured
leaves,
and
in
smoke.
Residues
in
smoke
were
0.5
ppm,
consisting
of
aldicarb
sulfone
(
0.3
ppm)
and
aldicarb
sulfoxide
(
0.2
ppm).
Total
[
14C]
aldicarb
residues
in
leaves
from
the
greenhouse
study
were
higher
than
those
reported
in
a
field
study.
Smoke
residues
were
not
determined
using
leaves
from
the
field
study.
Therefore,
for
the
purpose
of
this
exposure
assessment,
aldicarb
residues
in
tobacco
smoke
were
assumed
to
be
0.5
ppm;
this
is
considered
to
be
an
overestimate
of
potential
residues
in
smoke,
based
on
the
higher
residues
in
leaves
from
the
greenhouse
study.

In
assessing
exposure
to
aldicarb
from
tobacco,
HED
has
assumed
that
100%
of
the
aldicarb
inhaled
in
the
smoke
is
absorbed
(
i.
e.,
that
none
of
the
residue
is
exhaled
along
with
the
smoke).
This
results
in
an
overestimate
of
actual
likely
exposure.
Assuming
a
smoke
residue
level
of
0.5
ppm,
a
smoking
frequency
of
15
cigarettes
per
day,
and
assuming
an
average
body
weight
of
70
kg,
HED
estimates
that
exposure
to
aldicarb
will
not
exceed
0.000107
mg/
kg/
day
for
males
[
0.5
:
g/
g
cigarette
H
1
g/
cigarette
H
15
cigarettes/
day
H
1
mg/
1000:
g
)
70
kg
body
weight
=
0.000107
mg/
kg/
day]
and
0.000125
mg/
kg/
day
for
females
(
60
kg
body
weight).

The
Margin
of
Exposure
(
MOE)
is
a
measure
of
the
estimated
exposure
with
respect
to
the
Agency's
level
of
concern,
usually
the
NOAEL.
The
MOE
is
expressed
as
a
ratio
of
the
NOAEL
(
or
LOAEL)
to
the
estimated
exposure;
the
higher
the
MOE,
the
lower
the
risk.
The
target
MOE
for
aldicarb
is
20
i.
e.,
10X
(
intraspecies)
and
2X
(
interspecies);
estimated
MOEs
less
than
20
represent
a
risk
concern.
Using
the
inhalation
BMDL10
of
0.05
mg/
kg/
day,
the
short­
term
MOE
for
aldicarb
exposure
from
the
use
of
tobacco
is
estimated
to
be
160
for
females,
and
187
for
males.
These
MOEs
are
greater
than
the
target
MOE
of
20,
indicating
that
exposure
and
risk
from
aldicarb
residues
in
tobacco
are
not
of
concern.
These
estimates
are
considered
to
be
very
conservative
assumptions
with
respect
to
residues
in
tobacco,
and
may
overestimate
exposure
through
this
route.

5.0
AGGREGATE
RISK
ASSESSMENTS
AND
RISK
CHARACTERIZATIONS
In
accordance
with
FQPA,
HED
must
consider
and
aggregate
pesticide
exposures
and
risks
from
three
major
sources:
food,
drinking
water,
and
residential
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.

Since
there
is
no
potential
for
exposure
to
aldicarb
and
metabolites
in
residential
settings,
aggregate
exposure
and
risk
assessments
include
only
dietary
food
and
water
sources
of
exposure,
and
are
limited
to
acute
and
chronic
durations.
Therefore,
the
aggregate
dietary
exposure
(
food
plus
water)
can
be
compared
to
the
acute
PADs
to
determine
the
risk
associated
with
the
estimated
exposures.
Per
Agency
policy,
tobacco
use
is
not
included
in
aggregate
assessments.
Page
39
of
51
5.1
Acute
Aggregate
Risk
Assessment
Typical
acute
aggregate
exposure
and
risk
assessments
include
the
estimated
acute
(
food
only)
exposure
and
acute
surface
water
(
modeled)
and
ground
water
EECs
(
calculated
from
monitoring
data).
For
aldicarb,
estimated
dietary
(
food
only)
exposure
to
aldicarb
for
children
exceeds
the
level
of
concern
for
acute
dietary
exposure.
When
acute
food
exposure
alone
exceeds
the
level
of
concern,
HED
does
not
typically
aggregate
modeled
EECs,
but
states
that
any
additional
exposure
through
drinking
water
would
be
of
concern.
However,
as
a
tool
for
the
risk
managers,
a
"
water
only"
dietary
assessment
was
conducted
assuming
no
exposure
from
food
to
get
an
estimate
of
contribution
of
drinking
water
to
the
dietary
exposure
and
risk.
For
surface
water,
a
distribution
of
concentrations
derived
from
PRZM­
EXAMS
modeling
was
used
in
the
assessment.
For
ground
water,
a
point
estimate
derived
from
monitoring
data
was
used.

If
there
were
no
acute
dietary
food
exposure,
and
all
of
the
allowable
exposure
occurred
through
surface
water
sources
(
i.
e.,
assuming
the
aPAD
of
0.0005
mg/
kg/
day
is
completely
allotted
to
exposure
to
residues
in
water),
HED
would
have
concerns
for
total
aldicarb
residues.
While
aldicarb
is
not
considered
to
have
a
high
potential
to
contaminate
surface
waters,
Tier
II
EECs
calculated
for
all
three
scenarios
are
significantly
greater
than
7
ppb,
which
is
also
the
OW
health
advisory
level.
Acute
drinking
water
exposures
and
risk
estimates
determined
based
on
surface
water
sources
ranged
from
23%
to
458%
aPAD
at
the
99.9th
percentile
of
exposure
based
on
the
rat
RBC
ChEI
endpoint
and
are
shown
in
Table
12.

An
acute
assessment
was
also
conducted
for
ground
water
sources
of
drinking
water,
since
extensive
monitoring
data
are
available.
Acute
risks
estimates
for
the
general
population,
all
infants,
children
1­
2
years
old,
and
females
13­
49
years
old
are
shown
in
Table
13.
The
data
indicate
that
acute
exposure
from
ground
water
sources
of
drinking
water
is
also
of
concern,
with
acute
aggregate
risks
ranging
from
20%
aPAD
to
945%
aPAD.

The
acute
aggregate
risks
(
i.
e.,
drinking
water
+
food)
calculated
based
on
ground
water
monitoring
values
overestimate
risks
for
all
but
those
who
obtain
their
drinking
water
from
wells
in
vulnerable
aldicarb
use
areas.
However,
since
food
only
exposures
exceed
the
aPAD,
HED
is
concerned
about
any
additional
exposure
through
drinking
water,
regardless
of
the
source.
Page
40
of
51
Table.
12.
Aldicarb
Acute
Water
Exposure
and
Risk
for
Select
Population
Subgroups
at
the
95th
%
ile
of
Exposure
[
Based
on
Surface
Water
Concentrations
from
Modeling]
U.
S.
Population
All
infants
Children
1­
2
years
Females
13­
49
Regions
Exposure
%
PAD
Exposure
%
PAD
Exposure
%
PAD
Exposure
%
PAD
Rat
 
RBC
Cotton
0.000025
5.0
0.000078
15
0.000037
7.4
0.000024
5
Potato
0.000006
1.2
0.000015
3.1
0000008
1.6
0.000005
1.1
Citrus
0.000002
0.46
0.000006
1.3
0.000003
0.66
0.000002
0.43
Rat
 
Brain
Cotton
0.000025
3.4
0.000078
10
0.000037
5.0
0.000024
3.2
Potato
0.000006
0.77
0.000015
2.1
0000008
1.1
0.000005
0.72
Citrus
0.000002
0.31
0.000006
0.83
0.000003
0.44
0.000002
0.29
Human
­
RBC
Cotton
0.000025
3.9
0.000078
12
0.000037
5.7
0.000024
3.6
Potato
0.000006
0.89
0.000015
2.4
0000008
1.3
0.000005
0.83
Citrus
0.000002
0.35
0.000006
0.96
0.000003
0.51
0.000002
0.33
1.
EDWCs
were
based
on
the
following
scenarios:
Mississippi
Cotton;
Idaho
Potato;
Florida
Citrus
2.
Generated
using
the
DEEM­
FCID
model
­
Version
2.03
3.
Acute
Aggregate
Risk
=
%
of
the
aPAD=
[(
Total
Exposure/
aPAD
mg/
kg/
day)
x
100]
Table.
13.
Aldicarb
Acute
Water
Exposure
and
Risk
for
Select
Population
Subgroups
at
the
95th
%
ile
of
Exposure.

[
Based
on
Ground
Water
Concentrations
from
Monitoring]

Gen
Population
All
Infants
(<
1
Year)
Children
(
1
­
2
Years)
Females
13­
49
Years
Region1
Aldicarb
Conc.

in
Ground
Water
(
ppb)
Water
Exp.

(
mg/
kg/
day)
2
%
aPAD3
Water
Exp.

(
mg/
kg/
day)
2
%
aPAD3
Water
Exp.

(
mg/
kg/
day)
2
%
aPAD3
Water
Exp.

(
mg/
kg/
day)
2
%
aPAD3
Rat
­
RBC
A
2.1
0.000110
22
0.000414
83
0.000172
34
0.000102
20
B
6.4
0.000334
67
0.001261
252
0.000525
105
0.000312
62
C
9.7
0.000507
101
0.001910
382
0.000795
159
0.000472
94
E
23.0
0.001201
240
0.004530
906
0.001885
377
0.001119
224
F
24.0
0.001254
251
0.004727
945
0.001967
393
0.001168
234
G
20.0
0.001045
139
0.003939
525
0.001639
219
0.000973
130
H
9.3
0.000486
97
0.001832
366
0.000762
152
0.000453
91
Rat
­
Brain
A
2.1
0.000110
15
0.000414
55
0.000172
23
0.000102
14
B
6.4
0.000334
45
0.001261
168
0.000525
70
0.000312
42
C
9.7
0.000507
68
0.001910
255
0.000795
106
0.000472
63
E
23.0
0.001201
160
0.004530
604
0.001885
251
0.001119
149
F
24.0
0.001254
166
0.004727
626
0.001967
261
0.001168
155
G
20.0
0.001045
139
0.003939
525
0.001639
219
0.000973
130
Table.
13.
Aldicarb
Acute
Water
Exposure
and
Risk
for
Select
Population
Subgroups
at
the
95th
%
ile
of
Exposure.

[
Based
on
Ground
Water
Concentrations
from
Monitoring]

Gen
Population
All
Infants
(<
1
Year)
Children
(
1
­
2
Years)
Females
13­
49
Years
Region1
Aldicarb
Conc.

in
Ground
Water
(
ppb)
Water
Exp.

(
mg/
kg/
day)
2
%
aPAD3
Water
Exp.

(
mg/
kg/
day)
2
%
aPAD3
Water
Exp.

(
mg/
kg/
day)
2
%
aPAD3
Water
Exp.

(
mg/
kg/
day)
2
%
aPAD3
H
9.3
0.000486
65
0.001832
244
0.000762
102
0.000453
60
Human
RBC
A
2.1
0.000110
17
0.000414
64
0.000172
26
0.000102
16
B
6.4
0.000334
51
0.001261
194
0.000525
81
0.000312
48
C
9.7
0.000507
78
0.001910
294
0.000795
122
0.000472
73
E
23.0
0.001201
185
0.004530
697
0.001885
290
0.001119
172
F
24.0
0.001254
191
0.004727
722
0.001967
300
0.001168
178
G
20.0
0.001045
161
0.003939
606
0.001639
252
0.000973
150
H
9.3
0.000486
74
0.001832
282
0.000762
117
0.000453
70
1
Regions
are
described
as
follows:
Region
A
=
Pacific
Northwest
(
ID/
OR/
WA);
Region
B
=
CA;
Region
C
=
Central
Plains
and
Western
(
MT,
WY,
NV,
UT,
CO,
KS,
NE,
ND,
SD,

MN,
IA,
MO);
Region
E
=
Midwest
and
Central
Plains
(
WI,
IL,
IN,
MI,
OH,
WV,
PA,
NJ,
DE,
MD);
Region
F
=
New
England
(
NY,
VT,
NH,
MA,
CT,
RI,
ME);
Region
G
=

Southeast
(
AR,
LA,
MS,
AL,
GA,
TN,
KY,
SC,
NC,
VA,
DC);
Region
H
=
FL.
[
There
were
no
detections
in
Region
D,
Southwest
and
Central
Plains
(
AZ,
NM,
TX,
OK)].

2.
Generated
using
the
DEEM­
FCID
model
­
Version
2.03
3
Acute
Aggregate
Risk
=
%
of
the
aPAD=
[(
Total
Exposure/
aPAD
mg/
kg/
day)
x
100]
Page
43
of
51
In
summary,
acute
dietary
food
only
exposure
exceeds
HED's
level
of
concern;
ground
water
monitoring
data
and
surface
water
EECs
from
modeling
indicate
that
potential
exposures
through
drinking
water
in
high
aldicarb
use
areas
are
also
of
concern.
For
surface
and
ground
water
drinking
water
obtained
from
public
and
community
water
systems,
the
potential
effect
of
water
treatment
processes
on
aldicarb
residues
has
not
been
considered;
however,
monitoring
data
indicate
that
these
types
of
drinking
water
sources
are
not
likely
to
be
contaminated
with
aldicarb
residues.

5.1
Chronic
Aggregate
Risk
Assessment
A
chronic
aggregate
assessment
was
not
conducted
because
the
toxicity
database
for
aldicarb
indicates
that
the
magnitude
of
ChEI
does
not
increase
with
continued
exposure,
due
to
the
reversibility
of
ChEI
(
generally
within
8
to
24
hours)
exhibited
by
aldicarb
and
other
carbamate
pesticides.
The
longer­
term
exposures
could
be
considered
as
a
series
of
acute
exposures.

6.0
CUMULATIVE
RISK
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.

The
Agency
has
determination
that
N­
methyl
carbamate
pesticides
should
be
considered
as
a
Common
Mechanism
Group
due
to
their
ability
to
inhibit
acetylcholinesterase.
The
Agency
further
stated
that
this
subgroup
shares
a
common
mechanism
of
toxicity.
A
cumulative
risk
assessment
for
this
Common
Mechanism
Group,
which
includes
aldicarb,
will
be
available
later
this
year.
This
human
health
risk
assessment
is
for
aldicarb,
and
does
not
include
cumulative
exposures
or
risks
from
other
N­
methyl
carbamate
pesticides.

7.0
OCCUPATIONAL
EXPOSURE
The
HED
occupational
exposure
and
risk
assessment
for
aldicarb
is
based
on
a
limited
number
of
occupational
exposure
scenarios,
or
categories
of
exposures,
derived
from
the
uses
described
on
registered
labels.
HED
risk
assessments
typically
consider
several
types
of
potentially
exposed
populations
including:
handlers
who
are
those
involved
in
the
pesticide
application
process
(
e.
g.,
mixer/
loaders
or
applicators)
and
post­
application
workers
or
those
who
can
be
exposed
by
Page
44
of
51
working
in
environments
that
have
been
previously
treated.
The
aldicarb
use
pattern
indicates
that
routine
exposures
are
expected
for
occupational
handlers,
including
loaders
and
applicators.
Due
to
the
application
timing
and
the
requirement
for
soil
incorporation
of
aldicarb
granules,
postapplication
exposures
are
not
generally
expected;
hence,
a
postapplication
exposure
assessment
was
not
conducted.
Section
7.1
presents
the
results
of
the
risk
assessment
for
aldicarb
handlers
while
Section
7.2
describes
the
lack
of
potential
for
post­
application
exposures.

Since
the
toxicological
endpoints
for
aldicarb
dermal
and
inhalation
risk
assessments
were
the
same
(
RBC
cholinesterase
inhibition),
risks
were
expressed
in
terms
of
combined
dermal
and
inhalation
MOEs.
In
addition,
the
same
studies
were
used
to
assess
risks
for
all
pertinent
exposure
durations;
therefore,
risk
estimates
do
not
vary
with
the
duration
of
exposure.

A
summary
of
the
use
pattern
and
formulation
information
for
occupational
risk
assessment
is
provided
in
Table
14.
Page
45
of
51
Table
14.
Aldicarb
Use
Pattern/
Formulation
Information
Relevant
to
Occupational
Exposure
Assessment.

Formulation
Type
Application
Equipment
(
Loader/
Applicator)
Use
Sites
Appl.
Rate
Range
Application
Frequency
Average
Appl.
Rates
Terrestrial
Crops
15G
Solid
broadcast
spreader
Tree
fruit/
Nut
crops
Pecans:
2.6
to
10.1
lb
ai/
A/
season
Citrus:
5
lb
ai/
A
Coffee:
0.11
oz/
tree
[
4.4
lb
ai/
A/
season]
Pecans:
1
or
2x/
season
Citrus:
1x/
Season
Coffee:
2x/
Season
1.4
­
3.8
lb
ai/
A/
year
15G
Solid
broadcast
spreader
Field/
forage
fiber/
small
fruit/
veg.
Beans:
1.1
­
2.1
lb
ai/
A;
Cotton:
0.75
­
4.1
lb
ai/
A;
Peanuts/
Potatoes/
Soybeans/
Sugarcane/
Sweet
potatoes:
3
lb
ai/
A;
Sorghum:
1.1
lb
ai/
A;
Sugar
beets:
2.1­
5
lb
ai/
A
3x/
season
(
max.);
typically
1
or
2x/
season
0.6
­
2.7
lb
ai/
A/
year
15G
Solid
broadcast
spreader
Non­
Food/
Feed
Tobacco:
3
lb
ai/
A
1x/
season
1.6
lb
ai/
A/
year
Ornamental
Crops
10G
Solid
broadcast
spreader
Ornamentals
5
lb
ai/
A
no
data
no
data
7.1
Handler
The
aldicarb
use
pattern
results
in
a
limited
number
of
occupational
handler
scenarios:
(
1)
loading
granules;
and
(
2)
applying
granules
using
a
solid
broadcast
spreader.
Loading
activities
can
involve
both
open
loading
(
i.
e.,
with
typical
bags)
or
the
use
of
closed
Lock­
n­
Load
systems.
Application
activities
can
also
involve
open
or
closed
cab
tractors.
These
scenarios
were
assessed
using
unit
exposures
derived
from
a
chemical­
specific
study
conducted
by
the
registrant
(
MRID
438525­
01)
and
PHED
(
Pesticide
Handlers
Exposure
Database).
The
study
is
chemical­
and
formulation­
specific
in
that
it
used
aldicarb
low­
dust
granules
(
i.
e.,
corn
cob
or
gypsum)
which
are
the
only
commercially
marketed
products.
The
study
quantified
exposures
from
open
loading
and
open
cab
tractor
application
activities.
The
study
is
considered
more
representative
of
exposures
for
these
activities
instead
of
PHED
by
the
Agency
because
PHED
exposure
estimates
are
based
on
the
use
of
more
friable
clay
granules
instead
of
the
low­
friability
aldicarb
products
(
i.
e.,
PHED
exposures
are
based
on
formulations
that
contain
more
dust
than
available
aldicarb
products
which
would
be
expected
to
lead
to
higher
exposures).
Aldicarb
is
also
marketed
in
Lock­
n­
Load
closed
systems
and
can
also
be
applied
using
closed
cab
tractors.
The
study
did
not
quantify
the
exposures
associated
with
the
use
of
these
types
of
engineering
controls
so
PHED
was
used
to
evaluate
these
scenarios
due
to
a
lack
of
chemical­
and
formulation­
specific
data.
[
Note:
Exposure
values
for
both
PHED
and
MRID
438525­
01
are
similar
in
most
instances
and
in
most
cases
are
lower
for
MRID
Page
46
of
51
438525­
01.
It
should
also
be
pointed
out
that
low
friability
granules
can
also
be
considered
an
engineering
control.]

The
following
factors
were
also
used
to
estimate
handler
exposure
and
risk,
and
are
considered
typical
for
HED
handler
assessments:

1.
Exposures
were
assessed
for
an
8­
hour
occupational
workday.
2.
Daily
acres
treated/
day
assumptions
were
80
acres
for
orchard
and
field
crops;
50
acres
for
coffee
plantations;
and
10
acres
for
ornamentals.
3.
Exposures
were
based
on
maximum
application
rates
for
representative
crops.
4.
The
average
body
weight
for
an
adult
handler
is
70
kg.

Estimated
short­
and
intermediate­
term
risks
(
MOEs)
are
presented
in
Table
15
and
were
calculated
based
on
each
of
the
applicable
endpoints
which
have
been
identified.
Results
based
on
the
rat
red
blood
cell
cholinesterase
depression
endpoint
reflect
standard
Agency
policy
for
defining
hazard
inputs
for
risk
assessment
purposes.
Results
based
on
rat
brain
cholinesterase
depression
and
the
endpoint
defined
in
humans
are
provided
for
characterization
purposes.

Risks
were
of
not
concern
for
most
exposure
scenarios
based
on
the
aldicarb
specific
worker
exposure
data
for
loaders
and
applicators
(
MRID
438525­
01),
regardless
of
which
hazard
endpoint
was
considered
(
i.
e.,
rat
RBC,
rat
brain,
or
human).
In
only
a
few
instances
for
loaders
were
risks
identified
that
were
of
concern
based
on
this
study.
Loader
MOEs
based
on
the
rat
RBC
endpoint
(
i.
e.,
MOEs
=
13.6
&
16.4
for
80
acres
at
~
5+
lb
ai/
acre)
and
the
human
endpoint
(
i.
e.,
MOE
=
8.8
for
80
acres
at
6
lb
ai/
acre)
were
just
slightly
below
the
risk
targets
(
i.
e.,
MOEs
=
20
&
10,
respectively).
If
unit
exposures
from
PHED
are
considered,
the
results
are
similar
for
loaders
in
that
risks
were
of
not
concern
for
most
exposure
scenarios
regardless
of
which
hazard
endpoint
was
considered
(
i.
e.,
rat
RBC,
rat
brain,
or
human).
In
only
a
few
instances
for
loaders
based
on
PHED
were
risks
identified
that
were
of
concern.
Loader
MOEs
based
on
the
rat
RBC
endpoint
(
i.
e.,
MOEs
=
14.4
&
17.5
for
80
acres
at
~
5+
lb
ai/
acre)
and
the
human
endpoint
(
i.
e.,
MOE
=
9.4
for
80
acres
at
6
lb
ai/
acre)
were
just
slightly
below
the
risk
targets
(
i.
e.,
MOEs
=
20
&
10,
respectively).
For
applicators
based
on
PHED
data,
the
trend
is
very
different
from
that
observed
with
the
study
data
in
that
risks
were
of
concern
for
all
scenarios
considered
(
i.
e.,
MOEs
range
from
<
1
to
8.2).

In
the
interpretation
of
the
results
of
this
assessment,
several
factors
should
be
considered
including:
Page
47
of
51
°
The
aldicarb
study
(
MRID
43852501)
is
acceptable
for
risk
assessment
purposes
and
exposures
for
open
loading
and
open
cabs
based
on
this
study
better
reflect
aldicarb
exposures
for
these
scenarios
than
PHED
because
it
is
a
chemical­
specific
study
that
mirrors
how
aldicarb
is
packaged,
handled
and
used
in
agriculture.
The
one
issue
that
should
be
considered
is
that
a
number
of
samples
were
reported
as
nondetectable
The
investigators
calculated
exposures
using
non­
detectable
values
in
a
slightly
different
manner
than
would
be
done
by
the
Agency.
The
Agency
investigated
these
differences
and
found
they
did
not
significantly
alter
the
results
of
this
assessment.
Since
closed
loading
and
closed
cabs
were
not
monitored
in
MRID
43852501,
PHED
was
used
to
address
those
scenarios.
It
is
also
not
unexpected
that
in
some
cases
PHED
exposure
estimates
are
higher
than
those
identified
from
the
study
which
is
a
reflection
of
the
limits
of
quantification
achieved
in
each.

°
The
results
of
this
assessment
supercede
those
presented
in
the
previous
risk
assessment
D320376
(
August
11,
2005)
and
the
previous
occupational
and
residential
exposure
chapter
D311821
(
January
11,
2005).
The
scenarios
essentially
remain
the
same
but
the
major
changes
are
that
PHED
estimates
for
engineering
controls
are
now
included
and
the
hazard
inputs
have
been
modified.

°
A
dermal
absorption
factor
of
100
percent
has
been
used
and
if
that
factor
changed,
risks
would
also
change
proportionately.

°
Current
aldicarb
labels
require
coveralls
worn
over
shorts
and
short­
sleeved
shirts,
chemical­
resistant
gloves,
respirator,
footwear,
eyewear,
and
aprons
for
loaders.
In
MRID
4385250,
subjects
wore
protective
clothing
similar
to
current
label
requirements
including
loaders
who
wore
aprons.
It
should
be
noted
that
the
PHED­
based
exposure
estimates
do
not
reflect
the
use
of
aprons.
Table
15:
Summary
of
Short­/
Intermediate­
Term
Occupational
Handler
Noncancer
Risks
MOEs
Based
On
MRID
438525­
01
(
Open
bag/
open
cab
tractor
&
Current
label
PPE)
MOEs
Based
On
PHED
Engineering
Controls
(
Closed
loading
&
Closed
cab
tractor)

Scenario
Rate
(
lb
ai/
acre)

&
Crop
Area
Treated
(
acres/
day)
Based
On
Rat
RBC
Endpoint
Based
On
Rat
Brain
Endpoint
Based
On
Human
Endpoint
Based
On
Rat
RBC
Endpoint
Based
On
Rat
Brain
Endpoint
Based
On
Human
Endpoint
Loaders
1
Granular:

Solid
broadcast
spreader
6
(
pecans)

4.95
(
citrus)

4.4
(
coffee)

3
(
potato)

3.15
(
cotton)

1.05
(
sorghum)

5
(
ornamentals)
80
80
50
80
80
80
10
13.6
16.4
29.6
27.1
25.8
77.5
130.2
20.3
24.7
44.4
40.7
38.8
116.3
195.3
8.8
10.7
19.2
17.6
16.8
50.4
84.7
14.4
17.5
31.5
28.9
27.5
82.5
138.6
21.7
26.3
47.3
43.3
41.3
123.8
207.9
9.4
11.4
20.5
18.8
17.9
53.6
90.1
Applicators
2
Solid
broadcast
spreader
(
granular)
6
(
pecans)

4.95
(
citrus)

4.4
(
coffee)

3
(
potato)

3.15
(
cotton)

1.05
(
sorghum)

5
(
ornamentals)
80
80
50
80
80
80
10
33.8
40.9
73.7
67.5
64.3
192.9
324.1
50.6
61.4
110.5
101.3
96.5
289.4
486.1
21.9
26.6
47.9
43.9
41.8
125.4
210.6
1.3
1.6
2.9
2.6
2.5
7.5
12.6
2.0
2.4
4.3
3.9
3.8
11.3
18.9
0.9
1.0
1.9
1.7
1.6
4.9
8.2
The
required
uncertainty
factor
which
establishes
a
risk
concern
is
20
for
the
risks
based
on
the
rat
endpoints
and
10
for
the
risks
based
on
the
human
endpoint.

If
MOEs
are
of
concern
and
did
not
exceed
the
required
uncertainty
factor
(
i.
e.,
target
MOE)
they
are
bolded.
Page
49
of
51
7.2.
Incident
Data
Incident
data
were
obtained
from
reports
submitted
to
the
Incident
Data
System
from
1996
through
1999.
The
scientific
literature
on
aldicarb
poisonings
were
reviewed
with
particular
attention
to
the
time
from
onset
of
symptoms
to
recovery,
both
with
and
without
treatment,
doses
associated
with
symptoms
of
carbamate
toxicity
and
sensitivity
of
various
subpopulations.

There
were
a
total
of
27
IDS
reports
involving
at
least
71
people
since
1996
in
IDS.
Four
reports
involved
persons
who
attempted
suicide
by
ingesting
aldicarb;
one
person
died.
The
fourth
report
concerns
the
exposure
to
Tres
Pasitos,
an
aldicarb
product
sold
illegally
as
a
rodenticide
in
New
York
City.
The
exact
number
of
people
involved
is
unclear
­
possibly
as
many
as
40
people.
The
majority
of
the
cases
were
attempted
suicide;
no
deaths
were
reported.

A
total
of
15
men
were
exposed
to
aldicarb
in
an
occupational
setting;
11
cases
had
symptoms
compatible
with
carbamate
poisoning.
All
were
treated
at
a
medical
facility;
five
received
specific
treatment
for
cholinesterase
inhibition
(
atropine).
All
recovered.
The
majority
were
not
wearing
personal
protective
equipment.
All
of
the
cases
occurred
when
workers
were
loading
Temik
or
cleaning
up
equipment
or
an
area
where
the
product
was
stored.
Four
cases
were
in
minors
(
ages
14,
15,
17
and
18).

There
were
three
cases
involving
residential
exposure
to
aldicarb.
One
of
the
cases,
involved
exposure
of
20
people
to
cabbage
salad
contaminated
with
aldicarb.
In
a
second
case,
a
man
ate
berries
from
a
tree
that
had
been
illegally
treated
with
Temik.
His
clinical
symptoms
are
not
discussed
in
the
report;
however,
a
urine
sample
was
positive
for
aldicarb.
In
the
third
case,
a
man
used
Temik
on
his
yard
and
vegetable
garden.
He
was
diagnosed
with
"
amnesia".
No
other
information
on
his
symptoms,
diagnosis
or
outcome
is
provided.

The
PCC
data
demonstrate
that
aldicarb
exposure
is
likely
to
result
in
more
serious
medical
outcome
and
serious
medical
care
than
other
pesticides.
For
occupational
cases,
measures
of
hazard,
such
as
percentage
of
cases
with
moderate
or
severe
outcomes,
percentage
seen
in
a
health
care
facility,
percentage
hospitalized
and
percentage
seen
in
intensive
care
unit
(
ICU)
were
higher
than
all
other
pesticides
in
the
PCC
data
base.
For
non­
occupational
cases
involving
adults
and
older
children,
these
measures
were
increased
even
more.
Patients
exposed
to
aldicarb
were
ten
times
more
likely
to
have
a
life­
threatening
or
fatal
outcome
and
five
times
more
likely
to
need
treatment
in
an
ICU
than
with
all
other
pesticides.
There
were
too
few
cases
to
provide
reliable
estimates
of
proportionate
hazards
to
children
(
less
than
6
years
of
age);
however,
the
pattern
of
risk
in
this
subpopulation
was
similar
to
that
seen
for
non­
occupational
adults
and
older
children.

A
total
of
19
articles
in
the
open
scientific
literature
describing
intentional
or
accidental
poisonings
due
to
aldicarb
exposure
were
reviewed.
Summaries
of
the
articles
are
included
under
Literature
on
Poisonings
in
this
Memorandum.
The
literature
studies
provide
some
limited
insight
into
the
questions
of:
1)
duration
of
symptoms
from
aldicarb
poisoning;
2)
doses
at
which
poisonings
occur;
and
3)
subpopulation
sensitivity.
Concerning
duration
of
symptoms,
there
are
limited
data
on
the
time
between
onset
of
symptoms
and
recovery
without
specific
treatment
with
atropine.
In
one
study
in
which
people
were
exposed
to
cucumbers
contaminated
with
aldicarb,
there
are
data
on
the
duration
of
illness
for
14
people
Page
50
of
51
of
both
sexes,
ages
6­
54.
All
of
the
people
had
symptoms
compatible
with
carbamate
poisoning
which
were
reported
within
one
hour
of
exposure,
however
analysis
of
the
cucumbers
for
aldicarb
was
not
performed.
While
the
duration
of
their
illnesses
was
6
hours
or
less
in
12
of
the
patients,
2
young
girls
(
ages
7
and
16)
were
reported
to
be
ill
for
12
hours.
In
an
outbreak
from
Vancouver,
Canada
involving
contaminated
cucumbers,
it
was
reported
that
recovery
occurred
within
two
to
eight
hours.
In
the
report
from
Louisiana
where
people
ingested
cabbage
salad,
the
illness
reportedly
lasted
a
median
of
4
hours
with
a
range
of
1
to
8
hours.
It
is
unknown
if
the
individuals
in
the
last
two
outbreaks
were
treated
with
atropine.
In
two
studies
in
human
volunteers
submitted
to
EPA,
subjects
recovered
within
6
hours
but
symptoms
were
relatively
mild
(
sweating
and
leg
weakness).
While
many
references
give
less
than
8
hours
as
the
time
to
reversal
of
symptoms
after
carbamate
intoxication,
there
are
data
in
two
young
girls
that
indicate
as
long
as
12
hours
may
be
required.

Concerning
doses
which
produce
symptoms
of
carbamate
poisoning,
this
information
was
not
provided
in
most
of
the
literature
articles.
In
the
report
on
the
cabbage
salad
ingestion,
it
was
calculated
that
a
150
lb.
adult
would
have
ingested
0.2
mg/
kg
body
weight
of
aldicarb.
In
another
study,
the
doses
calculated
from
four
outbreaks,
in
which
aldicarb
was
measured
in
the
food,
ranged
from
0.0011
to
0.060
mg/
kg
body
weight.
In
the
Canadian
cucumber
outbreak,
it
was
possible
to
correlate
the
quantity
of
cucumber
consumed
by
an
individual
with
the
residue
found
in
the
remaining
portion
of
the
same
cucumbers
in
only
a
few
cases.
Typical
symptoms
of
acute
carbamate
poisoning
were
caused
by
aldicarb
residues
in
the
range
of
0.01
to
0.03
mg/
kg
body
weight.

Concerning
subpopulation
sensitivity,
several
articles
have
asserted
that
clinical
signs
and
symptoms
of
carbamate
toxicity
can
differ
in
children
and
adults.
Signs
and
symptoms
commonly
associated
with
carbamate
poisoning
(
SLUDGE
syndrome)
are
more
commonly
observed
in
adults
than
in
children.
This
could
lead
to
misdiagnosis
and
underreporting
of
carbamate
intoxication
in
children.
However,
there
are
no
data
in
the
literature
which
compared
the
doses
at
which
clinical
signs/
symptoms
occurred
in
adults
versus
children
that
would
answer
the
question
about
subpopulation
sensitivity.

8.0
DATA
NEEDS/
LABEL
REQUIREMENTS
8.1
Toxicology
870.3200
21­
day
dermal
toxicity
(
including
RBC/
plasma
ChEI
measures).
28­
day
inhalation
study
(
including
RBC/
plasma/
brain
ChEI
measures).

8.2
Residue
Chemistry
860.1500
Field
trials
residues
in
sorghum
forage
and
cotton
gin
by­
products
(
gin
trash).
[
HED
recommends
cotton
field
trials
include
residues
in
cottonseed,
since
the
available
data
for
this
commodity
are
limited
and
are
of
poor
quality.]

Label
Changes:

Registered
labels
must
reflect
maximum
seasonal
use
rates
(
where
applicable).
Page
51
of
51

The
restriction
against
feeding
grain
sorghum
forage
must
be
removed.

A
10­
month
plantback
interval
(
PBI)
should
be
specified
on
EPA
Reg.
No.
264­
331
for
crops
not
listed
on
the
label.

9.0
SUPPORTING
DOCUMENTATION
The
conclusions
from
the
following
supporting
documents
have
been
incorporated
into
the
aldicarb
preliminary
human
health
risk
assessment:

"
Aldicarb
­
Residue
and
Product
Chemistry
Chapters
of
the
HED
Reregistration
Eligibility
Decision
Document
(
RED)."
[
C.
Swartz
memorandum
dated
6/
02/
00,
DP
Barcode
No.
D266396].

"
Aldicarb
­
Update
of
Incident
Data
Review
of
April
10,
1996"
[
V.
Dobozy
memorandum
dated
6/
24/
00,
DP
Barcode
No.
D267355].

"
Aldicarb
Toxicology
Chapter
for
the
HED
RED,"
[
L.
Taylor
and
W.
Sette
memorandum
dated
8/
20/
02,
DP
Barcode
No.
D266321,
TXR#:
014220].

"
Aldicarb
­
Revised
Anticipated
Residues
and
Dietary
Exposure
Analyses
for
the
HED
Human
Health
Risk
Assessment,"
[
F.
Fort
memorandum
dated
05/
12/
06,
DP
Barcode
No.
D332808].

"
Aldicarb
­
Revised
Occupational
and
Residential
Exposure
Assessment
for
the
Health
Effects
Division
RED,"
[
J.
Dawson
memorandum
dated
1/
11/
05,
DP
Barcode
No.
D311821].