Document ID: EPA-HQ-OPP-2002-0055-0024
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2002-06-24T04:00Z

UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
02/
10/
2000
PREVENTION,
PESTICIDES
AND
MEMORANDUM:
TOXIC
SUBSTANCES
Subject:
Risk
Assessment
and
Reregistration
Eligibility
Decision
(RED)
Documents
for
Disulfoton
(Revised
Risk
Assessment,
Phase
4).
Chem.
No.
032501,
Rereg.
Case
No.
0102
DP
Barcode:
D262883
Sub
DP
Barcode
of
237133
S526236
PC
Code:
032501
CAS
Reg
No.:
274­
04­
4
Caswell
File
No.:
341
From:
David
Anderson,
Risk
Assessor
Health
Effects
Division,
OPP
(7509C)

Through:
Alan
Nielsen,
Branch
Senior
Scientist
Health
Effects
Division,
OPP
(7509C)

To:
Christina
Scheltema,
Chemical
Review
Manager
Special
Review
and
Reregistration
Division,
OPP
(7508W)

This
memorandum
and
six
appendices
constitute
the
revised
(Phase
4)
Risk
Assessment
and
Reregistration
Eligibility
Decision
(RED)
documents
for
disulfoton.
Changes
from
the
previous
risk
assessment
(Phase
3)
include
incorporation
of
new
data
and
information
from
revised
and
updated
appendices.
Revisions
to
the
appendices
include:
major
changes
in
the
acute
and
chronic
dietary
risk
to
include
probabilistic
acute
dietary
risk
and
use
of
monitoring
data
for
residues
of
disulfoton
and
metabolites
of
concern
in
food
(Tier
3);
minor
changes
in
the
occupational/
residential
exposure
chapter
related
to
public
comment;
inclusion
of
the
new
acute
delayed
neurotoxicity
hen
study
in
the
toxicology
chapter;
the
revised
hazard
identification
assessment,
and
no
changes
in
the
product
and
residue
chemistry
chapter;
or
the
incident
report
for
disulfoton.

Consideration
is
also
given
to
the
Food
Quality
Protection
Act
of
1996
(FQPA).
Cumulative
risk
assessment
from
other
pesticides
that
have
a
common
mechanism
of
toxicity
will
be
addressed
at
a
future
date.
ii
The
attachments
include
the
Revised
Toxicology
Chapter
for
the
Disulfoton
RED
(David
G
Anderson,
Appendix
1);
the
most
recent
Hazard
Identification
Assessment
Review
Committee
(HIARC,
1/
19/
2000)
Report
for
Disulfoton:
Revisit
(
David
G
Anderson,
Appendix
2);
The
FQPA
Safety
Factor
Committee
Report
for
Disulfoton
(Brenda
Tarplee,
1/
24/
2000,
Appendix
3);
the
revised
Disulfoton:
Acute
and
Chronic
Dietary
Risk
Assessment
(William
O.
Smith,
Appendix
4);
the
revised
Product
Chemistry
and
Residue
Chemistry
Chapters
for
Disulfoton
RED
(John
Abbots/
Ken
Dockter,
Appendix
5);
the
revised
Occupational/
Residential
Exposure
Chapter
(ORE)
for
Disulfoton
RED
(Jonathan
Becker,
Appendix
6)
and
Memorandum
from
Jerome
Blondell
to
Jonathan
Becker
of
HED
(3/
25/
1998),
Review
of
Disulfoton
Incidence
Reports
(Jerome
Blondell,
Appendix
6).
HUMAN
HEALTH
RISK
ASSESSMENT
Disulfoton
U.
S.
Environmental
Protection
Agency
Office
of
Pesticide
Programs
Health
Effects
Division
(7509C)

David
Anderson,
Risk
Assessor
February
10,
2000
HUMAN
HEALTH
RISK
ASSESSMENT
Disulfoton
Phase
4
Risk
Assessment
Team:

Lead
Risk
Assessor:
DavidAnderson
Dietary
Risk:
William
O.
Smith
Occupational
and
Jonathan
Becker
Residential
Exposure:

Epidemiology:
Jerome
Blondell
Toxicology:
DavidAnderson
Management:

Senior
Scientist:
Alan
Nielsen
Branch
Chief:
Pauline
Wagner
Division
Director:
Margaret
J.
Stasikowski,
Date
TABLE
OF
CONTENTS
1.
0
EXECUTIVESUMMARY
..............................................
4
2.
0
PHYSICAL/
CHEMICALPROPERTIESCHARACTERIZATION................
8
3.
0
HAZARDCHARACTERIZATION........................................
8
3.1
Hazard
Profile
..................................................
8
3.
2
EndpointSelection..............................................
13
3.
3
FQPAConsiderations............................................
14
4.
0
EXPOSURE
ASSESSMENT
...........................................
15
4.
1
SummaryofRegisteredUses
......................................
15
4.
2
DietaryExposurefromFood
......................................
15
4.2.1
Acute
and
Chronic
Dietary
Exposure
Methodology
and
Characterization
..........................................
16
4.
2.
2
AcuteDietaryRisk(
Food)
..................................
17
4.
2.
3
ChronicDietaryRisk(
Food).................................
18
4.
3
WaterExposure(
DrinkingWaterSources)............................
19
4.
3.
1
SurfaceWater............................................
19
4.
3.
2
Groundwater.............................................
20
4.
3.
3
MonitoringData
..........................................
20
4.
3.
4
DWLOCsforAcuteandChronicExposure
.....................
20
4.
3.
4.
1AcuteDWLOCs
....................................
21
4.
3.
4.
2ChronicDWLOCs...................................
22
4.
4
Occupational/
ResidentialExposure..................................
23
4.
4.
1
AssumptionsforOccupationalHandler
Exposure
.................
23
4.
4.
2
OccupationalHandler
ExposureandCharacterization..............
26
4.
4.
3
OccupationalHandler
RisksofConcern
........................
26
4.
4.
4
DataGaps...............................................
28
4.
4.
5
DataQualityandConfidenceinAssessment
.....................
28
4.
4.
6
PostapplicationExposure
...................................
29
4.
4.
7
HumanIncidenceInformation................................
30
4.
5
ResidentialExposure
............................................
30
4.
5.
1
Handler.................................................
30
4.
5.
2
ResidentialHandler
ExposureScenarios­
DataandAssumptions
......
31
4.
5.
3
PostapplicationResidentialExposureandRisk
...................
33
4.
5.
4
PotentialSprayDrift
.......................................
34
5.0
AGGREGATE
RISK
(FOOD,
WATER
AND
RESIDENTIAL)
.................
34
6.0
ENDOCRINE
MODULATION
..........................................
35
7.
0
CUMULATIVE
EXPOSURE
ANDRISK..................................
35
2
8.
0
REQUIREDDATA
..................................................
36
9.
0
CODEX............................................................
36
10.
0
APPENDICES.......................................................
37
Appendix1:
ToxicologyChapter
fortheDisulfotonRED(
DavidG.
Anderson)
...........
37
Appendix
2:
The
Hazard
Identification
Assessment
Review
Committee
Report
for
Disulfoton(
Revisit)(
DavidG.
Anderson).
.........................
37
Appendix
3:
The
FQPA
Safety
Factor
Committee
Report
on
Disulfoton
(Brenda
Tarplee).
.
.
.
37
Appendix
4:
The
Revised
Disulfoton:
Acute
and
Chronic
Dietary
Risk
Assessment
(Includes
MRID
#
44821701
&
44821702,
Chem.
No.
032501;
William
O.
Smith)
.....
37
Appendix
5:
Product
Chemistry
and
Residue
Chemistry
Chapters
for
the
DisulfotonRED(
JohnAbbots/
KenDockter)
..........................
37
Appendix
6:
Occupational/
Residential
Exposure
Chapter
for
the
Disulfoton
RED
(Jonathan
Becker)
and
Memorandum
from
Jerome
Blondell
to
Jonathan
Becker
of
HED
(3/
25/
1998):
Review
of
Disulfoton
Incidence
Reports
(Jerome
Blondell)
.....
37
LIST
OF
TABLES
Table1:
AcuteToxicityofDisulfotonTechnical
..............................
9
Table2:
ToxicityProfileofDisulfotonTechnical.............................
11
Table3:
EndpointsSelectedfor
AcuteandChronicDietaryExposure.............
13
Table
4:
Endpoints
Selected
for
Occupational
and
Residential
Exposure
Scenarios
.
.
.
14
Table
5:
Common
and
Chemical
Names
of
Identified
Disulfoton
Tolerance
Residues
.
.
16
Table
6:
Acute
Dietary
Risk
Estimates
(aPAD
=
0.
0025
mg/
kg/
day)
..............
18
Table
7:
Chronic
Dietary
Risk
Estimates
(cPAD
=
0.
00013
mg/
kg/
day)
...........
19
Table
8:
DWLOC
Values
for
Total
Acute
Dietary
Exposure
at
the
99.9
th
percentile
(DWLOC
acute
)
........................................
21
Table
9:
DWLOC
Values
for
Total
Chronic
Dietary
Exposure
(DWLOC
chronic
)......
22
3
Table
10:
Occupational
Handler
Total
Exposure
(dermal
and
inhalation)
to
Disulfoton
for
Short­
and
Intermediate­
Term
Exposure
with
Baseline,
PPE
or
EngineeringControls(
EngC)
...................................
24
Table
11:
Disulfoton
Intermediate­
Term
Surrogate
Occupational
Postapplication
Assessment(
RangeFinder)
for
HighApplicationRates
...............
29
Table12:
ResidentialHandlerShort­
termRisksfromDisulfotonatBaseline
........
32
1
In
this
document,
risk
estimates
are
presented
as
a
percentage
of
the
population
adjusted
dose
(aPAD
or
cPAD)
and
occupational/
residential
risk
is
estimated
as
Margin
of
Exposure
(MOE).
Dietary
exposure
greater
than
100
percent
of
the
PAD
is
a
risk
of
concern
and
MOEs
less
than
100
are
a
risk
of
concern
for
occupational/
residential
and
aggregate
exposure
(water,
diet
and
residential).

4
1.0
EXECUTIVE
SUMMARY
1
This
risk
assessment
is
being
conducted
on
the
organophosphate
pesticide,
disulfoton,
for
reregistration.
Disulfoton
(O,
O­
diethyl
S­[
2­(
ethylthio)
ethyl]
phosphorodithioate)
is
an
acaricide
and
insecticide
currently
registered
by
Bayer
Corporation
for
application
to
grains,
vegetables,
cotton,
and
other
crops.

Technical
disulfoton
contains
98.5
percent
active
ingredient
(ai).
Formulations
include
the
emulsifiable
concentrate
(17.5
percent­
85
percent
ai)
and
the
granular
(0.
37
percent­
15
percent
ai).
The
two
percent
and
15
percent
granular,
95
percent
ready­
to­
use
(RTU),
and
the
8
lb/
gal
emulsifiable
concentrate
(EC)
formulations
are
the
disulfoton
formulation
classes
registered
for
use
on
food/
feed
crops.

Applications
are
made
with
ground
and
aerial
equipment,
as
well
as
hand­
held
equipment.
Application
rates
range
from
0.
005
lb
ai/
1000
ft
2
to
over
100
lb
ai/
A.
Disulfoton
is
registered
for
use
on
both
occupational
and
non­
occupational
use­
sites
including,
but
not
limited
to,
food
and
feed
crops,
nut
trees,
non­
bearing
fruit
trees,
ornamental
flowers,
shrubs
and
trees,
potted
plants,
residential
rose
bushes,
and
residential
vegetable
gardens.
The
registrant
has
agreed
to
discontinue
disulfoton
use
on
vegetable
gardens.

Exposure
to
disulfoton
and
its
cholinesterase
inhibiting
metabolites
occurs
through
exposure
to
residues
in
food
and
water;
through
mixing,
loading,
application,
and
other
handling
procedures;
and
from
dislogeable
residues
on
treated
plants.
Residential
exposure
can
occur
through
food,
water,
home
garden
use,
and
flower
and
ornamental
disulfoton
application
and
uses.
The
potential
problem
of
exposure
to
children
from
hand­
to­
mouth
exposure
in
treated
areas
was
shown
to
be
below
the
Agency's
level
of
concern.
Introduction
2
PAD
=
Population
Adjusted
Dose
=
Acute
or
Chronic
RfD
FQPA
Safety
Factor
5
Toxicity
endpoints
selected
for
risk
assessment
are
based
on
cholinesterase
inhibition.
Disulfoton
is
an
organophosphate,
causing
cholinesterase
inhibition
at
low
dose
levels
and
across
species.
No
neuropathy
is
seen
in
any
of
the
studies.
Brain,
plasma
and
erythrocyte
cholinesterase
inhibition
all
occurred
at
the
same
dose
level
in
many,
but
not
all,
studies.
Females
are
slightly
more
sensitive
than
males.

An
uncertainty
factor
(UF)
of
100X
was
applied
to
the
risk
assessment
to
account
for
inter­
and
intraspecies
variation.
The
FQPA
safety
factor
(as
required
by
the
Food
Quality
Protection
Act
of
August
3,
1996)
was
reduced
to
1X
because
disulfoton
studies
show
no
increased
susceptibility
to
infants
and
children,
and
no
neuropathy
was
seen
in
any
study.

Current
reassessed
tolerances
are
based
on
submitted
field
trial
data
on
disulfoton,
its
oxygenated
metabolite
(demeton­
S),
and
the
corresponding
sulfoxide
and
sulfone
metabolites.
In
plants,
disulfoton
is
rapidly
converted
to
disulfoton
sulfoxide
and
sulfone
or
disulfoton
oxygen
analog
sulfoxide
and
sulfone
(demeton­
S
sulfone).
When
the
sulfur­
containing
side
chain
is
removed,
the
products
are
no
longer
cholinesterase
inhibitors.
The
tolerance
expression
for
disulfoton
is
composed
of
disulfoton
and
its
five
metabolites
expressed
as
disulfoton.
This
risk
assessment
includes
all
supported
crops
and
use
sites
listed
on
the
current
labels.

The
revised
acute
(probabilistic
assessment)
and
chronic
dietary
exposure
assessment
represent
the
most
highly
refined
dietary
assessments
possible
with
the
data
available.
The
revised
assessments
were
based
on
data
from
the
U.
S.
Department
of
Agriculture
(USDA)
Continuing
Survey
of
Food
Intake
by
Individuals,
monitoring
data
from
USDA
Pesticide
Data
Program
(PDP)
and
the
Food
and
Drug
Administration
(FDA)
monitoring
program,
field
trial
data,
processing
factors
from
the
registrant,
published
literature,
and
percent
crop
treated
information.
The
monitoring
data
showed
few
detections
for
disulfoton
or
its
five
metabolites,
thus
anticipated
residues
were
estimated
by
one­
half­
the­
limit­
of­
detection
(½
LOD)
for
disulfoton
and
its
metabolites
that
were
likely
to
be
present
for
all
non­
detectable
residues.

The
acute
dietary
exposure
is
below
the
Agency's
level
of
concern
(<
100
percent
acute
Population
Adjusted
Dose,
or
aPAD
2
).
The
most
highly
exposed
groups
are
children
one
to
six
years
old
and
infants
less
than
one
year,
both
with
9.
6
percent
(at
the
99.9
th
percentile)
of
the
aPAD.
The
remaining
groups
show
an
acute
risk
that
ranges
from
4.7
percent
to
8.
8
percent
of
the
aPAD
at
the
99.9
th
percentile
exposure.
Toxicity,
Dose­
Response,
and
the
FQPA
Factor
Dietary
Risk
Assessment
6
The
chronic
dietary
exposure
is
below
the
Agency's
level
of
concern
(<
100
percent
chronic
Population
Adjusted
Dose,
or
cPAD).
The
most
highly
exposed
group
is
children
one
to
six
years
old
with
3.
5
percent
of
the
cPAD.
The
remaining
groups
show
a
chronic
dietary
risk
that
ranges
from
0.87
percent
to
2.
4
percent
of
the
cPAD.

Most
monitoring
data
for
drinking
water
were
inadequate;
therefore,
drinking
water
levels
of
comparison
(DWLOCs)
were
calculated
and
compared
with
surface
water
concentration
levels
estimated
from
the
Tier
2
PRZM/
EXAMS
model,
and
groundwater
concentration
levels
estimated
from
the
SCI­
GROWmodel
of
disulfoton
in
water.
Exposure
to
disulfoton
through
drinking
water
may
be
of
concern
when
calculated
DWLOCs
are
lower
than
the
estimated
environmental
concentrations
of
disulfoton
in
water.
PRZM/
EXAMS
and
SCI­
GROW
model
estimates
are
conservative
and
thus
tend
to
over
estimate
concentration
levels
of
disulfoton
that
may
be
present
in
ground
and
surface
water.
The
limited
quality
assured
monitoring
data
supported
the
SCIGROW
modeling
values
for
groundwater
and
showed
that
SCI­
GROW
values
were
reasonably
accurate
for
vulnerable
areas.

Modeled
surface
water
estimates
are
higher
than
the
acute
DWLOCs
for
the
highest
exposed
group
through
food
(children
one
to
six
years),
which
indicates
that
disulfoton
in
surface
water
may
be
an
acute
risk
of
concern.
Modeled
groundwater
estimates
are
lower
than
the
acute
DWLOC
for
the
most
exposed
population,
which
indicates
that
disulfoton
and
residues
in
groundwater
may
not
be
of
concern.
For
chronic
exposure,
surface
water
and
groundwater
estimates
are
higher
than
the
chronic
DWLOCs
for
the
highest
exposed
group
through
food
(children
one
to
six
years),
which
indicates
that
disulfoton
and
residues
in
surface
and
groundwater
may
be
a
chronic
risk
of
concern.

Endpoints
used
for
occupational
and
residential
assessments
were
based
on
cholinesterase
inhibition
seen
in
a
dermal
study
for
short­
term
exposure
(one
to
seven
days)
and
an
oral
study
for
intermediate
exposure
(one
week
to
several
months).
A
36
percent
oral
equivalent
dermal
absorption
value
was
used
for
the
intermediate
exposure
assessment.
An
inhalation
endpoint
was
based
on
an
inhalation
study
for
both
short­
term
and
intermediate­
term
exposure.

For
most
occupational
pesticide
handler
scenarios
exceed
the
Agency's
level
of
concern.
With
engineering
controls
in
place,
only
four
of
the
20
occupational
scenarios
showed
risks
that
do
not
exceed
the
Agency's
level
of
concern.
Based
on
acute
toxicity
category
of
I,
postapplication
reentry
intervals
(REIs)
are
48
hours
after
treatment
with
liquid
disulfoton
at
4.
0
lb
ai/
A
or
lower
rates
of
application.
Reentry
intervals,
using
standard
values
are
estimated
to
be
28
to
36
days
at
higher
rates
of
application
of
disulfoton.
Drinking
Water
Assessment
Occupational
and
Residential
Risk
Assessment
7
Scenarios
that
do
not
exceed
the
Agency's
level
of
concern
for
residential
handler
uses
are
limited
to
ornamentals
and
garden
use
at
the
lowest
application
rates.
Postapplication
risks
for
adult
homeowners
were
estimated
to
be
low.
Toddlers,
with
hand­
to­
mouth
exposures
in
treated
areas,
do
not
exceed
the
Agency's
level
of
concern.

An
aggregate
risk
assessment
(food,
drinking
water,
and
residential)
was
not
conducted
for
disulfoton.
All
of
the
residential
exposure
scenarios
specified
on
the
label
exceed
the
Agency's
level
of
concern
(MOEs
<
100)
at
the
maximum
use
rate.
Estimated
environmental
concentrations
of
disulfoton
residues
in
water
are
above
the
Agency's
level
of
concern.
Any
aggregation
of
exposure
to
disulfoton
through
residential
uses
and
drinking
water
would
only
serve
to
increase
the
Agency's
level
of
concern.

The
Agency
is
in
the
process
of
formulating
guidance
for
conducting
cumulative
assessment.
When
this
guidance
is
complete,
the
cumulative
risk
from
all
organophosphates
will
be
assessed
where
appropriate.

Some
minor
revisions
in
the
tolerance
expression
are
required
for
harmonization
with
Codex.
Tolerances
that
are
currently
expressed
as
demeton­
S
should
be
expressed
as
disulfoton.

In
summary,
exposure
to
disulfoton
in
the
diet
is
below
the
Agency's
level
of
concern
for
both
acute
and
chronic
food
exposure,
but
most
occupational
and
residential
exposures
exceed
the
Agency's
level
of
concern
even
with
engineering
controls
(when
applicable).
Acute
and
chronic
DWLOCs
for
surface
water
may
be
a
risk
of
concern,
and
chronic
DWLOC
compared
with
the
groundwater
estimates
may
show
a
risk
of
concern.
Aggregate
and
Cumulative
Risk
Assessment
Codex
Conclusion
8
P
S
S
S
CH
3
OC
2
H
5
H
5
C
2
O
2.0
PHYSICAL/
CHEMICAL
PROPERTIES
CHARACTERIZATION
Disulfoton
is
a
colorless
to
yellow
liquid
with
a
boiling
point
of
62

C
at
0.
01
mm
Hg,
vapor
pressure
1.8x10
­4
millibars
at
20

C.
The
vapor
pressure
of
disulfoton
is
moderately
high,
suggesting
that
inhalation
of
disulfoton
may
contribute
to
exposure
under
certain
circumstances.
Disulfoton
is
soluble
in
water
at
25
ppm
at
20

C
and
is
miscible
in
dichloromethane
,
hexane,
2propranol
and
toluene
at
20

C.
Disulfoton
is
an
organophosphate
insecticide
with
a
molecular
weight
of
274.4
g/
mole.
The
systematic
name
is
O,
O­
diethyl
S­[
2­
ethylthio)
ethyl]
phosphorodithioate
with
a
trade
name
of
Di­
Syston
(R)
.
The
structure
is
presented
below.

Empirical
Formula:
C6H19O2PS3
Molecular
Weight:
274.4
g/
mole
CAS
Registry
No.:
298­
04­
4
Chemical
No.:
032501
3.0
HAZARD
CHARACTERIZATION
3.1
Hazard
Profile
Disulfoton
is
acutely
toxic
by
the
oral,
dermal
and
inhalation
routes
(Table
1).
Disulfoton
was
too
toxic
for
guideline
studies
on
primary
eye,
skin
irritation
and
dermal
sensitization
to
be
conducted.
The
data
requirements
were
waived
because
of
the
severity
of
the
anticipated
results
and
the
most
severe
categories
should
be
assumed
for
eye
and
skin
irritation.

The
mode
of
action
of
disulfoton
is
inhibition
of
cholinesterase.
In
all
of
the
toxicity
studies
evaluated
in
this
hazard
assessment,
the
LOAEL
and
NOAEL
were
established
by
the
inhibition
of
cholinesterase
(the
basis
for
all
regulatory
endpoints).
Clinical
signs,
such
as
muscle
fasciculation
and
tremors
are
seen
either
at
higher
dose
levels
or
at
the
LOAEL
some
studies.
All
three
cholinesterases
(plasma,
erythrocyte
and
brain)
are
inhibited
at
the
LOAEL
in
at
least
one
study
in
the
rat,
mouse,
rabbit
and
dog
and
are
likely
to
occur
across
species.
Slight
species
differences
occur,
but
the
differences
may
be
due
to
normal
variation
and
differences
in
the
duration
of
the
studies
conducted
in
different
species.
Adult
females
appear
to
be
slightly
more
sensitive
than
males.
In
a
six­
month
study
in
rats
(MRID#
43058401),
cholinesterase
inhibition
was
seen
only
in
females
at
the
LOAEL.
9
Table
1:
Acute
Toxicity
of
Disulfoton
Technical
Guideline
No.
Study
Type
MRID
#(
S).
Results
Toxicity
Category
81­
1
Acute
Oral
Acc#
072293,
Doc#
003958,
p41
LD50
=
M:
6.
2
mg/
kg;
F:
1.9
mg/
kg
I
81­
2
Acute
Dermal
Acc#
07793,
Doc#
03958,
p71
&
004223,
p24
LD50
=
M:
15.9
mg/
kg;
F:
3.6
mg/
kg
I
81­
3
Acute
Inhalation
Acc#
258569,
Doc#
05789
LC50
=M:
0.
06mg/
L;
F:
0.015
mg/
L
I
81­
4
Primary
Eye
Irritation
Data
requirement
waived.
Doc#
03958,
p12;
004223,
p14
I
(assumed)

81­
5
Primary
Skin
Irritation
Data
requirement
waived.
Doc#
03958,
p12;
004223,
p14
I
(assumed)

81­
6
Dermal
Sensitization
Data
requirement
waived.
Doc#
03958,
p12
Sensitizer
(assumed)

81­
7
Acute
Delayed
Neurotoxicity
MRID#
44996401,
Doc#
013957
Negative
for
OPIDP
The
cholinesterase
endpoints
between
acute
and
chronic
studies
in
rats
all
are
approximately
within
a
10
fold
exposure
level.
Longer
exposure
always
showed
cholinesterase
inhibition
at
a
lower
dose
level.
Clinical
signs
occurred
in
test
animals
at
the
same
dose
level
as
cholinesterase
inhibition
in
the
acute
neurotoxicity
study,
whereas
in
the
90­
day
neurotoxicity
study,
cholinesterase
inhibition
occurred
at
a
lower
dose
level.
Motor
activity
was
affected
at
lower
dose
levels
in
the
90­
day
study
than
in
the
acute
study,
but
no
treatment
related
or
significant
neuropathology
occurred
either
acutely
or
in
the
90­
day
studies.

No
definitive
endocrine
disruption
was
seen
in
any
of
the
studies.
Absolute
testes
and
ovarian
weights
were
decreased
(of
unknown
cause)
at
the
highest
dose
level
and
in
the
presence
of
cholinesterase
inhibition
and
well
above
the
NOAEL
in
the
chronic
rat
study.
See
Section
6.
0
on
Endocrine
Modulation
for
the
Agency's
plans
for
implementation
of
tests
on
pesticides
for
possible
endocrine
affects.

There
is
an
adequate
dermal
absorption
study
in
rats
and
an
adequate
21­
day
dermal
study
in
rabbits
showing
cholinesterase
inhibition
(plasma,
erythrocyte
and
brain).

Acceptable
studies
in
rats
and
mice
did
not
demonstrate
evidence
of
carcinogenicity.
10
Disulfoton
is
positive
in
some
mutagenicity
studies
without
activation,
but
negative
or
weakly
positive
with
activation
in
most.
The
mutagenicity
database
is
complete
for
the
pre­
1990
required
three
mutagenicity
categories
and
the
in
vivo
database
support
a
lack
of
concern
for
the
mutagenicity
of
disulfoton.

The
metabolism
of
disulfoton
was
studied
in
the
rat.
Disulfoton
was
found
to
be
rapidly
absorbed
and
excreted
with
over
95
percent
of
the
administered
C
14
labeled
disulfoton
being
recovered
in
the
urine.
Approximately
90
percent
of
the
disulfoton
was
excreted
within
24
hours.
Less
than
two
percent
was
recovered
from
the
feces.
Bioaccummulation
was
not
observed
with
less
than
0.3
percent
being
recovered
in
tissues
and
less
than
one
percent
being
recovered
in
the
carcass.
A
major
metabolite
was
incompletely
identified,
but
it
co­
chromatographed
with
1­(
ethylsulfonyl)­
2­(
methylsulfonyl)
ethane,
a
fully
oxidized
form
of
the
putative
hydrolysis
product.
The
toxic
metabolites
of
disulfoton
are
disulfoton
sulfoxide,
disulfoton
sulfone,
disulfoton
oxygen
analog
(demeton­
S),
disulfoton
oxygen
analog
sulfoxide
and
disulfoton
oxygen
analog
sulfone.
The
Metabolism
Committee
determined
that
the
residues
to
be
regulated
in
plant
and
animal
commodities
are
disulfoton
and
these
five
disulfoton
metabolites.

There
is
no
increased
susceptibility
to
fetuses
or
pups
in
acceptable
developmental
and
reproductive
toxicity
studies
in
the
rabbit
or
rat.
In
the
study
on
reproduction,
cholinesterase
was
inhibited
(plasma,
erythrocyte
and
brain)
in
parents
at
lower
dose
levels
than
in
pups.
Pup
death
occurred
at
the
highest
dose
tested
in
the
study
on
reproduction.
The
deaths
were
attributed
to
an
inadequate
milk
supply
and
maternal
care
failure.
In
the
developmental
toxicity
study
in
the
rat,
developmental
toxicity
occurred
at
higher
doses
than
caused
toxicity
in
dams.
Developmental
toxicity
in
the
rat
was
seen
in
the
form
of
incomplete
ossification,
but
no
developmental
toxicity
was
seen
in
the
rabbit
at
the
adequate
dose
levels
administered.
No
fetal
or
offspring
sensitivity
issues
or
neuropathology
was
identified
in
the
toxicology
database.

The
toxicity
profile
of
disulfoton
is
presented
in
Table
2.
The
toxicity
database
for
disulfoton
is
adequate
to
support
reregistration.
The
database
is
of
generally
high
quality
with
better
than
average
consistency
in
data
on
the
dose
and
treatment
relationship
of
plasma,
erythrocyte
and
brain
cholinesterase
inhibition
which
are
the
regulatory
endpoints
of
concern.

All
the
toxicity
data
used
to
select
endpoints
for
regulation
were
acceptable
guideline
studies.
11
Table
2:
Toxicity
Profile
of
Disulfoton
Technical
Study
Type
MRID
No.
Results
Acute
Neurotoxicity
­
Rat
42755801
NOAEL
(Clinical
signs
and
ChE
Inhibition)
=
0.
25
mg/
kg/
day
LOAEL
(Clinical
signs
and
ChE
Inhibition)
=
0.
75
mg/
kg/
day
Acute
Inhalation
­
Rat
Acc#
258569
NOAEL
(ChE
Inhibition)
=
0.
0005
mg/
L
LOAEL
(ChE
Inhibition)
=
0.
0018
mg/
L
21­
Day
Dermal
ToxicityRabbit
00162338
NOAEL
(Systemic)
=
1.
6
mg/
kg/
day
LOAEL
(Systemic)
=
6.5
mg/
kg/
day
NOAEL
(ChE
Inhibition)
=
0.
4
mg/
kg/
day
LOAEL
(ChE
Inhibition)
=
1.
6
mg/
kg/
day
Subacute
Inhalation
­
Rat
(3­
5
day
exposures)
Acc#
258569
NOAEL
(ChE
Inhibition)
=
Not
established
LOAEL
(ChE
Inhibition)
=
0.
0005
mg/
L
Subchronic
Inhalation
­
Rat
41224301
NOAEL
=
(ChE
Inhibition)
=
0.
00016
mg/
L
LOAEL
=
(ChE
Inhibition)
=
0.
0014
mg/
L
Subchronic
Neurotoxicity
­Rat
42977401
NOAEL
(Clinical
signs)
=
0.
071
mg/
kg/
day
LOAEL
(Clinical
signs)
=
0.
315
mg/
kg/
day
(HDT)
NOAEL
(ChE
Inhibition)=
Not
established.
LOAEL
(ChE
Inhibition)=
<0.071mg/
kg/
day
(LDT)

Subchronic­
Feeding­
Rat
Data
waived
because
an
adequate
chronic
study
was
available
Special
6­
Month
Cholinesterase
­
Rat

Non­
guideline
study
43058401
NOAEL
(ChE
Inhibition)
=
0.
03
mg/
kg/
day
LOAEL
(ChE
Inhibition)
=
0.
07
mg/
kg/
day
Subchronic­
Feeding­
Dog
Data
waived
because
an
adequate
chronic
dog
study
was
available
Chronic­
Feeding­
Dog
(1­
year)
44248002
NOAEL
(ChE
Inhibition)=
0.
013
mg/
kg/
day
LOAEL
(ChE
Inhibition)=
0.
094
mg/
kg/
day
Chronic­
Feeding­
Dog
(1­
year)
00073348
NOAEL
=
(ChE
Inhibition)
=
0.
25
mg/
kg/
day
LOAEL
(ChE
Inhibition)
=
0.
05
mg/
kg/
day
Chronic
Toxicity/
Carcinogenicity
Rat
00146873
41850001
41850002
NOAEL
(systemic)
=
0.
04
mg/
kg/
day
LOAEL
(systemic)
=
0.165
mg/
kg/
day
(HDT)
NOAEL
(ChE
Inhibition)
=
Not
demonstrated
LOAEL
(ChE
Inhibition)
=
0.
04
mg/
kg/
day
(LDT)
No
evidence
of
carcinogenicity
Carcinogenicity
­
Mouse
00129456
00139598
NOAEL
(ChE
Inhibition)
=
0.
6
mg/
kg/
day
LOAEL
(ChE
Inhibition)
=
2.
4
mg/
kg/
day
(HDT)
No
evidence
of
carcinogenicity
Developmental
Toxicity­
Rat
00129458
Maternal:
NOAEL
=
0.1
mg/
kg/
day
LOAEL
=
0.3
mg/
kg/
day
Developmental:
NOAEL
=
0.
3
mg/
kg/
day
LOAEL
=
1.0
mg/
kg/
day
Table
2:
Toxicity
Profile
of
Disulfoton
Technical
Study
Type
MRID
No.
Results
12
Developmental
Toxicity­
Rabbit
00147886
Maternal:
NOAEL
=
1.0
mg/
kg/
day
LOAEL
=
1.5
mg/
kg/
day
Developmental:
NOAEL=
>3.
0
mg/
kg/
day
LOAEL
=
>3.
0
mg/
kg/
day
Reproductive
Toxicity
­
Rat
44440801
Parental/
NOAEL
=
Not
established
Systemic:
LOAEL
=
0.025
mg/
kg/
day
(LDT)

Offspring:
NOAEL
=
0.
10
mg/
kg/
day
LOAEL
=
0.45
mg/
kg/
day
(HDT)

Reproductive
Toxicity
­
Rat
00157511
Parental/
NOAEL
=
0.04
mg/
kg/
day
Systemic:
LOAEL
=
0.12
mg/
kg/
day
Offspring:
NOAEL
=
0.
04
mg/
kg/
day
LOAEL
=
0.12
mg/
kg/
day
Gene
Mutation

Salmonella
00028625
Non­
mutagenic
(±)
activation.

Gene
Mutation
­
HGPRT
40638401
Assumed
+
because
tested
at
partially
soluble
conditions.

Chromosomal
Aberrations
43615701
Non­
mutagenic
(±)
activation.

Sister
Chromatide
Exchange
40495001
Non­
mutagenic
(­)
activation,
but
(+)
with
activation.

Sister
Chromatide
Exchange
Acc#
072293
Non­
mutagenic
(±)
activation
Unscheduled
DNA
Synthesis
Acc#
028625
Mutagenic
(+)
activation,
but
non­
mutagenic
(­)
activation
Mouse
Lymphoma
EPA­
600/
1­
84­
003
Mutagenic
(+)
activation,
but
non­
mutagenic
(+)
activation.

Mouse
Micronucleus
EPA­
600/
1­
84­
003
Non­
mutagenic.

Sister
Chromatide
Exchange
EPA­
600/
1­
84­
003
Weakly
mutagenic
(­)
activation,
but
non­
mutagenic
(+)
activation
Table
2:
Toxicity
Profile
of
Disulfoton
Technical
Study
Type
MRID
No.
Results
13
Metabolism­
Rat
42565101
Greater
than
90
percent
of
the
administered
radioactivity
was
metabolized
completely
and
eliminated
within
24
hours.
About
95
percent
of
the
radiolabel
was
recovered
in
the
urine,
<2
percent
in
the
feces,
<0.
3
percent
in
tissues
and
<1
percent
in
the
carcas.
No
bioaccummulation
was
noted.
Sex
related
differences
were
attributed
to
different
metabolic
rates
rather
than
different
profiles.
The
(toxicologically
inactive)
major
and
minor
metabolites
were
produced
by
hydrolysis
of
oxygen
metabolites.

Dermal
Absorption
­
Rats
43360201
Dermal
absorption
is
considered
to
be
36
percent
at
10
hours
3.2
Endpoint
Selection
Table
3
shows
the
acute
and
chronic
dietary
exposure
endpoints.
Table
4
shows
the
NOAELs,
endpoints,
and
MOEs
selected
for
residential
and
occupational
exposure.

Table
3:
Endpoints
Selected
for
Acute
and
Chronic
Dietary
Exposure
Exposure
Scenario
Study
NOAEL
1
Endpoint
Acute
dietary
Acute
neurotox/
rat
(81­
8)
0.25
mg/
kg/
day
Cholinesterase
inhibition
and
muscle
fasciculation
was
seen
in
females
at
0.
75
mg/
kg/
day
Acute
dietary
PAD
=
0.0025
mg/
kg
(NOAEL/
100)

Chronic
dietary
Chronic/
Dog
(83­
1)
0.013
mg/
kg/
day
Plasma,
erythrocyte,
brain
and
retinal
cholinesterase
inhibition
was
seen
in
females
at
0.094
mg/
kg/
day
Chronic
dietary
PAD
=
0.00013
mg/
kg/
day
(NOAEL/
100)
14
Table
4:
Endpoints
Selected
for
Occupational
and
Residential
Exposure
Scenarios
Exposure
Scenario
Study
NOAEL
1
Endpoint
Short­
term
(dermal)
21­
day
dermal/
rabbit
(82­
3)
0.4
mg/
kg/
day
Plasma,
erythrocyte
and
brain
cholinesterase
inhibition
was
seen
in
males
and
females
at
1.6
mg/
kg/
day
Correction
for
dermal
absorption
unnecessary
(MOE
necessary
is
100)

Intermediateterm
(dermal)
6­
month
oral
chronic/
rat
0.03
mg/
kg/
day
2
Plasma,
erythrocyte
and
brain
cholinesterase
inhibition
was
seen
in
females
at
0.
7
mg/
kg/
day
Correction
for
oral
to
dermal
exposure
necessary
(MOE
necessary
is
100)

Long­
term
(dermal)
Chronic
oral/
dog
(83­
1)
0.013
mg/
kg/
day
2
Plasma,
erythrocyte,
brain
and
retinal
cholinesterase
inhibition
was
seen
in
females
at
0.094
mg/
kg/
day
Correction
for
oral
to
dermal
exposure
necessary
(MOE
necessary
is
100)

All
Time
Periods
ShortIntermediate
and
Long­
term
(inhalation)
90­
day
inhal/
rat
(82­
4)
0.00016
mg/
L
Plasma,
erythrocyte
and
brain
cholinesterase
inhibition
was
seen
in
males
and
females
at
0.0014
mg/
L
Inhalation
(MOE
necessary
is
100)

1
=
No
Observed
Adverse
Effect
Level.
2
=
Appropriate
route­
to­
route
extrapolation
should
be
performed
for
these
risk
assessments
(
i.
e.,
oral
to
dermal
components
use
absorption
rates
of
36
percent).

3.3
FQPA
Considerations
The
Hazard
Identification
Assessment
Review
Committee
(HIARC)
recommended
that
the
FQPA
safety
factor
be
removed
for
disulfoton
(A
Combined
Report
of
the
Hazard
Identification
Assessment
Review
Committee,
1/
19/
2000
and
the
FQPA
Safety
Factor
Committee,
1/
24/
2000).
The
toxicity
database
is
complete
including
neurotoxicity
studies
in
rats
and
there
is
no
evidence
of
either
neurotoxicity
or
increased
susceptibility
of
fetuses
or
offspring
in
prenatal
and
postnatal
studies
in
rabbits
or
rats.

The
committee
determined
that
the
1X
FQPA
factor
is
applicable
for
all
populations.
15
4.0
EXPOSURE
ASSESSMENT
4.1
Summary
of
Registered
Uses
Disulfoton
is
an
organophosphate
insecticide/
acaricide
registered
by
Bayer
Corporation
under
the
trade
name
DiSyston
®
.
Disulfoton
is
registered
in
the
United
States
for
preplant,
at­
planting,
preemergence
and
foliar
applications.
Formulations
include
the
98.5
percent
active
ingredient
(ai)
technical
product,
an
emulsifiable
concentrate
(17.5
percent
to
85
percent
ai),
and
a
granular
(0.37
percent
to
15
percent
ai).

Disulfoton
has
been
registered
for
use
on
both
occupational
and
non­
occupational
usesites
Occupational
use­
sites
include
food
and
feed
crops,
nut
trees,
non­
bearing
fruit
trees,
ornamental
flowers,
shrubs
and
trees,
and
potted
plants.
Non­
occupational
use­
sites
include
residential
ornamental
flowers,
shrubs
and
trees,
residential
rose
bushes,
residential
vegetable
gardens
(proposed
for
deletion),
and
residential
potted
plants.
Application
rates
range
widely
from
0.
005
lb
ai/
1000
ft
2
to
over
100
lb
ai/
A.
Disulfoton
is
applied
with
ground
and
air
equipment
as
well
as
hand­
held
equipment.

4.2
Dietary
Exposure
from
Food
The
Metabolism
Committee
concluded
that
residue
to
be
regulated
in
plants
include
parent
disulfoton
and
five
metabolite
expressed
as
disulfoton
(Table
5).

In
plants,
disulfoton
is
rapidly
converted
to
disulfoton
sulfoxide
and
sulfone
or
disulfoton
oxygen
analog
sulfoxide
and
sulfone
(demeton­
S
sulfone).
When
the
sulfur­
containing
side
chain
is
removed,
the
products
are
no
longer
cholinesterase
inhibitors.

In
ruminants
and
poultry,
of
the
six
metabolites
of
concern,
only
parent
disulfoton
was
identified.

The
analytical
methods
for
enforcement
and
data
collection
involve
oxidation
of
disulfoton
and
its
metabolites
to
the
corresponding
sulfones.
It
should
be
noted
the
method
of
analysis
for
USDA
Pesticide
Data
Program
(PDP)
and
the
Food
and
Drug
Administration
(FDA)
data
analyzes
for
disulfoton
and
each
metabolite
individually
where
analyzed
because
the
oxidation
step
is
not
included.
The
PDP
included
some
but
not
all
metabolites.

Tolerances
for
disulfoton
residues
in
food
were
reassessed
and
range
from
0.
01
ppm
for
milk
to
5.
0
ppm
for
oats
and
wheat
folder.
For
additional
details
see
Appendix
4.
16
Table
5:
Common
and
Chemical
Names
of
Identified
Disulfoton
Tolerance
Residues
I.
Disulfoton
IV.
Disulfoton
oxygen
analog;
Demeton­
S
O,
O­
diethyl
S­[
2­(
ethylthio)
ethyl]
phosphorodithioate
O,
O­
diethyl
S­[
2­(
ethylthio)­
ethyl]
phosphorothioate
II.
Disulfoton
sulfoxide
V.
Disulfoton
oxygen
analog
sulfoxide
O,
O­
diethyl
S­[
2
ethylsulfinyl)
ethyl]
phosphorodithioate
O,
O­
diethyl
S­[
2­(
ethylsulfinyl)
ethyl
phosphorothioate
III.
Disulfoton
sulfone
VI.
Disulfoton
oxygen
analog
sulfone
O,
O­
diethyl
S­[
2­(
ethylsulfonyl)
ethyl]

phosphorodithioate
O,
O­
diethyl
S­[
2­(
ethylsulfonyl
ethyl]
phosphorothioate
4.2.1
Acute
and
Chronic
Dietary
Exposure
Methodology
and
Characterization
The
acute
and
chronic
dietary
risk
assessments
are
performed
using
DEEM®
software.
The
dietary
exposure
estimates
are
the
most
refined
possible
from
the
data
available.
For
the
current
Tier
3
dietary
risk
estimates,
a
probabilistic
model
(Monte
Carlo)
was
used
for
acute
dietary
risk
and
deterministic
methodology
utilizing
average
food
consumption
was
used
for
chronic
dietary
risk.

USDA's
Pesticide
Data
Program
(PDP)
and
the
Food
and
Drug
Administration
(FDA)
data
were
used
for
detectable
levels
of
disulfoton
and
metabolites
of
concern.
PDP
and
FDA
collect
residue
data
on
large
food
samples
(generally
5
lb
or
more).
The
data
is
collected
in
a
statistically
sound
manner
and
under
Good
Laboratory
Practices
that
are
approved
by
the
Agency.

For
the
acute
dietary
assessment,
all
single
serving
food
forms
included
in
the
disulfoton
assessment,
and
for
which
monitoring
data
were
used
include
asparagus,
broccoli,
cabbage,
cauliflower,
sweet
corn,
head
lettuce,
leaf
lettuce,
sweet
peppers,
potatoes,
and
tomatoes.

Combining
½
LODs
for
disulfoton
and
its
five
metabolites
for
non­
detects
may
over
estimate
the
probable
levels
of
these
residues.
The
½
LOD
procedure
was
modified
to
include
½
LOD
for
parent
and
those
metabolites
that
were
likely
to
occur
(estimated
from
field
trial
and
metabolism
data
which
indicated
only
three
of
the
five
metabolites
were
likely
to
occur).
This
method
yields
conservative
estimates
of
the
possible
residue
levels,
and
will
not
underestimate
these
levels.
For
details
on
the
use
of
this
method
to
modify
the
use
of
½
LOD
for
disulfoton
and
all
five
metabolites
in
estimating
appropriate
values
for
non­
detectable
residues,
see
Monitoring
Data,
in
Appendix
4.

Percent
Crop
Treated
Data
17
A
quantitative
usage
analysis
was
provided
by
OPP's
Biological
and
Economic
Analysis
Division
(BEAD)
based
on
data
years
1987­
98
(Steven
M.
Nako,
QUA
date:
May
5,
1999).
Data
sources
included
USDA/
NASS
(1990­
97),
California
EPA,
Department
of
Pesticide
Regulation
(1993­
96),
National
Center
for
Food
and
Agricultural
Policy
(1992),
and
various
proprietary
data
sources
including
Doane
(1987­
98),
Maritz,
and
Mike
Buckley
(1994­
97).

Contribution
of
potential
residues
from
crops
with
import
tolerances
was
based
on
information
provided
by
Bayer
Corporation
(MRIDs
44821701
&
44821702).
As
a
default
assumption,
all
imports
from
countries
approved
for
disulfoton
use
on
coffee,
hops,
and
rice
were
included,
and
of
these
imports
100
percent
were
assumed
treated
with
disulfoton.
Additionally,
only
Argentina
has
a
registration
for
disulfoton
on
hops
but
in
the
submitted
analysis
100
percent
of
the
imported
hops
and
imported
beer
(from
all
countries)
was
considered
as
treated.
The
registrant's
proposal
for
these
crops
is
acceptable
and,
in
the
absence
of
more
refined
data,
will
be
used
in
estimating
residues
on
these
crops.

Food
Processing
Factors
The
registrant
has
included
processing
information
in
their
most
recent
refined
dietary
assessments
(explained
and
documented
in
MRIDs
44821701
&
44821702).
These
factors
were
based
on
several
Bayer
reports
as
well
as
published
articles
from
the
scientific
literature
and
were
used
by
Bayer
to
adjust
residue
values
derived
from
field
trial
data.
These
reports
have
been
reviewed
and,
where
applicable,
the
data
have
been
incorporated
in
the
dietary
risk
assessment.

4.2.2
Acute
Dietary
Risk
(Food)

The
most
highly
refined
acute
dietary
risk
using
available
data
is
presented
below
in
Table
6.
The
highest
acute
dietary
risk
is
9.
6
percent
of
the
aPAD
at
the
99.9
th
percentile
for
children
one
to
six
years
old.
The
acute
dietary
risk
for
the
general
population
is
seven
percent
of
the
aPAD
at
the
99.9
th
percentile.
See
table
6
for
the
acute
dietary
risk
for
other
subpopulations.

An
extensive
sensitivity
analysis
has
not
been
conducted;
however,
it
would
be
expected
that
the
critical
commodities
would
be
high
consumption
items
that
have
residues
on
them.
The
succulent
beans
have
the
most
delectable
residues
from
monitoring
data,
although
they
are
few
and
at
low
levels.
For
additional
details
see
Appendix
4.
18
Table
6:
Acute
Dietary
Risk
Estimates
(aPAD
=
0.0025
mg/
kg/
day)

Population
95
th
percentile
99
th
percentile
99.
9
th
percentile
Exposure
%
aPAD
Exposure
%
aPAD
Exposure
%
aPAD
US
pop­
All
seasons
0.000031
1.2
0.
000065
2.6
0.
000176
7.0
All
infants
(<
1
yr)
0.000043
1.7
0.
000074
3.0
0.
000218
8.7
Children
(1­
6
yr)
0.000063
2.5
0.
000116
4.6
0.
000239
9.6
Children
(7­
12
yr)
0.
000041
1.6
0.
000076
3.0
0.
000203
8.1
Females
(13+/
preg/
not
nursing)
0.000019
0.76
0.000033
1.3
0.
000084
3.4
Males
(20+
yr)
0.
000021
0.84
0.000046
1.8
0.
000148
5.9
Seniors
(55+)
0.
000019
0.78
0.000045
1.8
0.
000184
7.4
DEEM
®
(Ver
6.
78),
Acute
analysis
disulfoton
based
on
1989­
92
data.

4.2.3
Chronic
Dietary
Risk
(Food)

The
estimates
of
chronic
dietary
exposures
from
uses
of
disulfoton
on
food
and
feed
crops
are
shown
in
Table
7.
The
highest
chronic
food
exposure
was
to
children
one
to
six
years
old
at
3.5
percent
of
the
cPAD.
The
chronic
dietary
risk
for
the
general
population
is
2.
3
percent
of
the
cPAD.

For
chronic
dietary
risk
the
chronic
module
version
6.76
of
DEEM™
was
used
and
is
the
most
highly
refined
possible
with
the
data
available.
Human
consumption
of
the
various
commodities
was
estimated
from
the
1989
­
1992
USDA
Continuing
Surveys
of
Food
Intake
for
Individuals.
The
chronic
assessment
incorporated
average
residues
of
disulfoton
and
its
five
metabolites
of
concern
from
monitoring
data
and
field
trials,
adjusted
for
percent
crop
treated
and
for
residue
reduction
or
concentration
from
processing
and
cooking.
For
additional
details
see
Appendix
4.
19
Table
7:
Chronic
Dietary
Risk
Estimates
(cPAD
=
0.00013
mg/
kg/
day)

Population
Average
Exposure
(mg/
kg/
day)
%cPAD
US
population
(total)
0.000003
2.3
All
infants
(<
1
yr)
0.000001
0.9
Children
(1­
6
yr)
0.000005
3.5
Children
(7­
12
yr)
0.
000003
2.4
Females
(13­
19
not
preg
or
nursing)
0.
000002
1.4
Females
(20+
yr
not
preg
or
nursing)
0.
000003
2.3
Females
(13+
preg/
not
nursing)
0.
000002
1.3
Females
(13+
yr
nursing)
0.
000002
1.9
Males
(20+
yr)
0.
000003
2.4
Seniors
(55+)
0.
000003
2.5
DEEM
®
(Ver.
6.76)
Chronic
dietary
analysis
for
disulfoton
using
1989­
92
data;
Adjustment
factor
#2
used
4.3
Water
Exposure
(Drinking
Water
Sources)

Potential
exposure
to
disulfoton
in
drinking
water
was
assessed
using
modeling
and
limited
monitoring
data.
The
data
were
provided
by
the
Environmental
Fate
and
Effects
Division
(EFED)(
Memorandum
from
Kathryn
Montague,
John
Jordon,
James
Wolf,
and
Mary
Frankenberry
to
Christina
Scheltema,
SRRD
(amended
10/
07/
99
from
8/
26/
99).
The
major
routes
of
dissipation
are
microbial
degradation
in
an
aerobic
soil
and
aqueous
photolysis
and
soil
photolysis.
Limited
data
suggest
that
the
sulfoxide
and
sulfone
degradates
are
much
more
persistent
than
the
parent.

4.3.1
Surface
Water
A
Tier
2
assessment
was
conducted
using
PRZM/
EXAMS
modeling
based
on
the
fate
profile
for
disulfoton,
disulfoton
sulfoxide,
and
disulfoton
sulfone,
as
well
as
maximum
registered
application
rates.
The
maximum
peak
concentration
of
parent
disulfoton
and
cholinesterase
inhibiting
residues
was
estimated
at
58

g/
L
and
the
estimated
maximum
mean
of
annual
averages
is
9.3

g/
L.
20
4.3.2
Groundwater
The
SCI­
GROW
(Screening
Concentrating
in
Groundwater)
screening
model
was
used
to
estimate
potential
groundwater
concentrations
for
disulfoton
parent
and
residues.
At
the
maximum
application
rate,
the
maximum
predicted
disulfoton
and
residue
groundwater
concentration
was
3.2

g/
L
from
SCI­
GROWmodels.
Groundwater
levels
from
SCI­
GROW
are
supported
by
the
2.
9

g/
L
from
limited
monitoring
data
(see
Section
4.
4.
3).

4.3.3
Monitoring
Data
Surface
water
monitoring
data
collected
by
the
USGS
as
part
of
the
National
Water
Quality
Assessment
(NAWQA)
program
was
also
considered.
Disulfoton
and
residues
were
found
in
10
out
of
2700
surface
water
samples.
Maximum
concentrations
were
0.002

g/
L
and
0.007­
0.041

g/
L
in
integrated
streams/
agricultural
wells
and
urban/
agricultural
streams,
respectively.
There
were
no
reported
detections
in
about
2200
groundwater
samples.

EPA's
Pesticides
in
Groundwater
Data
Base
(GWDB)
(EPA
732­
12­
92­
0001,
1992)
and
EPA's
STORET
data
was
also
reviewed.
EPA's
GWDB
showed
no
detects
in
2430
wells
from
11
states
(limit
of
detection
was
0.
01
to
6.
0

g/
L).
However,
the
GWDB
data
showed
that
disulfoton
was
detected
in
six
of
12
wells
sampled
in
Virginia
(0.04
to
2.9

g/
L)
and
in14
of26
wells(
4.
0to100

g/
L)
sampled
in
Wisconsin.
The
data
from
Wisconsin
was
not
quantity
assured.
The
data
from
Virginia
and
Wisconsin
wells
show
the
potential
contamination
of
wells
in
vulnerable
areas
and
support
the
SCI­
GROW
modeling
data.

4.3.4
DWLOCs
for
Acute
and
Chronic
Exposure
The
Drinking
Water
Level
of
Comparison
(DWLOC)
is
the
concentration
of
a
pesticide
in
drinking
water
that
is
acceptable
as
a
theoretical
upper
limit,
in
light
of
total
aggregate
exposure
to
the
pesticide
from
food,
water,
and
residential
sources.
DWLOCs
have
been
calculated
for
acute
dietary
and
chronic
dietary
exposure.
For
assessing
human
health
risk,
DWLOCs
are
compared
to
estimated
environmental
concentrations
(EECs).
When
DWLOCs
are
greater
than
the
EECs,
the
aggregate
risk
from
food,
water,
and
residential
(if
applicable)
exposures
is
considered
to
be
less
than
the
Agency's
level
of
concern.
21
4.3.4.1
Acute
DWLOCs
The
acute
DWLOC
values
are
shown
in
Table
8
below.
The
highest
acutely
exposed
groups
from
food
are
children
one
to
six
years
old
and
non­
nursing
infants
less
than
one
year
old.
The
acute
drinking
water
estimated
concentration
for
surface
water
(58

g/
L)
was
greater
than
DWLOC
acute
for
children
one
to
six
years
and
infants
less
than
one
year
(23

g/
L).
This
indicates
that
acute
exposure
to
disulfoton
and
residues
in
surface
water
may
be
a
risk
concern.

Table
8:
DWLOC
Values
for
Total
Acute
Dietary
Exposure
at
the
99.9
th
percentile
(DWLOC
acute
)

Population
Acute
PAD
(mg/
kg/
day)
Food
Exposure
(mg/
kg/
day)
Max.
Water
Exposure
(mg/
kg/
day)
DWLOC
acute
(g/
L)
PRZM/
EXAMS
(g/
L
a
)
SCI­
GROW
(g/
L)

US
population
0.
00250
0.000176
0.00232
81
58
3.2
Infants
<1
yr/
non
nursing
0.00250
0.000237
0.00226
23
58
3.2
Children
1­
6
yr
0.00250
0.000239
0.00226
23
58
3.2
Female
(13+
yr/
nursing)
0.00250
0.000117
0.00238
70
58
3.2
Seniors
(55+
yr)
0.
00250
0.000184
0.00232
81
58
3.2
a
The
peak
water
levels
of
58
g
(disulfoton
and
cholinesterase
inhibiting
residues)/
L
from
Tier
2
PRZMZ3/
EXAMS
(1­
in­
10
year
values)
model,
page
15,
Table
3b
of
the
memorandum
cited
in
section
4.
4).

The
default
body
weights
and
water
consumption
values
used
to
calculate
DWLOCs
are
as
follows:
70
kg/
2L
(adult
male),
60
kg/
2L
(adult
female),
and
10
kg/
1L
(children/
infants).
According
to
the
August
1,
1999
Updated
Interim
Guidance
for
Incorporating
Water
Exposure
into
Aggregate
Risk
Assessments,
the
following
formulas
were
used
to
calculate
the
acute
DWLOCs.

DWLOC
acute
(ug
/
L)
day
water
exposure
(mg
/
kg
/
day)
body
weight
(kg)

Water
consumption
(L)
10
3
(mg
/
ug)
=
One 
×

×
 
Where;

One
­
day
water
exposure
(mg
/
kg
/
day)

Acute
foodexposure
(mg
/
kg
/
day)]
=
[aPAD 
22
4.3.4.2
Chronic
DWLOCs
The
chronic
DWLOC
values
are
shown
in
Table
9.
The
chronic
drinking
water
estimated
concentration
for
surface
water
(9.3

g/
L)
exceeds
the
DWLOCchronic
(1.
2
to
4.4

g/
L)
for
all
population
subgroups.
The
chronic
drinking
water
estimated
concentration
for
groundwater
(3.2

g/
L)
exceeds
the
DWLOCchronic
for
children
one
to
six
years
and
infants
less
than
one
year.
This
indicates
the
chronic
exposure
to
disulfoton
and
residues
in
drinking
water
may
be
a
risk
of
concern.

Table
9:
DWLOC
Values
for
Total
Chronic
Dietary
Exposure
(DWLOC
chronic
)

Population
Chronic
PAD
(mg/
kg/
day)
Food
Exposure
(mg/
kg/
day)
Max.
Water
Exposure
(mg/
kg/
day)
DWLOC
chronic
(g/
L)
PRZM/
EXAMS
(g/
L
a
)
SCI
GROW
(g/
L)

cPAD
0.000130
0
0.
000130
4.5
9.
3
3.2
US
Population
0.000130
0.000003
0.000127
4.4
9.
3
3.2
Infants
<1
yr
0.
000130
0.000001
0.000129
1.3
9.
3
3.2
Children
1­
6
yr
0.000130
0.000005
0.000125
1.2
9.
3
3.2
Female
(13+
yr)/
nursing
0.000130
0.000002
0.000128
3.8
9.
3
3.2
a
The
maximum
mean
of
annual
average
concentration
9.
3
g
(disulfoton
and
cholinesterase
inhibiting
residues)/
L
from
PRZM/
EXAMs
model,
tier
2
water
assessment
,
page
15,
Table
3b
of
the
memorandum
cited
in
section
4.
4.

Chronic
DWLOCs
are
calculated
from
chronic
dietary
(food)
exposure
and
default
body
weights
and
default
water
consumption.
According
to
the
August
1,
1999
Updated
Interim
Guidance
for
Incorporating
Water
Exposure
into
Aggregate
Risk
Assessments,
the
following
formulas
were
used
to
calculate
the
chronic
DWLOCs.

DWLOC
chronic
ug
L
Chronic
water
mg
kg
day
body
weight
kg
Water
consumption
L
(/)
(//)
()

()
(mg
/
ug)
=
×

×
 
exposure
10
3
Where;

Chronic
water
consumption
mg
kg
day
cPAD
Chronic
food
mg
kg
day
(//)

[(//)]
=
 
exposure
23
4.4
Occupational/
Residential
Exposure
An
occupational
exposure
assessment
is
required
for
an
active
ingredient
if
(1)
certain
toxicological
criteria
are
triggered
and
(2)
if
there
is
potential
exposure
to
handlers
(mixers,
loaders,
applicators,
etc.)
during
use
or
to
persons
entering
treated
sites
after
application
is
complete.
Disulfoton
meets
both
criteria.

Based
on
toxicological
NOAELs
and
potential
exposure
and
uses,
the
Agency
has
conducted
exposure
and
risk
assessments
for
occupational/
residential
handlers
and
postapplication
workers.
The
margin
of
exposure
(MOE),
calculated
for
each
occupational
exposure
scenario,
is
inclusive
of
total
exposure
(dermal
and
inhalation)
and
is
calculated
as
MOE
=
1/[(
1/
MOEdermal
)+(
1/
MOEinhalation
)].

4.4.1
Assumptions
for
Occupational
Handler
Exposure
An
exposure
assessment
for
each
exposure
scenario
is
developed
where
appropriate
data
are
available,
using
the
Pesticide
Handlers
Exposure
Database
(PHED)
Version
1.
1.
PHED
was
designed
by
a
task
force
of
representatives
from
U.
S.
EPA,
Health
Canada,
the
California
Department
of
Pesticide
Regulation
and
member
companies
of
the
American
Crop
Protection
Association.
PHED
is
a
software
system
consisting
of
two
parts—
a
database
of
measured
exposure
values
for
workers
involved
in
handling
of
pesticides
under
actual
field
conditions
and
a
set
of
computer
algorithms
used
to
subset
and
statistically
summarize
the
selected
data.
Currently,
the
database
contains
over
1,
700
monitored
individuals
(i.
e.,
replicates).
Users
select
criteria
to
subset
the
PHED
database
to
reflect
the
exposure
scenario
being
evaluated.
The
subsetting
algorithms
in
PHED
are
based
on
the
central
assumption
that
the
magnitude
of
the
handler
exposures
to
pesticides
are
primarily
a
function
of
activity
(e.
g.,
mixing/
loading,
applying),
formulation
type
(e.
g.,
liquids,
wettable
powders,
granulars),
application
method
(e.
g.,
aerial,
groundboom),
and
clothing
scenarios
(e.
g.,
gloves,
double
layer
clothing).
While
data
from
PHED
provide
the
best
available
information
on
handler
exposures,
it
should
be
noted
that
some
aspects
of
the
included
studies
(e.
g.,
duration,
acres
treated,
pounds
of
active
ingredient
handled)
may
not
accurately
represent
labeled
uses
in
all
cases.
HED
has
developed
a
series
of
tables
of
standard
unit
exposure
values
for
many
occupational
scenarios
that
can
be
utilized
to
ensure
consistency
in
exposure
assessments.
The
Revised
Occupational
and
Residential
Exposure
Assessment,
Appendix
6,
summarizes
the
caveats
and
parameters
specific
to
the
surrogate
data
used
for
each
scenario
and
corresponding
exposure/
risk
assessment
for
disulfoton.
Table
10
shows
the
range
of
MOEs
for
combined
dermal
and
inhalation
exposure.
The
range
of
the
MOE
in
each
scenario
in
Table
10
is
the
result
of
the
different
disulfoton
label
use
rates
possible
by
the
handler.
The
highest
MOE
and
the
lowest
MOE
in
Table
10,
respectively
represent
the
lowest
and
highest
labeled
use
rate
for
that
scenario.
24
Table
10:
Occupational
Handler
Total
Exposure
(dermal
and
inhalation)
to
Disulfoton
for
Short­
and
Intermediate­
Term
Exposure
with
Baseline,
PPE
or
Engineering
Controls
(EngC)

NOTE:
An
MOE<
100
exceeds
Agency's
Level
of
Concern.
See
Appendix
6
for
additional
detail
about
exposure
and
MOEs
Exposure
Scenario
(Scenario#)
Short­
Term
Exposure
MOE
Intermediate­
Term
Exposure
MOE
Baseline
PPE
EngC
Baseline
PPE
EngC
Mixer/
Loader
Risk
Mixing/
Loading
Liquid
Formulations
(Emulsifiable
Concentrates)
for
Aerial/
Chemigation
Application
(1a)
0.009­
0.06
1.4­
8.4
2.
9­
17
0.
002­
0.01
0.3­
1.9
0.6­
3.8
Mixing/
Loading
Liquid
Formulations
(Emulsifiable
Concentrates)
for
Ground­
boom
Application
(1b)
0.03­
0.2
4.
6­
37
9.
4­
75
0.
006­
0.05
1.0­
8.4
2.
1­
17
Mixing/
Loading
Liquid
Formulations
(Emulsifiable
Concentrates)
for
Orchard
Airblast
Sprayer
Application
(1c)
0.08
12
25
0.02
2.8
5.
6
Loading
Granulars
for
Aerial
Application
(2a)
1.7­
4.5
6.
2­
17
85­
230
0.7­
1.9
2.
1­
5.5
36­
95
Loading
Granulars
for
Drawn
Spreader
Application
(2b)
1.9
200
6.9­
200+
93­
1000
0.8­
84
2.3­
240
39­
440
Applicator
Risk
Applying
Sprays
with
a
Fixed­
Wing
Aircraft
(3)
No
data
See
EC
No
data
See
EngC
14­
29
No
data
See
EngC
No
data
See
EC
3.3­
6.5
Applying
Granulars
with
a
Fixed
Wing
Aircraft
(4)
No
data
See
EngC
No
data
See
EngC
3.0­
8.0
No
data
See
EngC
No
data
See
EngC
2.0­
5.4
Applying
Sprays
with
a
Helicopter
(5)
No
data
See
EngC
No
data
See
EngC
42­
84
No
data
See
EngC
No
data
See
EngC
8.8­
18
Applying
Granulars
with
a
Helicopter
(6)
No
data
No
data
No
data
No
data
No
data
No
data
Table
10:
Occupational
Handler
Total
Exposure
(dermal
and
inhalation)
to
Disulfoton
for
Short­
and
Intermediate­
Term
Exposure
with
Baseline,
PPE
or
Engineering
Controls
(EngC)

NOTE:
An
MOE<
100
exceeds
Agency's
Level
of
Concern.
See
Appendix
6
for
additional
detail
about
exposure
and
MOEs
Exposure
Scenario
(Scenario#)
Short­
Term
Exposure
MOE
Intermediate­
Term
Exposure
MOE
Baseline
PPE
EngC
Baseline
PPE
EngC
25
Applying
Sprays
with
a
Groundboom
(7)
4.3­
34
7.1­
57
16­
130
1.2­
9.5
1.
6­
13
3.
6­
29
Applying
Sprays
to
Orchards
with
an
Airblast
(8)
0.6
1.
0
1.6
0.
1
0.2
0.
4
Applying
Granulars
with
a
TractorDrawn
Spreader
(9)
2.1­
230
6.9­
77
11­
120
0.8­
80
2.0­
210
3.6­
41
Mixer/
Loader/
Applicator
Risk
Loading/
Applying
Granulars
Using
a
Belly
Grinder
(10)
0.3­
1.3
0.
2­
0.8
NA
0.07­
0.3
0.
04­
0.2
NA
Loading/
Applying
Granulars
with
a
Push­
Type
Granular
Spreader
(11)
0.05­
4.7
0.
2­
19
NA
0.
01­
1.0
0.
04­
4.0
NA
Loading/
Applying
Granulars
by
Hand,
witha
Spoon,
ShakerCan,
or
a
Measuring
Scoop
(12)
1.5
3.
8
NA
0.3
0.
8
NA
Applying
Ready­
to­
Use
Liquid
as
a
Seed
Treatment
(13)
No
data
No
data
No
data
No
data
No
data
No
data
Flagger
Risk
Flagging
Aerial
Spray
Applications
(14)
5.7­
11
7.5­
15
15­
30
1.4­
2.9
1.
6­
3.3
3.3­
6.6
Flagging
Aerial
Granular
Applications
(15)
9.7­
26
21­
55
9.9­
26
2.7­
7.2
5.
0­
16
3.
3­
8.9
26
Handler
exposure
assessments
are
completed
by
EPA
using
a
baseline
exposure
scenario
and,
if
required,
increasing
levels
of
risk
mitigation.
Progressively
more
methods
of
handler
protection
beyond
baseline
are
added
to
achieve
an
appropriate
margin
of
exposure
(MOE),
such
as
Personal
Protective
Equipment
(PPE)
and
engineering
controls
(EngC).
Adequate
worker
protection
was
not
always
achieved
by
any
type
of
protection.
The
baseline
scenarios
generally
represents
a
handler
wearing
long
pants,
a
long­
sleeved
shirt,
and
no
chemical­
resistant
gloves.
PPE
controls
include,
but
are
not
limited
to
chemical
resistant
gloves,
eye
protection,
dust
/mist
protection
or
respirator
and
extra
clothing.
EngC
include
closed
systems
(loading
and
packaging
and/
or
closed
tractor
cabs
or
cockpits)
and
other
means.

4.4.2
Occupational
Handler
Exposure
and
Characterization
The
Agency
has
identified
15
different
major
exposure
scenarios
during
mixing,
loading
and
applying
disulfoton
products
to
agricultural
crops
and
non­
agricultural
sites.
The
accepted
range
of
application
equipment
and
methods
are
covered
in
Appendix
6,
in
addition
to
the
duration
of
handler
exposure.
The
duration
of
exposure
is
covered
by
short­
term
(one
day
to
one
week),
and
intermediate­
term
(one
week
to
several
months)
exposure
scenarios.
Disulfoton
products
are
typically
applied
one
to
three
times
per
season
and
at
20
to
42
day
intervals.

The
major
routes
of
exposure
to
handlers
are
dermal
and
inhalation.
The
margins
of
exposure
(MOE)
are
the
ratio
of
the
NOAELs
to
the
exposure.
MOEs
are
calculated
for
short­
term
and
intermediate­
term
dermal
and
inhalation
exposure
and
presented
in
Table
10
as
combined
MOEs
for
dermal
and
inhalation.
Shortterm
and
intermediate­
term
endpoints
are
presented
in
Section
3.
2.
There
were
no
long­
term
occupational
exposure
scenarios.
(See
Appendix
6
for
additional
detail.)

4.4.3
Occupational
Handler
Risks
of
Concern
The
acceptable
occupational
scenarios
(MOE>
100)
given
below
are
for
short­
term
and
intermediate­
term
exposure
each
with
baseline
and
PPE
protection
and
engineering
controls
in
place.
Most
occupational
scenarios
exceed
the
Agency's
level
of
concern
(MOE<
100).
Of
the
18
short­
term
and
intermediate­
term
exposure
scenarios
(dermal
and
inhalation
combined)
listed
in
Table
10,
10
show
marginally
low
MOEs
between
70
and
100.
For
individual
dermal
MOEs
and
inhalation
MOEs
see
Appendix
6.
All
occupational
scenarios
exceed
the
Agency's
level
of
concern,
except
those
listed
below.
27
Calculations
indicate
that
none
of
the
total
short­
term
MOEs
are
greater
than
100
for
baseline
protection
exposure
scenarios
except
the
following:


(2b)
loading
granulars
with
a
tractor­
drawn
spreader
to
nut
(pecan)
trees
assuming
an
application
rate
of
3
lb
ai/
A,
applied
to
2
acres
per
day.


(9)
applying
granulars
with
a
tractor­
drawn
spreader
to
nut
(pecan)
trees
assuming
an
application
rate
of
3
lb
ai/
A,
applied
to
2
acres
per
day.

Calculations
indicate
that
none
of
the
total
intermediate­
term
MOEs
are
greater
than
100
for
baseline
protection
exposure
scenarios.

Calculations
indicate
that
none
of
the
remaining
total
short­
term
MOEs
are
greater
than
100
with
additional
PPE.

Calculations
indicate
that
none
of
the
total
intermediate
­term
MOEs
are
greater
than
100
with
additional
PPE
except
the
following:


(2b)
loading
granulars
with
a
tractor­
drawn
spreader
to
nut
(pecan)
trees
assuming
an
application
rate
of
3
lb
ai/
A,
applied
to
2
acres
per
day.


(9)
applying
granulars
with
a
tractor­
drawn
spreader
to
nut
(pecan)
trees
assuming
an
application
rate
of
3
lb
ai/
A,
applied
to
2
acres
per
day.

Calculations
indicate
that
none
of
the
total
short­
term
MOEs
are
greater
than
100
for
scenarios
with
engineering
controls
in
place
except
the
following:


(2a)
loading
granulars
for
aerial
application
using
a
1.
0
lb
ai/
A
or
less
application
rate.


(2b)
loading
granulars
for
tractor­
drawn
spreader
application
to
agricultural
crops
at
application
rates
of
4
lb
ai/
A
or
less.
MOEs
are
greater
than
100
also
for
loading
of
granulars
for
application
to
non­
bearing
fruit
trees
and
to
flowers
and
groundcovers
using
a
tractor­
drawn
spreader.


(7)
applying
with
a
groundboom
to
agricultural
crops
using
an
application
rate
of
0.
5
lb
ai/
A.
28

(9)
applying
granulars
with
a
tractor­
drawn
spreader
to
agricultural
crops
at
0.
75
lb
ai/
A
and
to
flowers
and
groundcover
using
an
application
rate
of
28.6
lb
ai/
A.

Calculations
indicate
that
none
of
the
total
intermediate­
term
MOEs
are
greater
than
100
for
scenarios
with
engineering
controls
in
place
except
the
following:


(2b)
loading
granulars
for
tractor­
drawn
spreader
application
to
agricultural
crops
at
application
rate
of
1
lb
ai/
A
or
less.
MOEs
are
greater
than
100
also
for
loading
of
granulars
for
application
to
non­
bearing
fruit
trees
and
to
flowers
and
groundcovers
using
a
tractor­
drawn
spreader.

4.4.4
Data
Gaps
As
noted
below,
several
of
the
exposure
scenarios
could
not
be
assessed
due
to
lack
of
PHED
surrogate
data.
Data
gaps
exist
for
the
following
scenario:


(6)
­
no
PHED
data
exist
for
applying
granulars
from
helicopters.


(16)
­
no
PHED
data
exist
for
applying
ready­
to­
use
liquid
as
a
seed
treatment.

4.4.5
Data
Quality
and
Confidence
in
Assessment
Several
issues
must
be
considered
when
interpreting
the
occupational
exposure
risk
assessment.
Confidence
in
the
exposure
data
is
also
listed
in
Appendix
6,
as
low
(L),
medium
(M)
or
high
(H).
These
include:


Several
handler
assessments
were
completed
using
"low
quality"
PHED
data
due
to
the
lack
of
a
more
acceptable
data
set.


Several
generic
protection
factors
were
used
to
calculate
handler
exposures.
These
protection
factors
have
not
been
completely
evaluated
and
accepted
by
HED.


Factors
used
to
calculate
daily
exposures
to
handlers
(e.
g.,
acres
treated
per
day
and
gallons
of
liquid
applied)
are
based
on
the
best
professional
judgement,
due
to
a
lack
of
pertinent
use
data.
29
4.4.6
Postapplication
Exposure
Postapplication
exposure
potential
occurs
to
individuals
entering
treated
areas
for
harvesting
nut
trees
(pecans);
harvesting
low­
growing
field
crops;
weeding
and
scouting
and
other
non­
harvesting
activities
associated
with
low­
growing
crops;
and
transplanting,
harvesting
and
pruning
ornamentals.
EPA
estimates
that
a
48­
hour
reentry
interval
(REI),
based
on
the
acute
toxicity
category
(I),
and
is
adequate
to
protect
field
workers
when
4.0
lb
ai/
A
or
less
has
been
applied
as
a
disulfoton
spray
or
granules
to
the
field.
For
use
rates
that
exceed
4.0
lb
ai
/A,
minimum
reentry
times
of
28
to
36
days
are
estimated
using
standard
values
(Table
11).
The
assumptions
made
would
be
expected
to
bracket
the
reentry
exposure
levels
from
disulfoton
used
on
these
crops.

This
consideration
is
based
on
the
following:
(1)
Use
of
high
rates
directly
on
soil
and
that
often
soil
incorporated
(either
mechanically
or
by
watering
in)
occurs
and
that
high
application
rates
may
be
rarely
used
and
(2)
the
use
of
a
residue
fraction
that
is
retained
on
the
foliage
and
available
for
transfer
is
likely
to
be
substantially
less
than
the
20
percent
used.
Additional
data
are
required
to
further
refine
the
post
application
exposure
assessment.

Based
on
these
activities,
four
representative
scenarios
were
evaluated
using
surrogate
dislodgeable
foliar
residue
data
and
assumptions
about
transfer
of
residues
to
skin.
The
surrogate
assessments
presented
in
Table
11
are
based
on
the
applications
rates
on
disulfoton
labels
that
are
recommended
for
field
crops,
nut
trees
and
ornamentals.

Additional
details,
default
assumptions
and
formulas
for
the
calculations
for
the
dislodgeable
foliar
residues
and
reentry
times
are
presented
in
Appendix
6.

Table
11:
Disulfoton
Intermediate­
Term
Surrogate
Occupational
Postapplication
Assessment
(Range
Finder)
for
high
Application
Rates
Application
Rate
(lb
ai
/A)
DAT
a
DFR
(g/
cm
2
)
b
Dermal
Dose
(mg/
kg/
day)
MOE
8
28
0.
006
0.0002
130
28.6
32
0.
006
0.0003
110
102
36
0.0007
0.0003
100
a
DAT
is
"days
after
treatment."
b
Initial
DFR
=
Application
rate
x
Conversion
factor
(lb
ai/
A
=
11.
209
g/
cm
2
)
x
fraction
of
initial
ai
retained
on
foliage.
30
4.4.7
Human
Incidence
Information
Human
incidence
data
contained
in
a
memorandum
from
Jerome
Blondell
to
Jonathan
Becker
of
HED
(3/
25/
1998),
Review
of
Disulfoton
Incidence
Reports,
show
that
disulfoton
was
11
th
among
the
28
pesticides
reported
(1982­
1989)
with
the
highest
incidence
rates
and
had
the
highest
ratio
for
cases
when
the
pesticide
was
considered
the
primary
cause
of
poisoning
of
field
workers
per
1000
applications.
Disulfoton
ranked
third
on
percentage
of
occupational
Poison
Control
Center
cases
requiring
hospitalization
and
fourth
among
these
28
pesticides
studied
on
percentage
of
occupational
cases
with
life­
threatening
symptoms.
Death
(including
suicides
and
possible
homicides)
confounded
by
misuse
is
known
to
infrequently
occur;
however,
no
other
permanent
disability
has
been
adequately
documented.
The
report
does
not
indicate
the
frequency
or
proportion
of
incidences
related
to
morbidity,
to
labeled
uses,
or
misuse.

4.5
Residential
Exposure
4.5.1
Handler
Disulfoton
is
applied
one
to
three
times
per
season
and
thus
individual
handlers
would
mostly
be
exposed
short­
term.
Short­
term
exposure
scenarios
were
used
to
calculated
anticipated
residential
exposure
(Table
12).
Although
short­
term
exposure
is
defined
as
one
day
to
one
week,
the
dermal
and
inhalation
toxicity
data
used
in
the
calculations
covers
up
to
three
weeks
of
daily
exposure
and
is
considered
a
conservative
estimate
of
residential
exposure.
An
MOE
of
100
or
greater
is
below
the
Agency's
level
of
concern
for
residential
exposure.
Exposure
to
granular
formulations
were
evaluated,
since
only
granular
formulations
are
recommended
for
residential
use.

The
residential
risk
was
shown
to
range
from
MOEs
of
0.
002
to
1,900
(Table
12).
Only
two
types
of
activities
had
MOEs
below
the
Agency's
level
of
concern
for
the
lowest
application
rates
only,
and
these
were:
(1)
loading
/applying
granulars
with
a
push
type
spreader
to
flower
gardens
at
the
lower
rates
of
0.005
lb
ai/
1,
000
ft
2
(MOE=
1,900),
and
(2)
using
the
same
type
of
equipment
at
the
lowest
rate
of
0.00032
lb
ai/
4
ft
shrub
(MOE=
1,200).
Two
other
activities
show
marginally
low
MOEs.
These
were
(1)
loading
/applying
granulars
with
a
push
type
spreader
to
flower
gardens
at
the
lower
rates
of
0.1
lb
ai/
1,000
ft
2
(MOE=
93),
and
loading
and
applying
granulars
with
a
push
type
spreader
at
the
labeled
use
rate
of
0.
00188
lb
ai/
bush
to
50
rose
bushes
(MOE=
99).
All
other
residential
activities
showed
MOEs
ranging
from
0.
002
to
37
(Table
12).
Table
12
lists
MOEs
for
dermal
and
inhalation
exposure
combined.
For
individual
dermal
MOEs
and
inhalation
MOEs
see
Appendix
6.

The
anticipated
residential
use
patterns
and
current
labeling
indicate
several
major
31
exposure
scenarios
based
on
the
types
of
equipment
that
potentially
can
be
used
to
make
disulfoton
applications.
These
scenarios
include:
(1)
loading/
applying
granulars
with
a
belly
grinder;
(2)
loading/
applying
granulars
with
a
push
type
spreader;
(3)
loading/
applying
granulars
with
a
spoon,
shaker
can,
measuring
scoop,
or
by
hand;
(4)
application
of
insecticidal
spikes.

4.5.2
Residential
Handler
Exposure
Scenarios­
Data
and
Assumptions
Residential
handler
exposure
assessments
were
completed
by
HED
using
a
baseline
exposure
scenario.
PHED
values
used
to
estimate
daily
unit
exposure
were
taken
from
Standard
Operating
Procedures
(SOPs)
for
Residential
Exposure
Assessments,
document
dated
December
1997.
The
caveats
and
parameters
specific
to
surrogate
data
used
for
each
scenario
and
corresponding
exposure/
risk
assessment
are
detailed
in
Appendix
6.

Data
Quality
The
quality
of
the
data
used
in
the
residential
and
non­
occupational
risk
assessment
is
ranked
of
low
confidence
category
for
push
type
granular
spreaders.
Factors
used
to
calculate
daily
exposures
to
handlers
(e.
g.,
square
footage
treated
per
day,
number
of
pots
treated
per
day
and
number
of
tree
or
shrubs
treated
per
day)
are
best
professional
judgement
due
to
a
lack
of
pertinent
data.

Data
Gaps
No
satisfactory
data
exists
for
applying
insecticidal
spikes
to
roses
or
ornamental
shrubs
and
trees.
32
Table
12:
Residential
Handler
Short­
term
Risks
from
Disulfoton
at
Baseline
Exposure
Scenario
(Scenario
#)
Crop
Type
or
Target
a
Amount
Handled
Per
Day
b
Application
Rate
Baseline
Total
Short­
Term
MOE
c
Mixer/
Loader/
Applicator
Risks
Loading/
Applying
Granulars
with
a
Belly
Grinder
(1)
Flower/
Veg
Gardens
(pre­
planting)
10,000
ft.
2
0.2
lb
ai/
1000
ft
2
0.1
0.1
lb
ai/
1000
ft
2
0.3
Loading/
Applying
Granulars
with
a
Push
Type
Spreader
(2)
Roses
50
bushes
0.
00188
lb
ai/
bush
99
Vegetable
Gardens
10,000
ft.
2
0.1125
lb
ai/
1,
000
ft
2
h
8.2
0.0313
lb
ai/
1,
000
ft
2
h
30
Flower
Gardens
1,000
ft.
2
0.3
lb
ai/
1,
000
ft
2
31
0.1
lb
ai/
1,
000
ft
2
93
0.005
lb
ai/
1,
000
ft
2
1,900
Ornamental
Shrubs/
Small
Trees
25
shrubs
1.32
lb
ai/
4
ft.
shrub
0.3
0.01
lb
ai/
4
ft.
shrub
37
0.00032
lb
ai/
4
ft.
shrub
1,200
Loading/
Applying
Granulars
with
a
Spoon,
Shaker
Can,
Measuring
Scoop,
or
by
Hand
(3)
Roses
50
bushes
0.
00188
lb
ai/
bush
0.
7
Vegetable
Gardens
10,000
ft.
2
0.1125
lb
ai/
1,
000
ft
2
h
0.06
0.0313
lb
ai/
1,
000
ft
2
h
0.2
Flower
Gardens
1,000
ft.
2
0.3
lb
ai/
1,
000
ft
2
0.2
0.1
lb
ai/
1,
000
ft
2
0.6
0.005
lb
ai/
1,
000
ft
2
13
1.32
lb
ai/
4
ft.
shrub
0.002
Ornamental
Shrubs/
Small
Trees
25
shrubs
0.01
lb
ai/
4
ft.
shrub
0.3
0.00032
lb
ai/
4
ft.
shrub
8.1
Potted
Plants
20
pots
0.
00011
lb
ai/
6"
pot
29
Table
12:
Residential
Handler
Short­
term
Risks
from
Disulfoton
at
Baseline
Exposure
Scenario
(Scenario
#)
Crop
Type
or
Target
a
Amount
Handled
Per
Day
b
Application
Rate
Baseline
Total
Short­
Term
MOE
c
33
Application
of
Insecticidal
Spikes
(4)
Roses/
Trees
No
Data
No
Data
No
Data
a
Crop
Type
or
Target
provides
a
general
description
of
the
intended
use
of
various
products
containing
disulfoton.
Separate
categories
are
presented
because
of
the
distinct
differences
in
application
rates
and
acres
treated.
b
Amount
Handled
Per
Day
values
are
from
default
estimates
of
square
footage
or
number
of
pots
treated
a
single
day
for
each
exposure
scenario
of
concern.
c
Total
Short­
term
MOE
=
1/
[(
1/
Short­
term
Dermal
MOE)
+
(1/
Short­
term
Inhalation
MOE)].

4.5.3
Postapplication
Residential
Exposure
and
Risk
Potential
postapplication
exposure
from
residential
use
of
the
granular
product
can
occur
during
transplanting
garden
or
house
plants,
and
weeding
treated
flowers,
ornamental
shrubs,
and
trees.
Potential
exposure
can
occur
from
non­
harvest
activities
such
as
weeding
home
vegetables,
and
from
incidental
soil
ingestion
by
toddlers
(hand­
to­
mouth
exposure).

The
Agency
has
no
data
upon
which
to
assess
postapplication
contact
with
treated
soil
through
activities
such
as
weeding,
hoeing,
and
transplanting
home
ornamentals,
vegetable
crops,
and
house
plants.
However,
postapplication
risks
for
adult
homeowners
were
estimated
to
be
low.

Exposure
to
toddlers
was
assessed
using
surrogate
data.
Exposure
to
toddlers
(hand­
to­
mouth)
in
treated
vegetable
and
flower
gardens
at
the
maximum
application
rates
for
these
scenarios
show
MOEs
of
230
and
610,
respectively.
Lower
rates
of
application
would
show
even
higher
MOEs.
No
data
were
available
to
assess
exposure
to
toddlers
(hand­
to­
mouth)
for
shrubs
and
small
tree
areas
treated
with
disulfoton
by
residential
handlers.

In
calculating
postapplication
toddler
exposure,
the
intermediate­
term
NOAEL
of
0.03
mg/
kg/
day
was
used
rather
than
short­
term
NOAEL
of
0.4
mg/
kg/
day
because
some
reentry
activity
was
considered
to
be
longer
than
one
to
seven
days
and
to
be
conservative.
The
MOE
for
toddlers
ingesting
soil
at
vegetable
and
flower
garden
application
sites
(at
the
lowest
application
rate)
showed
an
acceptable
MOE
greater
than
100.
3
Since
the
PRZM/
EXAMS
model
estimates
are
greater
than
the
SCI­
GROW
model
estimates,
DWLOCs
are
compared
to
the
PRZM/
EXAMS
estimates
only.

34
4.5.4
Potential
Spray
Drift
This
assessment
reflects
the
Agency's
current
approaches
for
completing
residential
exposure
assessments
based
on
the
guidance
provided
in
the
Draft:
Series
875­
Occupational
and
Residential
Exposure
Test
Guidelines,
Group
BPostapplication
Exposure
Monitoring
Test
Guidelines
(7/
24/
97
Version),
the
Draft:
Standard
Operating
Procedures
(SOPs)
for
Residential
Exposure
Assessment
(12/
11/
97
Version),
andtheOverview
of
Issues
Related
to
the
Standard
Operating
Procedures
for
Residential
Exposure
Assessment
presented
at
the
September
1999
meeting
of
the
FIFRA
Scientific
Advisory
Panel
(SAP).
The
Agency
is,
however,
currently
in
the
process
of
revising
its
guidance
for
completing
these
types
of
assessments
and
expanding
the
scope
of
the
residential
exposure
assessments
by
developing
guidance
for
characterizing
exposures
from
other
sources
already
not
included
such
as
from
spray
drift,
residential
residue
track­
in,
exposures
to
farm
worker
children,
and
exposures
to
children
in
schools.
Modifications
to
this
assessment
for
disulfoton
shall
be
incorporated
as
updated
guidance
becomes
available
and
it
is
feasible
from
a
regulatory
perspective.

5.0
AGGREGATE
RISK
(FOOD,
WATER
AND
RESIDENTIAL)

The
Food
Quality
Protection
Act
amendments
to
the
Federal
Food,
Drug,
and
Cosmetic
Act
(FFDCA,
Section
408(
b)(
2)(
A)(
ii))
require
for
establishing
a
pesticide
tolerance
"that
there
is
reasonable
certainty
that
no
harm
will
result
from
aggregate
exposure
to
pesticide
chemical
residue,
including
all
anticipated
dietary
exposures
and
other
exposures
for
which
there
is
reliable
information."
Aggregate
exposure
will
typically
include
exposures
from
food,
drinking
water,
and
residential
uses
of
a
pesticide.

The
aggregate
risk
estimate
to
disulfoton
has
addressed
exposure
from
dietary
(food)
sources,
drinking
water,
and
residential
uses.
Acute
and
chronic
dietary
food
risks
are
below
the
Agency's
level
of
concern
(<
100
percent
aPAD/
cPAD).
All
of
the
residential
use
scenarios
specified
on
the
label
exceed
the
Agency's
level
of
concern
(i.
e.,
MOE<
100)
at
the
maximum
application
rate,
except
for
roses
which
are
at
the
level
of
concern/
no
concern
(MOE=
99).
PRZM/
EXAMS
estimates
3
of
exposure
to
disulfoton
in
surface
water
exceed
the
Agency's
level
of
concern
(i.
e.,
DWLOCs<
EECs).
Therefore,
any
aggregation
of
exposure
from
residential
uses
and
drinking
water
with
food
exposure
would
only
further
increase
the
risk
even
higher
than
the
Agency's
level
of
concern.
35
6.0
ENDOCRINE
MODULATION
The
Food
Quality
Protection
Act
requires
that
EPA
develop
a
screening
program
to
determine
whether
certain
substances
(including
all
pesticides
and
inerts)
"may
have
an
effect
in
humans
that
is
similar
to
an
effect
produced
by
a
naturally
occurring
estrogen,
or
such
other
endocrine
effect...."
EPA
has
been
working
with
interested
stakeholders,
including
other
government
agencies,
public
interest
groups,
industry
and
research
scientists
to
develop
a
screening
and
testing
program
as
well
as
a
priority
setting
scheme
to
implement
this
program.
The
Agency's
proposed
Endocrine
Disrupter
Screening
Program
was
published
in
the
Federal
Register
of
December
28,
1998
(6
3
FR
71541).
The
Program
uses
a
tiered
approach
and
anticipates
issuing
a
Priority
List
of
chemicals
and
mixtures
for
Tier
1
screening
in
the
year
2000.
As
the
Agency
proceeds
with
implementation
of
this
program,
further
testing
of
disulfoton
and
its
end­
use
products
for
endocrine
effects
may
be
required.

7.0
CUMULATIVE
EXPOSURE
AND
RISK
It
has
been
determined
that
organophosphates
(OPs)
share
a
common
mechanism
of
inhibiting
cholinesterase.
As
required
by
FQPA,
cumulative
assessment
will
need
to
be
conducted
to
evaluate
the
risk
from
food,
water
and
non­
occupational
exposure
resulting
from
all
uses
of
organophosphates.
The
Agency
is
in
the
process
of
formulating
guidance
for
conducting
cumulative
risk
assessments.
When
the
guidance
is
finalized,
disulfoton
and
other
ChE­
inhibiting
compounds
(carbamates
and
organophosphates)
will
be
revisited
to
assess
the
cumulative
effects
of
exposure
to
multiple
cholinesterase
inhibiting
compounds.
36
8.0
REQUIRED
DATA
The
only
toxicity
study
required
is
from
a
general
data­
call­
in
for
a
developmental
neurotoxicity
study
(Guideline#
870.6300),
for
which
disulfoton
was
included.
There
are
requirements
for
product
chemistry
and
several
for
tolerance
assessments
and
recommendations
for
tolerance
revocation
(See
the
Appendix
5:
Residue
Chemistry
Considerations
for
the
Disulfoton
RED).

Data
needs
for
Product
Chemistry:


Guideline
#830.1750
for
EPA
Reg.
No.
3125­
183

Guideline
#830.1800
for
EPA
Reg.
No.
3125­
183

Guideline
#830.7050
for
EPA
Reg.
No.
3125­
183

Guideline
#830.1800
for
EPA
Reg.
No.
3125­
158

Guideline
#830.1800
for
EPA
Reg.
No.
3125­
128
Additional
data
needs
for
residue
chemistry
are
listed
in
Appendix
5.

Data
needs
for
Occupational
Assessment:

Occupational
exposure
data
is
necessary
for
applying
granulars
from
helicopters
and
for
applying
ready­
to­
use
liquid
as
a
seed
treatment
because
no
PHED
data
exist
for
these
scenarios.
In
addition,
the
Agency
has
no
data
on
exposure
from
the
use
of
disulfoton
spikes
for
tree
treatment.

9.0
CODEX
The
Codex
MRLs
are
expressed
in
terms
of
the
sum
of
disulfoton,
demeton­
S,
and
their
sulfoxides
and
sulfones
expressed
as
disulfoton.
Some
US
tolerance
are
still
expressed
in
terms
of
demeton­
S.
However,
since
the
molecular
weight
of
disulfoton
is
only
six
percent
lower
than
demeton­
S,
the
difference
is
small.
Codex
MRLs
and
the
U.
S.
tolerances
will
be
compatible
when
the
U.
S.
tolerance
expression
is
revised
to
include
disulfoton,
its
oxygen
analog,
and
their
sulfoxides
and
sulfones,
calculated
as
disulfoton.
37
10.0
APPENDICES
Appendix
1:
Toxicology
Chapter
for
the
Disulfoton
RED
(David
G.
Anderson)

Appendix
2:
The
Hazard
Identification
Assessment
Review
Committee
Report
for
Disulfoton
(Revisit)
(David
G.
Anderson).

Appendix
3:
The
FQPA
Safety
Factor
Committee
Report
on
Disulfoton
(Brenda
Tarplee).

Appendix
4:
The
Revised
Disulfoton:
Acute
and
Chronic
Dietary
Risk
Assessment
(Includes
MRID
#
44821701
&
44821702,
Chem.
No.
032501;
William
O.
Smith)

Appendix
5:
Product
Chemistry
and
Residue
Chemistry
Chapters
for
the
Disulfoton
RED
(John
Abbots/
Ken
Dockter)

Appendix
6:
Occupational/
Residential
Exposure
Chapter
for
the
Disulfoton
RED
(Jonathan
Becker)
and
Memorandum
from
Jerome
Blondell
to
Jonathan
Becker
of
HED
(3/
25/
1998):
Review
of
Disulfoton
Incidence
Reports
(Jerome
Blondell)