Document ID: EPA-HQ-OPP-2002-0302-0016
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-06-30T04:00Z

Page
1
of
151
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
June
22,
2006
MEMORANDUM
SUBJECT:
Dichlorvos
(
DDVP)
HED
Chapter
of
the
Reregistration
Eligibility
Decision
Document
(
RED).
PC
Code:
084001,
Case
#:
0310,
DP
Barcode:
D330262
Regulatory
Action:
Phase
5
Reregistration
Risk
Assessment
Type:
Single
Chemical/
Aggregate
FROM:
Susan
V.
Hummel,
Chemist,
Branch
Senior
Scientist
Reregistration
Branch
IV
Health
Effects
Division
(
7509C)

and
William
Dykstra,
Ph.
D.,
Toxicologist
David
Hrdy,
Biologist
David
Jaquith,
Industrial
Hygienist
Reregistration
Branch
IV
Health
Effects
Division
(
7509C)

THROUGH:
Ray
Kent,
Ph.
D.,
Branch
Chief
Reregistration
Branch
IV
Health
Effects
Division
(
7509C)

TO:
Eric
Olson,
CRM
#
61
Special
Review
Branch
Special
Review
and
Reregistration
Division
(
7508C)

Attached
please
find
the
revised
Human
Health
Risk
Assessment
for
dichlorvos
(
DDVP).
The
Risk
Assessment
uses
some
endpoints
based
on
human
studies,
found
to
be
in
compliance
with
the
human
studies
rule.
This
document
has
been
revised
to
address
error
only
comments
provided
by
the
registrant
(
AMVAC).
Additionally,
on
May
9,
2006,
AMVAC
requested
voluntary
cancellation
and/
or
amendments,
through
incorporation
of
terms
and
conditions
to
current
dichlorvos
registrations.
These
modifications
are
summarized
below:
Page
2
of
151
Voluntary
deletion
of
the
following:
Product
Types
1.
100
gram
(
g)
pest
strip
2.
21
g
pest
strip
(
contingent
on
the
granting
of
registration
for
16
g
pest
strip)
3.
Total
release
fogger
Use
Patterns
4.
Lawn,
Turf,
and
Ornamentals
5.
Crack
and
Crevice
Application
Method
6.
Mushroom
house
hand
held
fogger
7.
Greenhouse
hand
held
fogger
8.
Warehouse
hand
held
fogger
Label
Amendments
Occupational
Exposure
­­
Applicators
1.
Mushroom
house
Hose
End
Sprayer
­­
add
coveralls
to
personal
protective
equipment
requirements.
Occupational
­­
Post
Application
2.
Mushroom
houses
 
18
hour
re­
entry
interval
(
REI)
3.
Greenhouse
­­
12
hour
REI
Pest
Strips
Registrant
will
split
its
end
use
registrations
so
that
there
will
be
one
end
use
label
for
the
large
pest
strips
(
65
g
&
80
g)
and
another
for
the
small
pest
strips
(
10.5
g,
5.25
g,
and
a
new
16
g)
65
and
80
g
pest
strips
Label
language
to
read:
"
For
use
in
unoccupied
areas;
not
for
use
in
homes
except
garages,
attics,
crawl
spaces,
and
sheds
occupied
for
less
than
4
hours
per
day.

Also
for
use
in
boathouses,
museum
collections,
animal
buildings,
and
milk
rooms,
or
enclosed
areas
thereof,
occupied
for
less
than
4
hours
per
day.

For
use
in
unoccupied
areas
such
as
trash
dumpsters,
catch
basins,
bulk
raw
grain
bins,
storage
bins,
insect
traps,
enclosed
utility
boxes,
and
storage
units.
Also
for
use
in
non­
perishable
packaged
and
bagged
and
bulk
stored
processed
and
raw
agricultural
commodities
(
including
soybeans,
corn,
grains,
cocoa
beans
and
peanuts).

Also
for
use
in
the
following
unoccupied
structures,
provided
they
are
unoccupied
for
more
than
4
months
immediately
following
placement
of
a
pest
strip:
vacation
homes,
cabins,
mobile
homes,
boats,
farm
houses,
and
ranch
houses."

16
g
(
new),
10.5
g,
5.25
g
pest
strips
Label
language
to
read:

"
Within
homes,
use
only
in
closets,
wardrobes,
and
cupboards.
Also
for
use
in
storage
units,
garages,
attics,
crawl
spaces,
boathouses,
museum
collections,
garbage
cans,
trash
dumpsters,
animal
buildings,
milk
rooms,
catch
basins,
bulk
raw
grain,
and
storage
bins."
Page
3
of
151
Table
of
Contents
1.0
Executive
Summary
...........................................................................................................
5
1.1
Use
and
Major
Formulations
..................................................................................
5
1.2
Regulatory
History
..................................................................................................
5
1.3
Hazard
Identification
and
Dose­
Response
Assessment
.........................................
7
1.4
Exposure/
Risk
Assessment
and
Risk
Characterization.........................................
8
1.5
Human
Studies
.....................................................................................................
10
2.0
Ingredient
Profile
.............................................................................................................
10
2.1
Summary
of
Registered/
Proposed
Uses...........................................................
11
2.2
Structure
and
Nomenclature
...........................................................................
31
2.3
Physical
and
Chemical
Properties
...................................................................
31
3.0
Metabolism
Assessment
...................................................................................................
33
3.1
Comparative
Metabolic
Profile
.......................................................................
33
3.2
Nature
of
the
Residue
in
Foods
.......................................................................
33
3.2.1.
Description
of
Primary
Crop
Metabolism..........................................
33
3.2.2
Description
of
Livestock
Metabolism
..................................................
33
3.2.3
Description
of
Rotational
Crop
Metabolism,
including
identification
of
major
metabolites
and
specific
routes
of
biotransformation
..........
34
3.3
Environmental
Degradation
............................................................................
34
3.4
Summary
of
Residues
for
Tolerance
Expression
and
Risk
Assessment
.........
36
4.0
Hazard
Characterization/
Assessment..............................................................................
36
4.1
Hazard
Characterization
.................................................................................
36
4.2.1
Adequacy
of
the
Toxicity
Data
Base....................................................
42
4.2.2
Evidence
of
Neurotoxicity
....................................................................
42
4.2.3
Developmental
Toxicity
Studies...........................................................
42
4.2.4
Reproductive
Toxicity
Study
...............................................................
42
4.2.5
Pre­
and/
or
Postnatal
Toxicity................................................................
43
4.3
Hazard
Identification
and
Toxicity
Endpoint
Selection.................................
44
4.3.1.
Acute
Reference
Dose
(
aRfD)
..............................................................
44
4.3.2.
Chronic
Reference
Dose
(
cRfD)
..........................................................
46
4.3.3.
Incidental
Oral
Exposure
(
Short
and
Intermediate
Term)................
47
4.3.4.
Dermal
Absorption..............................................................................
48
4.3.5.
Dermal
Exposure
(
Acute)....................................................................
48
4.3.6.
Dermal
Exposure
(
Short­
and
Intermediate­
Term)
..........................
48
4.3.7.
Inhalation
Exposure
(
Acute)
...............................................................
49
4.3.8.
Inhalation
Exposure
(
Short
and
Intermediate
Term)
........................
49
4.3.9.
Inhalation
Exposure
(
Long
Term)
......................................................
49
4.3.10.
Margins
of
Exposure
.........................................................................
50
4.3.11.
Recommendation
for
Aggregate
Exposure
Risk
Assessments..........
51
4.3.12.
Classification
of
Carcinogenic
Potential
...........................................
51
4.4
FQPA
Safety
factor..........................................................................................
53
4.5.
Endocrine
Disruption
......................................................................................
54
5.0
Public
Health
Data
...........................................................................................................
55
5.1
Incident
Reports...............................................................................................
55
Page
4
of
151
5.2
Other
................................................................................................................
55
6.0
Exposure
Characterization/
Assessment...........................................................................
57
6.1
Dietary
Exposure/
Risk
Pathway......................................................................
57
6.1.1
Residue
Profile......................................................................................
57
6.1.2
Acute
and
Chronic
Dietary
Exposure
and
Risk..................................
61
6.2
Water
Exposure/
Risk
Pathway........................................................................
67
6.3
Residential
(
Non­
Occupational)
Exposure/
Risk
Pathway..............................
74
6.3.1
Home
Uses
............................................................................................
74
6.3.2
Recreational
Uses
.................................................................................
79
6.3.3
Other
(
Spray
Drift,
etc.).......................................................................
79
7.0
Aggregate
Risk
Assessments
and
Risk
Characterization................................................
84
7.1
Acute
Aggregate
Risk
......................................................................................
85
7.2
Short­
Term
Aggregate
Risk.............................................................................
86
7.3
Intermediate­
Term
Aggregate
Risk
................................................................
88
7.4
Long­
Term
Aggregate
Risk
.............................................................................
88
7.5
Aggregate
Cancer
Risk
....................................................................................
89
8.0
Cumulative
Risk
Characterization/
Assessment
..............................................................
89
9.0
Occupational
Exposure/
Risk
Pathway
............................................................................
90
10.0
Data
Needs
and
Label
Requirements
..........................................................................
104
10.1
Toxicology
......................................................................................................
104
10.3
Residue
Chemistry.........................................................................................
104
10.4
Occupational
and
Residential
Exposure
.......................................................
104
REFERENCES......................................................................................................................
106
Appendices
............................................................................................................................
115
1.0
Toxicology
Data
Requirements
2.0
Toxicology
Studies
3.0
Residue
Chemistry
Data
Requirements
4.0
Tolerance
Reassessment
Page
5
of
151
1.0
Executive
Summary
The
Health
Effects
Division
(
HED)
has
conducted
a
human
health
risk
assessment
for
the
active
ingredient
dichlorvos
(
2,2­
dichlorovinyl
dimethyl
phosphate),
also
known
as
DDVP,
for
the
purposes
of
making
a
reregistration
eligibility
decision.
Cumulative
risk
assessment
considering
risks
from
other
pesticides
or
chemical
compounds
having
a
common
mechanism
of
toxicity
is
not
addressed
in
this
document.
This
risk
assessment
updates
the
Phase
3
Preliminary
Human
Health
Risk
Assessment,
dated
August
9.
2000,
addresses
the
Public
Comments
submitted
in
accordance
with
Phase
3
of
the
Tolerance
Reassessment
Advisory
Committee
(
TRAC)
Organophosphate
(
OP)
Pilot
Process,
and
additional
error
correction
comments
on
a
June
14,
2005
assessment,
and
uses
endpoints
based
on
human
studies
for
some
scenarios.
The
intentional
dosing,
human
toxicity
study
used
in
this
risk
assessment
has
been
reviewed
by
EPA's
Human
Studies
Review
Board
(
HSRB),
on
April
5,
2006,
as
required
by
EPA's
Human
Subjects
Protections
rule,
40
CFR
part
26
(
effective
April
7,
2006).
Exposures
and
risks
for
all
exposure
scenarios
have
been
recalculated.
Exposure
to
dichlorvos
from
the
use
of
naled
and
trichlorfon
(
which
metabolize
to
dichlorvos)
is
included
in
this
document.

1.1
Use
and
Major
Formulations
Dichlorvos
is
an
organophosphate
insecticide
and
fumigant
registered
for
use
in
controlling
flies,
mosquitos,
gnats,
cockroaches,
fleas,
and
other
insect
pests.
Formulations
of
dichlorvos
include
pressurized
liquids,
granulars,
emulsifiable
concentrates,
total
release
aerosols,
and
impregnated
materials.
Dichlorvos
is
applied
with
aerosols
and
fogging
equipment,
with
spray
equipment,
and
through
slow
release
from
impregnated
materials,
such
as
resin
strips
and
pet
collars.

Dichlorvos
is
registered
to
control
insect
pests
on
agricultural
sites;
commercial,
institutional
and
industrial
sites;
and
for
domestic
use
in
and
around
homes
(
i.
e.,
resin
strips)
and
on
pets.
Dichlorvos
is
used
preplant
in
mushroom
houses,
and
postharvest
in
storage
areas
for
bulk,
packaged
and
bagged
raw
and
processed
agricultural
commodities,
food
manufacturing/
processing
plants,
animal
premises,
and
non­
food
areas
of
food­
handling
establishments.
It
is
also
registered
for
direct
dermal
treatment
of
cattle
and
poultry,
and
swine,
sheep,
and
goats.

The
mechanism
of
pesticidal
action
of
dichlorvos
is
inhibition
of
cholinesterase.
The
Agency
has
determined
that
the
adverse
effects
caused
by
dichlorvos
that
are
of
primary
concern
to
human
health
are
neurological
effects
related
to
inhibition
of
cholinesterase
activity.

1.2
Regulatory
History
The
Agency
initiated
a
Special
Review
for
pesticide
products
containing
dichlorvos
on
February
24,
1988,
by
publishing
Position
Document
1
(
PD
1).
At
that
time,
the
Agency
was
concerned
that
exposure
to
dichlorvos
from
registered
uses
posed
an
unreasonable
carcinogenic
risk
and
that
there
were
inadequate
margins
of
exposure
for
cholinesterase
inhibition
and
liver
effects
to
exposed
individuals.
After
evaluation
of
information
submitted
through
the
Special
Review
Process,
the
Agency
conducted
another
risk
assessment
for
dichlorvos.
In
1995,
the
Page
6
of
151
Agency
concluded
that
dichlorvos
posed
carcinogenic
risks
of
concern
to
the
general
population
from
dietary
exposure.
The
Agency
also
concluded
in
1995
that
dichlorvos
posed
risks
of
concern
for
cholinesterase
inhibition
to
residents
and
to
individuals
mixing,
loading,
and
applying
this
pesticide,
as
well
as
to
those
reentering
treated
areas.
Subsequently,
the
Agency
issued
a
Preliminary
Determination
to
Cancel
Certain
Registrations
and
Draft
Notice
of
Intent
to
Cancel
the
dichlorvos
uses
which
posed
the
greatest
risks,
also
called
Position
Document
2/
3
or
PD
2/
3
(
60
FR
50338,
September
28,
1995).
In
its
1995
Preliminary
Determination
(
PD
2/
3),
the
Agency
concluded
that
the
risks
outweighed
the
benefits
for
most
uses
of
dichlorvos
and,
therefore,
recommended
a
variety
of
measures
to
reduce
those
risks.
The
Agency
proposed
cancellation
of
certain
uses
of
dichlorvos
and
cancellation
of
other
uses
unless
certain
labeling
modifications
were
made
to
reduce
risk.

The
PD
2/
3
Federal
Register
Notice
provided
for
a
formal
comment
period,
which
closed
on
December
28,
1995.
Comments
were
received,
and
are
contained
in
a
public
docket
identified
as
"
OPP­
30000/
56."
Major
comments
to
the
PD
2/
3
were
submitted
to
the
Agency
by
Amvac
Chemical
Corporation,
the
Japanese
Resin
Strip
Manufacturer's
Association,
grower
groups,
and
the
general
public.
Some
of
the
comments
contained
additional
data
pertaining
to
the
risks
posed
by
dichlorvos.

The
Agency
has
also
identified
newer
exposure
and
toxicity
data
pertaining
to
dichlorvos
that
have
become
available
since
publication
of
the
Notice
of
Preliminary
Determination
to
Cancel
certain
Registrations
and
Draft
Notice
of
Intent
to
Cancel
(
PD
2/
3).
In
addition
to
the
newer
data
and
information
described
above,
the
Food
Quality
Protection
Act
of
1996
has
effectively
modified
the
considerations
the
Agency
uses
to
assess
the
risks
of
pesticides.
Therefore,
the
Agency
has
re­
evaluated
the
toxicology
and
exposure
databases
for
dichlorvos
to
make
a
determination
of
potential
special
susceptibility
of
infants
and
children,
as
mandated
by
FQPA.
In
addition,
the
Agency
has
reviewed
new
information
pertaining
to
dietary
exposure
and
performed
a
refined
dietary
exposure
assessment.
The
Agency
has
also
refined
the
occupational
and
residential
exposure
assessment
for
dichlorvos
with
new
information
and
new
methodologies
that
were
previously
unavailable.

The
following
issues
pertaining
to
the
ongoing
dichlorvos
risk
assessment
were
presented
to
the
FIFRA
Science
Advisory
Panel
(
SAP)
on
July
28,
1998:
(
1)
the
selection
of
an
FQPA
safety
factor
for
dichlorvos
and
(
2)
how
the
Agency
conducted
the
resin
strip
exposure
assessment.

This
risk
assessment
has
been
conducted
for
dichlorvos
in
conjunction
with
the
public
review
and
comment
process
for
all
of
the
organophosphate
pesticides.
The
public
process
for
dichlorvos
was
initiated
on
December
3,
1998,
when
the
Phase
1
risk
assessment
was
provided
to
the
registrant
for
"
error
only"
review.
In
Phase
2
of
the
OP
pilot
process,
the
error
correction
comments
from
the
registrant
were
incorporated.
On
October
11,
2000,
the
Preliminary
Risk
Assessment
for
dichlorvos
was
issued
for
public
comment.
This
revision
incorporates
Agency
response
to
the
public
comments
submitted
in
Phase
3
of
the
OP
pilot
process.
Comments
on
the
dichlorvos
Preliminary
Risk
Assessment
were
received
from
Amvac,
NRDC,
and
dichlorvos
users.
Additional
exposure
analyses
were
conducted
for
different
sizes
of
resin
strips
and
for
pet
Page
7
of
151
collars.
Comments
were
received
from
a
second
registrant
"
error
correction"
comment
period
and
from
the
HSRB
from
an
April
5,
2006
meeting.

1.3
Hazard
Identification
and
Dose­
Response
Assessment
The
toxicology
database
for
dichlorvos
is
complete
with
respect
to
the
OPPTS
Guideline
requirements.
For
acute
toxicity,
technical
dichlorvos
was
placed
in
Toxicity
Categories
II,
I
and
II,
respectively,
for
the
oral,
dermal
and
inhalation
routes
and
in
Toxicity
Category
III
and
IV
for
eye
and
dermal
irritation,
respectively.
Dichlorvos
did
not
cause
organophosphate
induced
delayed
neurotoxicity
(
OPIDN)
in
the
hen
following
single
or
multiple
(
28
days)
exposures.
Following
a
single
oral
dose
to
rats,
dichlorvos
was
associated
with
a
variety
of
neurological
and
physiological
changes.
Subchronic
and
chronic
oral
exposures
in
rats
and
dogs
as
well
as
chronic
inhalation
exposure
in
rats
resulted
in
significant
decreases
in
plasma,
red
blood
cell
and/
or
brain
cholinesterase
activity.
The
carcinogenic
potential
of
dichlorvos
has
been
classified
as
"
suggestive"
under
the
1999
Draft
Agency
Cancer
Guidelines
and
no
quantitative
assessment
of
cancer
risk
is
required.
There
was
no
evidence
of
increased
susceptibility
following
in
utero
exposures
to
rats
and
rabbits
as
well
as
pre/
post
natal
exposure
to
rats.
Also,
there
was
no
evidence
of
abnormalities
in
the
development
of
the
fetal
nervous
system
in
the
frbrlopmrnysl/
neurotoxicity
studies
submitted
to
the
Agency.

The
toxicity
endpoints
used
in
this
document
to
assess
risks
include
acute
and
chronic
dietary
reference
doses
(
RfDs),
and
short­,
intermediate­
and
long­
term
dermal
LOAELs
and
inhalation
no
observed
adverse
affect
levels
(
NOAELs).
Endpoints
based
on
human
studies
have
been
used
to
assess
some
scenarios.

Inhibition
of
cholinesterase
activity
was
the
toxicity
endpoint
selected
for
acute
and
chronic
dietary,
as
well
as,
short
term,
intermediate
term,
and
long
term
(
chronic)
occupational
and
residential
risk
assessments.
The
Uncertainty
Factor(
s)
ranged
from
30
to
100
depending
on
the
route
and
duration
of
exposures.

The
HED
dichlorvos
team
evaluated
the
hazard
and
exposure
data
to
determine
if
the
FQPA10x
safety
factor
should
be
retained,
reduced
or
removed
focusing
primarily
on
the
following
points:
1)
the
standard
developmental
and
reproductive
toxicity
studies
and
the
developmental
neurotoxicity
study
submitted
to
the
Agency
showed
no
residual
concern
for
increased
susceptibility
of
rats,
or
rabbits
to
in
utero
and/
or
postnatal
exposure
to
dichlorvos;
2)
in
single
dose
(
acute)
studies
with
dichlorvos
in
rats,
there
were
no
differences
with
respect
to
either
RBC
or
brain
cholinesterase
inhibition
between
preweaning
and
adult
rats;
3)
in
repeated
dose
studies
with
dichlorvos
in
rats,
young
rats
were
no
more
sensitive
than
adult
rats
with
respect
to
inhibition
of
RBC
and
brain
cholinesterase;
and
4)
sufficient
data
were
available
to
ensure
that
the
dietary
(
food
and
drinking
water)
and
non­
dietary
(
residential)
risk
assessments
do
not
underestimate
potential
exposures
and
risks
for
infants
and
children
from
the
use
of
dichlorvos.
Some
scenarios
used
endpoints
ased
on
a
LOAEL,
and
the
3x
uncertainty
factor
used
is
considered
part
of
the
FQPA
safety
factor.

The
dichlorvos
team
determined
that
there
no
residual
concerns
for
increased
susceptibility
of
infants
and
children.
An
FQPA
safety
factor
of
1x
is
considered
appropriate.
Page
8
of
151
1.4
Exposure/
Risk
Assessment
and
Risk
Characterization
Dietary
exposure
to
dichlorvos
residues
may
occur
as
a
result
of
use
of
dichlorvos
on
or
at
a
variety
of
sites,
including
mushroom
houses,
bulk­
stored
and
packaged
or
bagged
nonperishable
processed
and
raw
food,
commercial
food
processing
plants,
direct
dermal
pour­
on
treatment
to
livestock,
and
livestock
premises
treatment.
Two
other
pesticides,
naled
and
trichlorfon,
degrade
to
dichlorvos
through
plant
and
animal
metabolism
and
other
processes.
Residues
of
dichlorvos
from
the
use
of
naled
on
crops
are
included
in
the
dichlorvos
dietary
exposure
assessment.
All
trichlorfon
field
crop
food
uses
have
been
canceled
and
associated
tolerances
revoked;
therefore,
the
Agency
does
not
expect
measurable
dichlorvos
residues
from
use
of
trichlorfon
on
field
crops.
The
trichlorfon
tolerances
on
livestock
commodities
remain;
dermal
use
on
beef
cattle
is
supported
as
an
import
use.
Non­
detectable
dichlorvos
residues
in
livestock
commodities
are
expected
as
a
result
of
trichlorfon
use,
and
dichlorvos
was
not
a
significant
metabolite
in
the
trichlorfon
dermal
metabolism
study.
Therefore,
dietary
(
food)
exposure
to
dichlorvos
residues
resulting
from
use
of
trichlorfon
is
considered
negligible
for
the
purposes
of
this
risk
assessment.

Most
product
and
residue
chemistry
data
requirements
for
dichlorvos
have
been
fulfilled.
However,
the
reregistration
data
requirements
for
storage
stability
(
Guideline
860.1380),
for
meat,
milk,
poultry,
and
egg
studies
(
Guideline
860.1480),
and
directions
for
use
(
Guideline
860.1200)
have
not
been
fulfilled.

Dietary
(
food
only)
exposure
estimates
for
dichlorvos
have
been
refined
with
residue
data
from
USDA's
Pesticide
Data
Program
(
PDP),
FDA
surveillance
monitoring
data
and
FDA
Total
Diet
Study
(
TDS)
data.
Anticipated
residues
for
dichlorvos
have
been
revised
to
incorporate
these
residue
data.
The
acute
and
chronic
dietary
exposure
analyses
for
dichlorvos
(
including
contribution
from
naled
and
negligible
contribution
from
trichlorfon)
were
conducted
using
the
Dietary
Exposure
Evaluation
Model
(
DEEM
 
)
software.
Acute
dietary
exposure
did
not
exceed
the
Agency's
level
of
concern
for
the
99.9th
percentile
of
the
population.
Chronic
dietary
exposure
did
not
exceed
2%
of
the
cPAD
for
all
subpopulations,
which
is
below
the
Agency's
level
of
concern
of
100%.

The
Environmental
Fate
and
Effects
Division
(
EFED)
evaluated
the
potential
for
dichlorvos
to
contaminate
water
from
the
use
of
dichlorvos,
naled
or
trichlorfon.
EFED
has
limited
ground
water
monitoring
data
for
dichlorvos,
naled,
and
trichlorfon
from
the
states
of
California
and
Hawaii
in
the
"
Pesticides
in
Groundwater"
database.
These
data
indicate
that
naled,
dichlorvos,
or
trichlorfon
have
not
been
detected
in
groundwater;
however,
these
data
were
not
targeted
to
the
pesticide
use
area.
Therefore,
the
SCIGROW
model
was
used
to
estimate
concentrations
of
dichlorvos,
naled,
and
trichlorfon
in
groundwater.
OPP
does
not
have
any
surface
monitoring
data
on
the
concentrations
of
dichlorvos,
naled,
or
trichlorfon
at
the
present
time.
Therefore,
the
Tier
II
screening
models
PRZM
and
EXAMS
with
the
Index
Reservoir
and
Percent
Crop
Area
adjustment
(
IR­
PCA
PRZM/
EXAMS)
were
used
to
estimate
surface
water
concentrations
for
dichlorvos
resulting
from
the
use
of
naled,
trichlorfon
and
dichlorvos.

Although
PDP
water
monitoring
data
were
available,
and
all
samples
had
non­
detectable
residues
(
LODs
ranged
from
6
to
22.5
ppt),
these
data
were
not
considered
sufficiently
Page
9
of
151
representative.
In
the
absence
of
sufficient
water
monitoring
data,
estimated
drinking
water
concentrations
(
EDWCs)
of
dichlorvos
from
the
use
of
dichlorvos,
naled,
and
trichlorfon
in
water
were
compared
with
Drinking
Water
Levels
of
Comparison
(
DWLOCs)
for
acute
or
chronic
systemic
toxicity.
EDWCs
of
dichlorvos
in
ground
and
surface
water
were
derived
from
conservative
screening
level
models.
A
DWLOC
is
a
theoretical
upper
limit
on
a
pesticide's
concentration
in
drinking
water
in
light
of
total
aggregate
exposure
to
a
pesticide
in
food,
drinking
water,
and
through
residential
uses.
HED
uses
DWLOCs
internally
in
the
risk
assessment
process
as
a
surrogate
measure
of
potential
exposure
associated
with
pesticide
exposure
through
drinking
water.

Residential
and
occupational
exposure
scenarios
can
be
described
as
acute,
short
term
(
1­
30
days),
intermediate
term
(
1
month
to
6
months),
and
long
term
or
chronic
(
6
months
to
a
lifetime).
The
dichlorvos
residential
exposure
scenarios
for
aerosol
spray
cans
(
both
homeowner
application
and
post­
application)
are
considered
acute
exposure
scenarios.
Lawn
post­
application
from
treatment
with
trichlorfon
is
considered
a
short­
term
exposure
scenario.
Resin
pest
strips
and
pet
flea
collars
are
long
term
exposure
scenarios.
Occupational
exposure
scenarios
are
typically
acute
or
short­
term,
except
for
a
few
intermediate
term
occupational
exposure
scenarios,
applications
in
mushroom
houses
and
direct
application
to
livestock.

Exposure
assessments
for
a
number
of
occupational
and
residential
scenarios
were
derived
from
limited
data
from
the
scientific
literature,
textbooks,
knowledge
of
cultural
practices,
and
the
Residential
SOPs
(
U.
S.
EPA,
1997a).
Other
estimates,
particularly
in
the
residential
environment,
were
derived
from
surrogate
data
from
the
Pesticide
Handlers
Exposure
Database
(
PHED,
version
1.1),
chemical
specific
data
included
in
the
Outdoor
Residential
Exposure
Task
Force
(
ORETF)
database,
Residential
Exposure
Joint
Venture
(
REJV)
data,
and
additional
chemical
specific
monitoring
data,
including
biomonitoring
of
a
urinary
metabolite,
in
combination
with
models
and
literature
studies.

Residential
exposure
scenarios
do
not
exceed
the
Agency's
level
of
concern.
Residential
exposure
from
the
use
of
the
pressurized
aerosol
has
been
recalculated
due
to
new
data
from
the
Residential
Exposure
Joint
Venture
(
REJV).

Residential
and
occupational
exposures
to
dichlorvos
may
also
result
from
uses
of
naled
and
trichlorfon.
The
only
naled
residential
use
is
a
mosquitocide
public
health
use.
For
this
use,
the
application
rate
of
naled
is
very
low,
and
we
expect
that
any
dichlorvos
formed
dissipates
rapidly.
Further
discussion
is
found
in
the
exposure
assessment
section
of
this
document.
Approximately
25%
of
trichlorfon
is
expected
to
degrade
to
dichlorvos
at
the
pH
of
a
typical
lawn.

None
of
the
aggregate
risks
exceed
our
level
of
concern,
considering
food,
water,
and
residential
exposures,
for
all
residential
exposure
scenarios.
Food
and
water
exposure
were
very
small
compared
to
the
residential
exposure
estimates.

Occupational
handler
scenarios
do
not
exceed
the
Agency's
level
of
concern,
after
voluntary
cancellations,
addition
of
additional
PPE,
and
longer
reentry
intervals
(
REIs).
Page
10
of
151
1.5
Human
Studies
This
risk
assessment
relies
in
part
on
data
from
studies
in
which
adult
human
subjects
were
intentionally
exposed
to
a
pesticide
or
other
chemical.
These
studies,
listed
below,
have
been
determined
to
require
a
review
of
their
ethical
conduct,
and
EPA
is
currently
preparing
these
ethics
reviews
in
accordance
with
EPA
Human
Subjects
Protections
rule,
40
CFR
part
26.

Gledhill,
A.,
1997.
Dichlorvos:
A
Single
Blind,
Placebo
Controlled,
Randomised
Study
to
Investigate
the
Effects
of
Multiple
Oral
Dosing
on
Erythrocyte
Cholinesterase
Inhibition
in
Healthy
Male
Volunteers:
Lab
Project
Number:
CTL/
P/
5392:
XH6063.
Unpublished
study
prepared
by
Zeneca
Central
Toxicology
Lab.
52
p.
MRID
44248801.

Emlay,
D.;
Rudolph,
R.
(
1977)
Determination
of
the
Quantity
of
Carbaryl
Removed
by
Petting
Dogs
Wearing
16%
Carbaryl
Dog
Collars:
Lab
Project
Number:
TR­
506.
Unpublished
study
prepared
by
Zoecon
Industries,
Inc.
14
p.
{
OPPTS
875.1500}
MRID
45792201.

Klonne,
D.
(
1999)
Integrated
Report
for
Evaluation
of
Potential
Exposures
to
Homeowners
and
Professional
Lawn
Care
Operators
Mixing,
Loading,
and
Applying
Granular
and
Liquid
Pesticides
to
Residential
Lawns:
Lab
Project
Number:
OMAOO5:
OMAOO1:
OMAOO2.
Unpublished
study
prepared
by
Ricerca,
Inc.,
and
Morse
Laboratories.
2213
p.
(
MRID
44972201)
(
ORETF
study)

McDonald,
E.,
1991.
Indoor
Fogger
Dermal
and
Inhalation
Exposure
Study
with
DDVP:
Lab
Project
Number:
4­
02­
333.
Unpublished
study
prepared
by
British
Columbia
Research
Corp.
331
p.
MRID
41928801.

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

In
addition,
the
Human
Subjects
Protections
rule
requires
that
the
Gledhill
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
Gledhill
study
to
the
HSRB
at
a
meeting
on
April
2
 
4,
2006.
The
HSRB
discussed
the
Gledhill
study
extensively
during
this
meeting
and
has
prepared
a
draft
written
report
summarizing
its
discussions.
The
Agency
believes
that
the
oral
comments
of
the
HSRB
and
the
draft
report
provided
a
sufficient
indication
of
the
conclusions
likely
to
appear
in
the
HSRB's
final
report
that
EPA
could
confidently
move
ahead.
Accordingly,
the
Agency
has
decided
to
issue
this
risk
assessment
prior
to
receiving
the
final
written
report
of
the
HSRB.
The
Agency
will
carefully
review
the
HSRB's
final
report
on
DDVP
prior
to
issuing
its
final
reregistration
eligibility
decision
to
determine
whether
the
HSRB's
report
contains
conclusions
that
warrant
reconsideration
of
this
risk
assessment
2.0
Ingredient
Profile
Page
11
of
151
Dichlorvos
is
a
chlorinated
organophosphorus
insecticide,
with
technical
and
manufacturing
use
products
registered
to
Amvac
Chemical
Corporation
and
Drexel
Chemical
Company.
Formulations
and
EPA
Reg.
Nos.
are
summarized
below
in
table
2.0.

Table
2.0.
Registered
Manufacturing­
Use
Products
of
Dichlorvos,
as
described
in
OPPIN.

Formulation
EPA
Reg.
No.
Registrant
93%
T
5481­
96
Amvac
Chemical
Corporation
98%
T
1,2
5481­
461
98%
T
1,2
5481­
462
90%
FI
3
19713­
353
Drexel
Chemical
Company
1
Repackaged
from
an
EPA­
registered
product.
We
note
that
there
is
not
another
EPA
registered
product
containing
98%
dichlorvos.
This
discrepancy
must
be
cleared
up.
2
OPPIN
currently
identifies
this
product
as
an
FI;
however,
it
is
correctly
identified
as
a
T.
3
Sequentially
transferred
from
EPA
Reg.
Nos.
8521­
126,
904­
396,
and
44215­
139.
T
=
Technical
Product
FI
=
Formulation
intermediate
2.1
Summary
of
Registered/
Proposed
Uses
The
basic
producer
of
dichlorvos
is
Amvac
Chemical
Corporation.
According
to
an
OPPIN
search,
conducted
on
6/
12/
06,
there
are
98
active
end­
use
products
(
EPs)
registered
under
FIFRA
Section
3
containing
dichlorvos,
29
of
which
are
registered
to
Amvac;
there
is
one
Special
Local
Need
(
SLN)
registration
under
FIFRA
Section
24(
c)
associated
with
these
Amvac
EPs,
and
one
Special
Local
Need
(
SLN)
registration
under
FIFRA
Section
24(
c)
associated
with
another
EP.
The
registered
food
and
feed
use
patterns
of
dichlorvos
EP
labels
subject
to
reregistration
are
presented
in
table
2.1.
Residential
use
patterns
are
discussed
in
Section
6
of
this
document.
Occupational
use
patterns
are
discussed
in
Section
9
of
this
document.
In
addition,
Amvac
submitted
copies
of
two
product
labels
for
the
technical
formulation
(
EPA
Reg.
Nos.
5481­
461
and
5481­
462)
which
include
directions
for
use
for
various
sites.
Page
12
of
151
Table
2.1.
Food/
Feed
Use
Patterns
on
EP
Labels
Subject
to
Reregistration
for
Dichlorvos
(
Case
0310).

Site
Application
Type
Formulation
[
EPA
Reg.

No.]
Application
Rate,
ai
1
Use
Directions
and
Limitations
2
Agricultural
commodities
(
bulk
storage
of
nonperishable
raw
and
processed
agricultural
commodities
including
raw
grains,
corn,
soybeans,
cocoa
beans,
and
peanuts)
20%
Impr
[
5481­
338]
Use
of
product
where
unwrapped
food
is
stored
or
allowing
the
strip
to
come
in
contact
with
food
or
cooking
utensils
is
prohibited.

20%
Impr
[
5481­
344]
Use
in
kitchens,
restaurants,
or
areas
where
food/
feed
are
prepared
or
processed,
use
in
food/
feed
processing
or
food/
feed
manufacturing
areas
of
food/
feed
processing
and
food/
feed
manufacturing
plants
are
prohibited.

Premise
treatment
20%
Impr
[
5481­
348]
10.5
g
of
product/

50­
100
cu.
ft
or
80
g
of
product/

900­
1200
cu.
ft
Use
in
kitchens,
restaurants,
or
areas
where
food
is
prepared
or
served
and
use
in
edible
product
areas
of
food
processing
plants
are
prohibited.

Greenhouses
(
not
containing
food
commodities)

Fog
application
[
hand­
held
fogger
is
no
longer
permitted]
0.37
lb/
gal
EC
[
5481­
220]
0.004
lb/
1,000
cu.
ft
Applications
may
be
made
using
a
cold
aerosol
generator.
Hand
held
foggers
are
no
longer
permitted.

Mushroom
houses
50%
FlC
[
5481­
203]
2%
finished
spray
[
6.25
oz/
10,000
cu.
ft]
Applications
may
be
made
in
1,1,1­
trichloroethane
using
a
cold
aerosol
generator.

Applications
may
be
made
twice
a
week
during
spawn
run;
thereafter
use
as
needed.
A
1­

day
PHI
has
been
established
for
mushrooms.

2%
finished
spray
[
10
oz/
10,000
cu.
ft]

5
g/
10,000
cu.
ft
Applications
may
be
made
in
deodorized
base
kerosene
using
a
cold
aerosol
generator.

Applications
may
be
made
twice
a
week
during
spawn
run;
thereafter
use
as
needed.
A
1­

day
PHI
has
been
established
for
mushrooms.

Fog
application
[
hand­
held
fogger
is
no
longer
permitted]
0.37
lb/
gal
EC
[
5481­
220]
0.004
lb/
1,000
cu.
ft
Applications
may
be
made
using
a
cold
aerosol
generator.
Applications
may
be
made
twice
a
week
during
spawn
run;
thereafter
use
as
needed.

Brush
on
/
coarse
spray
2
lb/
gal
EC
[
72­
365]

(
canceled)
0.00125
lb/
100
sq
ft
Coarse
spray
or
paint
on
walls,
around
doors,
ventilators
&
cracks
before
mushrooms
come
into
production.
Use
as
0.5%
solution
 
1
pint
of
0.5%
solution
per
100
sq
ft.,
up
to
10
days
before
crop
emerges
on
soil
beds.
Do
not
spray
inside
walls
after
mushrooms
appear
on
beds.
After
mushrooms
appear,
spray
only
the
outside
of
the
building.

Tobacco
Warehouse:
Page
13
of
151
Table
2.1.
Food/
Feed
Use
Patterns
on
EP
Labels
Subject
to
Reregistration
for
Dichlorvos
(
Case
0310).

Site
Application
Type
Formulation
[
EPA
Reg.

No.]
Application
Rate,
ai
1
Use
Directions
and
Limitations
2
1.59
lb/
gal
EC
[
5481­
206]

4
lb/
gal
EC
[
5481­
204]

1.15
lb/
gal
SC
[
5481­
207]

8.39
lb/
gal
SC
[
5481­
201]
2%
finished
spray
[
19­
38
fl.
oz/
10,000
cu.
ft]

or
10­
20
g/
10,000
cu.
ft
Fogging
applications
may
be
made
with
odorless
oil
or
other
non­
flammable
oil
solvents
known
to
be
safe
for
use
in
tobacco
warehouses.
Applications
may
be
repeated
as
needed.
Applications
may
be
made
only
in
warehouses
storing
unfinished
tobacco.

Space
treatment
in
closed
warehouses
[
Hand­
Held
Foggers
are
no
longer
permitted]
0.37
lb/
gal
EC
[
5481­
220]
0.37
lb/
336,000
cu.
ft
Fogging
applications
may
be
repeated
as
needed.
Applications
may
be
made
only
in
warehouses
storing
unfinished
tobacco.

Food­
handling
establishments
(
including
households;
restaurants;
theaters;
food
processing
plants;
industrial
plants;
and
warehouses)

Indoor
treatment
Directed
spray
application
Indoor
treatment
Remote
Fog
Application
4
lb/
gal
EC
[
5481­
204]

20%
PrL
[
47000­
71]
0.5%
finished
spray
2.5
g/
1000
cu.
ft.
Applications
may
be
made
with
deodorized
base
oil
or
water
using
a
low
pressure
sprayer
to
treat
localized
areas
where
insects
may
infest
around
baseboards,
cracks,
walls,
doors,

window
frames,
and
localized
areas
of
floors.
Use
in
edible
product
areas
of
food
processing
plants,
restaurants,
or
other
areas
where
food
is
commercially
prepared
or
processed
and
use
in
serving
areas
while
food
is
exposed
is
prohibited
Application
made
by
timer
when
buildings
are
unoccupied.
Building
should
be
closed
and
ventilation
kept
to
a
minimum.
Lock
all
entrances,
and
do
not
allow
unprotected
workers
to
enter
the
building
when
being
treated.

Food­
handling
establishments
(
including
theaters;
food
processing
plants;
industrial
plants;
and
warehouses)
Page
14
of
151
Table
2.1.
Food/
Feed
Use
Patterns
on
EP
Labels
Subject
to
Reregistration
for
Dichlorvos
(
Case
0310).

Site
Application
Type
Formulation
[
EPA
Reg.

No.]
Application
Rate,
ai
1
Use
Directions
and
Limitations
2
Indoor
treatment
Space
spray
application
[
Hand­
Held
Foggers
are
no
longer
permitted]
0.37
lb/
gal
EC
[
5481­
220]

1.59
lb/
gal
EC
[
5481­
206]

4
lb/
gal
EC
[
5481­
204]

1.15
lb/
gal
SC
[
5481­
207]

2
lb/
gal
SC
[
5481­
334]

8.39
lb/
gal
SC
[
5481­
201]
1%
finished
spray
[
1
gal/
64,000
cu.
ft]
Fogging
or
misting
applications
may
be
made
with
deodorized
base
oil
or
water
using
fogging
or
misting
equipment
to
treat
indoor
areas.
Applications
are
to
be
made
when
the
plants
are
not
in
operation.
Food
should
be
removed
and
food­
handling
equipment
covered
prior
to
application
or
washed
with
suitable
cleaner
and
potable
water
after
application.

Food­
handling
establishments
[
including
areas
for
receiving,
storage,
packing
(
canning,
bottling,
wrapping,
boxing),
preparing,
edible
waste
storage,

and
enclosed
processing
systems
(
mills,
dairies,
edible
oils,
syrups),
and
serving
areas]

Indoor
crack
and
crevice
treatment
0.25
lb/
gal
EC
[
5481­
217]

0.5
lb/
gal
EC
[
5481­
216]
0.1%
finished
spray
Applications
may
be
made
in
water
or
oil
and
may
be
applied
by
directing
small
amounts
into
crack
and
crevices,
in
points
between
different
elements
of
construction,
and
between
equipment
legs
and
bases.
Applications
in
food
areas
other
than
crack
and
crevice
treatments
are
prohibited.

Nonfood/
feed
areas
of
food­
handling
establishments
[
including
garbage
rooms,
lavatories,
floor
drains
(
sewers),
entries
and
vestibules,
offices,
locker
rooms,
machine
rooms,
boiler
rooms,
garages,
mop
closets,
and
storage
(
after
canning
or
bottling)]
Page
15
of
151
Table
2.1.
Food/
Feed
Use
Patterns
on
EP
Labels
Subject
to
Reregistration
for
Dichlorvos
(
Case
0310).

Site
Application
Type
Formulation
[
EPA
Reg.

No.]
Application
Rate,
ai
1
Use
Directions
and
Limitations
2
Indoor
treatment
Directed
spray
application
0.37
lb/
gal
EC
[
5481­
220]

1.59
lb/
gal
EC
[
5481­
206]

1.15
lb/
gal
SC
[
5481­
207]

2
lb/
gal
SC
[
5481­
334]

8.39
lb/
gal
SC
[
5481­
201]
0.5%
finished
spray
Applications
may
be
made
with
deodorized
base
oil
or
water
using
a
low
pressure
sprayer
to
treat
localized
areas
where
insects
may
infest
around
baseboards,
cracks,
walls,
doors,

window
frames,
and
localized
areas
of
floors.
Use
in
edible
product
areas
of
food
processing
plants,
restaurants,
or
other
areas
where
food
is
commercially
prepared
or
processed
and
use
in
serving
areas
while
food
is
exposed
are
prohibited.

4.48
lb/
gal
SC
[
5481­
202]
0.5%
finished
spray
Applications
may
be
made
with
deodorized
base
oil
using
a
low
pressure
sprayer
to
treat
localized
areas
where
insects
may
infest
around
baseboards,
cracks,
walls,
doors,
window
frames,
and
localized
areas
of
floors.
Use
in
food/
feed
handling
areas
of
food/
feed
handling
establishments,
restaurants
or
other
areas
where
food
is
commercially
prepared
or
served
and
use
to
treat
non­
perishable
bagged
or
bulk
raw
or
processed
commodities
is
prohibited.

10
lb/
gal
SC
[
5481­
200]
0.5%
finished
spray
For
use
in
warehouses,
silos,
bulk
bins,
and
food/
feed
processing,
food/
feed
manufacturing,
handling
and
storage
plants
containing
non­
perishable,
packaged
or
bagged
raw
or
processed
food/
feed
commodities
or
bulk
raw
or
processed
food
commodities.
Applications
may
be
made
with
deodorized
base
oil
using
a
low
pressure
sprayer
to
treat
localized
areas
where
insects
may
infest
around
baseboards,
cracks,
walls,

doors,
window
frames,
and
localized
areas
of
floors.
Use
of
this
product
in
food
processing
plants,
food­
handling
areas
of
restaurants,
or
areas
where
food
is
prepared
or
served,
and
use
to
treat
non­
perishable
bagged
and
or
bulk
stored
raw
or
processed
agricultural
commodities
are
prohibited.
Contamination
of
food,
water,
food
containers,
or
cooking
utensils
is
prohibited.

Nonfood/
feed
areas
of
food­
handling
establishments
[
including
garbage
rooms,
lavatories,
floor
drains
(
sewers),
entries
and
vestibules,
offices,
locker
rooms,
machine
rooms,
boiler
rooms,
garages,
mop
closets,
and
storage
(
after
canning
or
bottling)]
Page
16
of
151
Table
2.1.
Food/
Feed
Use
Patterns
on
EP
Labels
Subject
to
Reregistration
for
Dichlorvos
(
Case
0310).

Site
Application
Type
Formulation
[
EPA
Reg.

No.]
Application
Rate,
ai
1
Use
Directions
and
Limitations
2
Indoor
spot
treatment
0.25
lb/
gal
EC
[
5481­
217]

0.5
lb/
gal
EC
[
5481­
216]
0.1%
finished
spray
Applications
may
be
made
in
water
or
oil
and
may
be
applied
as
a
coarse
spray
or
with
a
paint
brush
to
areas
where
pests
hide
(
baseboard
areas,
around
water
pipes,
surfaces
behind
and
beneath
sinks,
lockers,
tables,
pallets,
and
similar
areas).
Applications
may
be
repeated
as
needed.
Use
of
this
product
in
edible
product
areas
of
food
processing
plants,

restaurants,
or
other
areas
where
food
is
commercially
prepared
or
processed
and
use
in
serving
areas
where
food
is
exposed
are
prohibited.

1.16
lb/
gal
EC
[
5481­
208]
0.5%
finished
spray
Applications
may
be
made
in
water
and
may
be
applied
to
areas
where
pests
hide
(
around
baseboards,
cracks,
walls,
door
and
window
frames
and
localized
areas
of
floors).
Use
of
this
product
in
food
processing
plants,
food­
handling
areas
of
restaurants,
or
areas
where
food
is
prepared
or
served,
and
use
to
treat
non­
perishable
bagged
and
or
bulk
stored
raw
or
processed
agricultural
commodities
are
prohibited.
Contamination
of
food,
water,
food
containers,
or
cooking
utensils
is
prohibited.

0.5%
RTU
[
5481­
240]
0.5%
spray
Applications
may
be
made
with
a
pump
sprayer
to
areas
where
pests
hide
(
dark
corners
of
room
and
closets,
cracks
and
crevices
in
walls,
behind
and
beneath
sinks,
stoves,

refrigerators,
cabinets,
washing
machines,
cupboards,
bookcases,
and
around
baseboards).
Use
of
this
product
in
food
areas
of
food­
handling
establishments,

restaurants,
or
other
areas
where
food
is
commercially
prepared
or
processed
and
use
in
serving
areas
where
food
is
exposed
or
while
facility
is
operating
are
prohibited.

Indoor
treatment
Space
spray
application
[
Hand­
Held
Foggers
are
no
longer
permitted]
4.48
lb/
gal
SC
[
5481­
202]
1%
finished
spray
[
1
gal/
64,000
cu.
ft]
Fogging
or
misting
applications
may
be
made
with
deodorized
base
oil
using
fogging
or
misting
equipment
to
treat
indoor
areas.
Use
in
bottling
plants,
food
contact
areas
or
meat
slaughter,
and/
or
packing
plants
or
in
frozen
food
plants
is
prohibited.

Nonfood/
feed
areas
of
food­
handling
establishments
[
including
garbage
rooms,
lavatories,
floor
drains
(
sewers),
entries
and
vestibules,
offices,
locker
rooms,
machine
rooms,
boiler
rooms,
garages,
mop
closets,
and
storage
(
after
canning
or
bottling)]
(
continued)

Indoor
treatment
Space
spray
application
[
Hand­
Held
Foggers
are
no
longer
permitted]
10
lb/
gal
SC
[
5481­
200]
1%
finished
spray
[
1
gal/
64,000
cu.
ft]
For
use
in
warehouses,
silos,
bulk
bins,
and
food/
feed
processing,
food/
feed
manufacturing,
handling
and
storage
plants
containing
non­
perishable,
packaged
or
bagged
raw
or
processed
food/
feed
commodities
or
bulk
raw
or
processed
food
commodities.
Fogging
or
misting
applications
may
be
made
with
deodorized
base
oil
using
fogging
or
misting
equipment
to
treat
indoor
areas.
Use
in
bottling
plants,
food
contact
areas
or
meat
slaughter,
and/
or
packing
plants
or
in
frozen
food
plants
is
prohibited.
When
using
in
food
processing,
handling,
and
storage
areas:
(
I)
applications
may
be
made
only
during
times
when
plant
is
not
in
operation
and
no
food
products
are
exposed;
if
bulk,

unpackaged
food
is
exposed,
it
must
be
removed
or
covered
prior
to
treatment;
(
ii)
all
food
processing
surfaces
should
be
covered
during
treatment
or
thoroughly
cleaned
before
using.
Page
17
of
151
Table
2.1.
Food/
Feed
Use
Patterns
on
EP
Labels
Subject
to
Reregistration
for
Dichlorvos
(
Case
0310).

Site
Application
Type
Formulation
[
EPA
Reg.

No.]
Application
Rate,
ai
1
Use
Directions
and
Limitations
2
Indoor
premise
treatment
0.5%
PrL
[
5481­
340]
0.5%
spray
Use
as
a
space
spray
is
prohibited.
Applications
may
be
applied
to
areas
where
pests
hide
(
cracks,
around
baseboards,
cabinets,
walls,
and
woodwork)
and
repeated
as
necessary.

Use
of
this
product
in
edible
product
areas
of
food
processing
plants,
restaurants,
or
other
areas
where
food
is
commercially
prepared
or
processed
and
use
to
treat
non­
perishable
bagged
and
or
bulk
stored
raw
or
processed
agricultural
commodities
are
prohibited.

Contamination
of
utensils,
food,
water,
and
foodstuffs
prohibited.

20%
Impr
[
5481­
344]
10.5
g
of
product/

50­
100
cu.
ft
Use
in
kitchens,
restaurants,
or
areas
where
food/
feed
are
prepared
or
processed,
use
in
food/
feed
processing
or
food/
feed
manufacturing
areas
of
food/
feed
processing
and
food/
feed
manufacturing
plants
are
prohibited.

Animal
Uses
(
Premises)

Farm
buildings
(
including
animal
shelters,
barns,
around
feed
lots,
dairy
barns,
milk
sheds,
loafing
pens,
pig
pens,
poultry
houses,
hog
barns,
stables,

and
other
farm
buildings)

Premise
treatment
Directed
spray
application
1
lb/
gal
EC
[
5481­
41]
0.5%
finished
spray
[
1
qt/
1,000
sq.
ft]
Applications
may
be
made
as
a
coarse,
wet
spray
to
all
exterior
and
interior
surfaces,

treating
window
sills,
around
doors,
fences,
and
ledges
or
as
a
directed
spray
to
floors,

baseboards,
crack
and
crevices
in
wall,
and
along
base
of
walls.
Applications
may
be
made
using
water­
or
oil­
based
sprays;
applications
may
be
repeated
as
necessary.
A
1­
day
preslaughter
interval
(
PSI)
has
been
established.

2
lb/
gal
EC
[
5481­
73]
0.5%
finished
spray
[
1
qt/
1,000
sq.
ft]
Applications
may
be
made
as
a
coarse,
wet
spray
to
surfaces,
treating
window
sills,

doorways,
feed
storage
rooms,
and
alleyways.
Applications
may
be
made
using
water;

applications
may
be
repeated
as
necessary.
Animals
must
be
removed
prior
treatment.

Application
in
areas
where
animals
have
received
a
direct
application
of
DDVP
within
the
past
8
hours
is
prohibited.

0.37
lb/
gal
EC
[
5481­
220]

2
lb/
gal
EC
[
5481­
205]

4
lb/
gal
EC
[
5481­
204]
0.5%
finished
spray
[
1
qt/
1,000
sq.
ft]
Applications
may
be
made
as
a
coarse,
wet
spray
to
surfaces,
treating
window
sills,

doorways,
feed
storage
rooms,
and
alleyways.
Applications
may
be
made
using
water;

applications
may
be
repeated
as
necessary.
Animals
may
be
present
during
treatment.

Contamination
of
water,
feed
or
foodstuffs,
milk
or
milking
utensils
is
prohibited.

Farm
buildings
(
including
animal
shelters,
barns,
around
feed
lots,
dairy
barns,
milk
sheds,
poultry
houses,
hog
barns,
stables,
and
other
farm
buildings)
(
continued)
Page
18
of
151
Table
2.1.
Food/
Feed
Use
Patterns
on
EP
Labels
Subject
to
Reregistration
for
Dichlorvos
(
Case
0310).

Site
Application
Type
Formulation
[
EPA
Reg.

No.]
Application
Rate,
ai
1
Use
Directions
and
Limitations
2
Premise
treatment
Directed
spray
application
1.16
lb/
gal
EC
[
5481­
208]

1.59
lb/
gal
EC
[
5481­
206]

1.15
lb/
gal
SC
[
5481­
207]

4.48
lb/
gal
SC
[
5481­
202]

8.39
lb/
gal
SC
[
5481­
201]

10
lb/
gal
SC
[
5481­
200]
0.5%
finished
spray
[
1
qt/
1,000
sq.
ft]
Applications
may
be
made
as
a
coarse,
wet
spray
to
surfaces,
treating
window
sills,

doorways,
feed
storage
rooms,
and
alleyways.
Applications
may
be
made
using
diesel
oil
or
water;
applications
may
be
repeated
as
necessary.
Direct
treatment
of
animals
or
humans
and
contamination
of
water,
feed
or
foodstuffs,
milk
or
milking
utensils
are
prohibited.

Premise
treatment
Space
spray
application
[
Hand­
Held
Foggers
are
no
longer
permitted]
2
lb/
gal
EC
[
5481­
73]
1%
finished
spray
[
0.5
qt/
8,000
cu.
ft]

or
0.5%
finished
spray
[
1
qt/
8,000
cu.
ft]
Fog
applications
may
be
made
using
diesel
oil.
Animals
must
be
removed
prior
to
treatment.
Prior
to
application,
reduce
air
movement
as
much
as
possible
by
closing
doors,

windows,
and
other
openings.
Application
in
areas
where
animals
have
received
a
direct
application
of
DDVP
within
the
past
8
hours
is
prohibited.

Farm
buildings
(
including
animal
shelters,
barns,
around
feed
lots,
dairy
barns,
milk
sheds,
poultry
houses,
hog
barns,
stables,
and
other
farm
buildings)
(
continued)
Page
19
of
151
Table
2.1.
Food/
Feed
Use
Patterns
on
EP
Labels
Subject
to
Reregistration
for
Dichlorvos
(
Case
0310).

Site
Application
Type
Formulation
[
EPA
Reg.

No.]
Application
Rate,
ai
1
Use
Directions
and
Limitations
2
Premise
treatment
Space
spray
application
[
Hand­
Held
Foggers
are
no
longer
permitted]
0.37
lb/
gal
EC
[
5481­
220]

1.16
lb/
gal
EC
[
5481­
208]

1.59
lb/
gal
EC
[
5481­
206]

2
lb/
gal
EC
[
5481­
205]

4
lb/
gal
EC
[
5481­
204]

1.15
lb/
gal
SC
[
5481­
207]

4.48
lb/
gal
SC
[
5481­
202]

8.39
lb/
gal
SC
[
5481­
201]

10
lb/
gal
SC
[
5481­
200]
1%
finished
spray
[
0.5
qt/
8,000
cu.
ft]

or
0.5%
finished
spray
[
1
qt/
8,000
cu.
ft]
Fog
applications
may
be
made
using
diesel
oil.
Animals
must
be
removed
prior
to
treatment.
Prior
to
application,
reduce
air
movement
as
much
as
possible
by
closing
doors,

windows,
and
other
openings.
Application
in
areas
where
animals
have
received
a
direct
application
of
DDVP
within
the
past
8
hours
is
prohibited.
Contamination
of
water,
feed
or
foodstuffs,
milk
or
milking
utensils
is
prohibited.

Premise
treatment
1%
G
[
5481­
9]
0.04
oz/
1,000
sq.
ft
Bait
applications
may
be
made
to
clean
floor
areas,
ground
areas
outside
enclosures,

window
sills,
or
other
areas
where
flies
congregate.
Applications
are
to
be
made
in
such
a
manner
that
stock
cannot
come
into
contact
with
bait.

Farm
buildings
(
including
animal
shelters,
barns,
around
feed
lots,
dairy
barns,
milk
sheds,
poultry
houses,
hog
barns,
stables,
and
other
farm
buildings)
(
continued)
Page
20
of
151
Table
2.1.
Food/
Feed
Use
Patterns
on
EP
Labels
Subject
to
Reregistration
for
Dichlorvos
(
Case
0310).

Site
Application
Type
Formulation
[
EPA
Reg.

No.]
Application
Rate,
ai
1
Use
Directions
and
Limitations
2
Premise
treatment
Space
spray
application
[
Hand­
Held
Foggers
are
no
longer
permitted]
1
lb/
gal
EC
[
5481­
41]
1%
finished
spray
[
0.5
qt/
8,000
cu.
ft]
Fog
applications
may
be
made
with
animals
present,
provided
a
direct
animal
treatment
of
DDVP
has
not
been
made
in
the
past
8
hours.
Applications
may
be
made
using
water
or
deodorized
kerosene.
Prior
to
application,
reduce
air
movement
as
much
as
possible
by
closing
doors,
windows,
and
other
openings.

Animal
buildings
(
including
horse
barns,
calf
parlors,
hog
parlors,
stables,
poultry
houses,
tack
rooms,
and
dog
kennels)

Premise
treatment
20%
Impr
[
5481­
338]
10.5
g
of
product/

50­
100
cu.
ft
Contamination
of
water,
food
or
foodstuffs,
milk
or
milking
equipment
is
prohibited.
Use
of
product
where
unwrapped
food
is
stored
or
allowing
the
strip
to
come
in
contact
with
food
or
cooking
utensils
is
prohibited.

20%
Impr
[
5481­
344]

[
5481­
348]
10.5
g
of
product/

50­
100
cu.
ft
Contamination
of
water,
food
or
foodstuffs,
milk
or
milking
equipment
is
prohibited.

Milk
rooms
(
including
bulk
storage
rooms)

Premise
treatment
20%
Impr
[
5481­
338]
10.5
g
of
product/

50­
100
cu.
ft
Contamination
of
milk
or
milking
equipment
is
prohibited.
Use
of
product
where
unwrapped
food
is
stored
or
allowing
the
strip
to
come
in
contact
with
food
or
cooking
utensils
is
prohibited.

20%
Impr
[
5481­
344]

[
5481­
348]
10.5
g
of
product/

50­
100
cu.
ft
Contamination
of
milk
or
milking
equipment
is
prohibited.

Feed
lots,
stockyards,
corrals,
and
holding
pens
Outdoor
premise
treatment
1
lb/
gal
EC
[
5481­
41]
0.5%
finished
spray
[
5
gal/
A]
Applications
may
be
made
as
an
overall
mist
spray
to
fences,
feed
bunkers,
shade
areas,

spillage
areas,
building
walls,
and
other
areas
where
flies
congregate.
Applications
may
be
made
in
water
using
a
mist
blower
or
similar
equipment
at
3­
to
14­
day
intervals.
Page
21
of
151
Table
2.1.
Food/
Feed
Use
Patterns
on
EP
Labels
Subject
to
Reregistration
for
Dichlorvos
(
Case
0310).

Site
Application
Type
Formulation
[
EPA
Reg.

No.]
Application
Rate,
ai
1
Use
Directions
and
Limitations
2
0.37
lb/
gal
EC
[
5481­
220]

1.16
lb/
gal
EC
[
5481­
208]

1.59
lb/
gal
EC
[
5481­
206]

2
lb/
gal
EC
[
5481­
205]

4
lb/
gal
EC
[
5481­
204]

1.15
lb/
gal
SC
[
5481­
207]

4.48
lb/
gal
SC
[
5481­
202]

8.39
lb/
gal
SC
[
5481­
201]

10
lb/
gal
SC
[
5481­
200]
0.2
lb/
A
Applications
may
be
made
as
an
overall
mist
spray
to
fences,
feed
bunkers,
spillage
areas,

and
building
walls.
Applications
may
be
made
in
diesel
oil
or
water
using
a
mist
blower
or
similar
equipment.
Animals
may
be
present
during
treatment.

Poultry
houses
Page
22
of
151
Table
2.1.
Food/
Feed
Use
Patterns
on
EP
Labels
Subject
to
Reregistration
for
Dichlorvos
(
Case
0310).

Site
Application
Type
Formulation
[
EPA
Reg.

No.]
Application
Rate,
ai
1
Use
Directions
and
Limitations
2
Premise
treatment
0.37
lb/
gal
EC
[
5481­
220]

1
lb/
gal
EC
[
5481­
41]

1.16
lb/
gal
EC
[
5481­
208]

1.59
lb/
gal
EC
[
5481­
206]

2
lb/
gal
EC
[
5481­
73]

[
5481­
205]

4
lb/
gal
EC
[
5481­
204]

1.15
lb/
gal
SC
[
5481­
207]

4.48
lb/
gal
SC
[
5481­
202]

8.39
lb/
gal
SC
[
5481­
201]

10
lb/
gal
SC
[
5481­
200]
0.5%
finished
spray
[
1
qt/
1,000
sq.
ft]

Not
specified
on
the
2
lb/
gal
EC
[
5481­
73]

product
label
Applications
may
be
made
to
manure,
window
sills,
exterior
walls,
interior
walls,
feed
room
floors,
and
walkways.
Only
crack
and
crevice
treatments
are
permitted
for
indoor
use
and
applications
are
to
be
made
out
of
reach
of
poultry
(
EPA
Reg.
No.
5481­
41
only).

1%
G
[
5481­
9]
0.04
oz/
1,000
sq.
ft
Bait
applications
may
be
made
to
droppings
under
cages,
on
walkways,
window
sills,
alley
ways,
and
other
areas
where
flies
congregate.
Applications
are
to
be
made
out
of
reach
of
birds.
Page
23
of
151
Table
2.1.
Food/
Feed
Use
Patterns
on
EP
Labels
Subject
to
Reregistration
for
Dichlorvos
(
Case
0310).

Site
Application
Type
Formulation
[
EPA
Reg.

No.]
Application
Rate,
ai
1
Use
Directions
and
Limitations
2
Direct
Animal
Uses
Cattle
(
beef
and
dairy)

Animal
mist
spray
treatment
1
lb/
gal
EC
[
5481­
41]
1%
finished
spray
[
2
fl.
oz/
animal/
day]
Application
may
be
made
in
water
as
an
atomized
spray
uniformly
distributed
over
each
animal.
Do
not
wet
the
skin.

2
lb/
gal
EC
[
5481­
73]
0.5%
finished
spray
[
4
fl.
oz/
animal/
day]
Application
may
be
made
in
water
as
an
atomized
spray
uniformly
distributed
over
each
animal.
Application
more
than
once
per
day
and
application
to
calves
less
than
6
months
of
age
are
prohibited.
Page
24
of
151
Table
2.1.
Food/
Feed
Use
Patterns
on
EP
Labels
Subject
to
Reregistration
for
Dichlorvos
(
Case
0310).

Site
Application
Type
Formulation
[
EPA
Reg.

No.]
Application
Rate,
ai
1
Use
Directions
and
Limitations
2
0.37
lb/
gal
EC
[
5481­
220]

1.16
lb/
gal
EC
[
5481­
208]

1.59
lb/
gal
EC
[
5481­
206]

2
lb/
gal
EC
[
5481­
205]

4
lb/
gal
EC
[
5481­
204]

1.15
lb/
gal
SC
[
5481­
207]

4.48
lb/
gal
SC
[
5481­
202]

8.39
lb/
gal
SC
[
5481­
201]

10
lb/
gal
SC
[
5481­
200]
1%
finished
spray
[
2
fl.
oz/
animal/
day]
Application
may
be
made
in
deodorized
base
oil
or
water
as
an
atomized
spray
uniformly
distributed
over
each
animal.
Do
not
wet
the
hide.
Application
of
more
than
2
fl.
oz.
per
animal
per
day
and
application
to
calves
less
than
6
months
of
age
are
prohibited.
A
1­
day
PSI
has
been
established
(
EPA
Reg.
Nos.
5481­
204
and
5481­
220
only).

Cattle
(
beef
and
dairy)
(
continued)

Animal
face
paint
treatment
1
lb/
gal
EC
[
5481­
41]
0.5%
bait
slurry
[
1
tsp/
face]
Applications
may
be
made
to
the
animal's
forehead
daily
for
14
days
and
thereafter
as
needed.
Page
25
of
151
Table
2.1.
Food/
Feed
Use
Patterns
on
EP
Labels
Subject
to
Reregistration
for
Dichlorvos
(
Case
0310).

Site
Application
Type
Formulation
[
EPA
Reg.

No.]
Application
Rate,
ai
1
Use
Directions
and
Limitations
2
0.37
lb/
gal
[
5481­
220]

1.16
lb/
gal
EC
[
5481­
208]

1.59
lb/
gal
EC
[
5481­
206]

2
lb/
gal
EC
[
5481­
205]

4
lb/
gal
EC
[
5481­
204]

1.15
lb/
gal
SC
[
5481­
207]

4.48
lb/
gal
SC
[
5481­
202]

8.39
lb/
gal
SC
[
5481­
201]

10
lb/
gal
SC
[
5481­
200]
1%
bait
slurry
[
3
mL/
face]
Application
is
to
be
made
as
a
6­
inch
line
to
the
animal's
forehead
with
a
paint
brush.

Cattle
(
beef
and
dairy)
(
continued)
Page
26
of
151
Table
2.1.
Food/
Feed
Use
Patterns
on
EP
Labels
Subject
to
Reregistration
for
Dichlorvos
(
Case
0310).

Site
Application
Type
Formulation
[
EPA
Reg.

No.]
Application
Rate,
ai
1
Use
Directions
and
Limitations
2
Manure
treatment
0.37
lb/
gal
EC
[
5481­
220]

1
lb/
gal
EC
[
5481­
41]

1.16
lb/
gal
EC
[
5481­
208]

1.59
lb/
gal
EC
[
5481­
206]

2
lb/
gal
EC
[
5481­
73]

[
5481­
205]

4
lb/
gal
EC
[
5481­
204]

1.15
lb/
gal
SC
[
5481­
207]

4.48
lb/
gal
SC
[
5481­
202]

8.39
lb/
gal
SC
[
5481­
201]

10
lb/
gal
SC
[
5481­
200]
0.5%
finished
spray
[
2
qt/
100
sq.
ft]

or
1%
finished
spray
[
1
qt/
100
sq.
ft]
Applications
may
be
made
in
water
to
control
maggots
in
manure
piles
and
garbage
dumps.

Poultry
Page
27
of
151
Table
2.1.
Food/
Feed
Use
Patterns
on
EP
Labels
Subject
to
Reregistration
for
Dichlorvos
(
Case
0310).

Site
Application
Type
Formulation
[
EPA
Reg.

No.]
Application
Rate,
ai
1
Use
Directions
and
Limitations
2
Manure
treatment
1
lb/
gal
EC
[
5481­
41]
0.5%
finished
spray
[
2
qt/
100
sq.
ft]
Applications
may
be
made
in
diesel
oil
or
deodorized
kerosene
to
control
flies
and
maggots
in
poultry
droppings.

Animal
Uses
­
Oral
Dosing
(
Drug
Use)

Swine
Feed
treatment
N/
A
3
12.5­
20.6
mg/
kg
body
weight
Application
is
to
be
made
by
mixing
active
ingredient
into
feed
and
may
be
repeated
in
4­
5
weeks.

Wide
Area
and
General
Outdoor
Treatment
Outdoor
areas
(
including
outside
picnic
areas,
patios,
and
eating
areas
of
drive­
in
restaurants)

Outdoor
spray
application
2
lb/
gal
SC
[
5481­
334]
0.5­
1%
finished
spray
Applications
may
be
made
in
deodorized
spray
base
oil
and
repeated
monthly
or
as
needed.

Outdoor
areas
(
including
picnic
grounds,
parking
areas,
loading
docks,
refuse
areas,
garbage
collection
and
disposal
areas,
around
drive­
in
restaurants,
food
processing
plants,
and
warehouses)

Outdoor
spray
application
1
lb/
gal
EC
[
5481­
41]
0.5%
finished
spray
[
1
qt/
1,000
sq.
ft]
Applications
may
be
made
in
water
and
repeated
as
needed.
Direct
use
on
animals
and
contamination
of
feed,
foodstuffs,
or
water
are
prohibited.

Outdoor
areas
(
including
picnic
grounds,
parking
areas,
loading
docks,
refuse
areas,
garbage
collection
and
disposal
areas,
around
drive­
in
restaurants,
food
processing
plants,
and
warehouses)
(
continued)
Page
28
of
151
Table
2.1.
Food/
Feed
Use
Patterns
on
EP
Labels
Subject
to
Reregistration
for
Dichlorvos
(
Case
0310).

Site
Application
Type
Formulation
[
EPA
Reg.

No.]
Application
Rate,
ai
1
Use
Directions
and
Limitations
2
Outdoor
spray
application
0.37
lb/
gal
EC
[
5481­
220]

1.16
lb/
gal
EC
[
5481­
208]

1.59
lb/
gal
EC
[
5481­
206]

2
lb/
gal
EC
[
5481­
205]

4
lb/
gal
EC
[
5481­
204]

1.15
lb/
gal
SC
[
5481­
207]

4.48
lb/
gal
SC
[
5481­
202]

8.39
lb/
gal
SC
[
5481­
201]

10
lb/
gal
SC
[
5481­
200]
0.5%
finished
spray
[
1
qt/
1,000
sq.
ft]
Applications
may
be
made
in
diesel
oil
or
water
and
repeated
as
needed.
Direct
use
on
animals
or
humans
and
contamination
of
water,
food,
food
containers
or
cooking
utensils
are
prohibited.

Outdoor
areas
(
including
picnic
grounds,
parking
areas,
loading
docks,
refuse
areas,
garbage
collection
and
disposal
areas,
around
drive­
in
restaurants,
food
processing
plants,
and
warehouses)
(
continued)
Page
29
of
151
Table
2.1.
Food/
Feed
Use
Patterns
on
EP
Labels
Subject
to
Reregistration
for
Dichlorvos
(
Case
0310).

Site
Application
Type
Formulation
[
EPA
Reg.

No.]
Application
Rate,
ai
1
Use
Directions
and
Limitations
2
Outdoor
fogging
application
[
Hand­
Held
Foggers
are
no
longer
permitted]
0.37
lb/
gal
EC
[
5481­
220]

1.16
lb/
gal
EC
[
5481­
208]

1.59
lb/
gal
EC
[
5481­
206]

2
lb/
gal
EC
[
5481­
205]

4
lb/
gal
EC
[
5481­
204]

1.15
lb/
gal
SC
[
5481­
207]

4.48
lb/
gal
SC
[
5481­
202]

8.39
lb/
gal
SC
[
5481­
201]

10
lb/
gal
SC
[
5481­
200]
1%
finished
spray
[
5­
10
pt/
A]

or
0.05­
0.1
lb/
A
Fogging
or
misting
applications
may
be
made
with
diesel
oil
or
water
using
fogging
or
misting
equipment
to
treat
outdoor
living
areas,
picnic
areas,
backyard
areas,
patios,

loading
docks,
outdoor
latrines,
parking
areas,
refuse
areas
around
service
stations,
open
air
drive­
ins,
ice
cream
stands,
and
garbage
collection
and
disposal
areas.
Use
in
areas
where
food
or
feed
crops
are
growing
is
prohibited.

Catch
basins
Outdoor
treatment
20%
Impr
[
5481­
338]

[
5481­
344]

[
5481­
348]
One
strip
One
strip
(
10.5
or
80
g
of
product)
is
to
be
suspended
10
inches
above
water
level
for
control
of
mosquitoes
breeding
in
catch
basins.
Page
30
of
151
1
Application
rates
in
brackets
refer
to
amount
of
finished
spray
to
be
applied
per
listed
area.

2
The
product
label
for
EPA
Reg.
No.
5481­
41
prohibits
treatment
of
more
than
5
application
sites
per
day
and
prohibits
DDVP
applications
more
than
once
per
week
(
we
note
that
this
is
in
conflict
with
use
directions
for
feedlots,
stockyards,
corrals,
and
holding
pens
which
allow
applications
to
be
made
at
3­
day
intervals).
A
similar
statement
was
required
to
be
added
to
the
product
label
for
EPA
Reg.
No.
5481­
200.
No
other
products
listed
in
this
table
bear
this
restriction.

3
DDVP
is
registered
for
use
as
an
anthelmintic
in
swine
feed;
use
pattern
is
defined
in
21
CFR
§
520.600(
e)(
2).
Page
31
of
151
2.2
Structure
and
Nomenclature
TABLE
2.2.
Test
Compound
Nomenclature
Chemical
Structure
P
O
O
H
3
CO
OCH
3
Cl
Cl
Empirical
Formula
C4H7Cl2O4P
Common
name
Dichlorvos
(
ISO)
or
DDVP
Company
experimental
name
IUPAC
name
2,2­
dichlorovinyl
dimethyl
phosphate
CAS
name
2,2­
dichloroethenyl
dimethyl
phosphate
CAS
Registry
Number
62­
73­
7
End­
use
product/
EP
Alco,
Amvos
Chemical
Class
organophosphate
Known
Impurities
of
Concern
none
PC
Code
No.
084001
2.3
Physical
and
Chemical
Properties
Dichlorvos
is
a
liquid
with
high
vapor
pressure
at
room
temperature
and
is
used
for
fumigation.
The
high
vapor
pressure
suggests
that
residues
in
food
and
environmental
surfaces
will
dissipate
rapidly.
Page
32
of
151
TABLE
2.3.
Physicochemical
Properties
Parameter
Value
Reference
Molecular
Weight
221.0
Physical
State
l
iquid
40798103
Boiling
point/
range
117
C
at
10
mm
Hg
40798103
pH
~
4
as
1%
aqueous
solution
40798103
Specific
gravity
1.424
at
25
C
40798103
Water
solubility
(
20
C)
~
1.5
g/
100
g
40798103
Solvent
solubility
(
temperature
not
specified)
~
0.5%
in
glycerine;
miscible
with
aromatic
hydrocarbons,
chlorinated
hydrocarbons,
alcohols,
ketones,
and
esters.
Essentially
insoluble
in
kerosene
and
aliphatic
hydrocarbons
40798103
Vapor
pressure
(
25
C)
0.032
mm
Hg
at
32
C
40798103
Dissociation
constant,
pKa
N/
A
Octanol/
water
partition
coefficient,
log
KOW
(
25
C)
38.4
log
KOW
=
1.58
40798103
UV/
visible
absorption
spectrum
N/
A
Page
33
of
151
3.0
Metabolism
Assessment
3.1
Comparative
Metabolic
Profile
A
rat
metabolism
study
has
been
conducted.
The
overall
metabolic
profile
suggests
the
involvement
of
the
one­
carbon
pool
biosynthetic
pathway
as
evidenced
by
the
presence
of
a
relatively
large
amount
of
radioactivity
in
the
form
of
expired
14CO2
and
the
presence
of
dehalogenated
metabolites
as
well
as
urea
and
hippuric
acid.
Plant
metabolism
studies
show
that
dichlorvos
hydrolyzes
to
dimethyl
phosphate
and
dichloroacetaldehyde,
and
is
incorporated
into
natural
plant
constituents.
Oral
and
dermal
livestock
metabolism
studies
show
that
dichlorvos
metabolizes
to
desmethyl
dichlorvos
in
livestock
animals.
The
major
environmental
degradates
were
2,2­
dichloroacetic
acid,
2,2­
dichloroacetaldehyde,
desmethyl
dichlorvos,
and
glyoxylic
acid.

3.2
Nature
of
the
Residue
in
Foods
3.2.1.
Description
of
Primary
Crop
Metabolism
Nature
of
the
Residue
­
Plants
(
GLN
860.1300):
The
reregistration
requirements
for
plant
metabolism
are
fulfilled.
The
Agency
determined
that
the
available
data
depicting
the
metabolism
of
naled
in
plants
are
sufficient
to
delineate
the
metabolism
of
dichlorvos
in
plants
because
dichlorvos
is
the
initial
metabolite
of
naled.
In
plants,
naled
is
metabolized
to
dichlorvos
which
is
hydrolyzed
to
dimethyl
phosphate
and
dichloroacetaldehyde.
Dimethyl
phosphate
is
sequentially
degraded
to
monomethyl
phosphate
and
inorganic
phosphates,
and
dichloroacetaldehyde
is
converted
to
2,2­
dichloroethanol
which
is
then
conjugated
and/
or
incorporated
into
naturally
occurring
plant
components.
The
residue
of
concern
in
plant
commodities
is
dichlorvos.

3.2.2
Description
of
Livestock
Metabolism
Nature
of
the
Residue
­
Animals
(
GLN
860.1300):
The
reregistration
requirements
for
animal
metabolism
are
fulfilled.
Acceptable
studies
depicting
the
qualitative
nature
of
the
residue
in
ruminants
and
poultry
following
dermal
treatment
with
dichlorvos
have
been
submitted
and
evaluated.
Because
dichlorvos
is
the
initial
metabolite
of
naled,
the
available
metabolism
studies
reflecting
oral
dosing
of
ruminants
and
hens
with
naled
are
sufficient
to
delineate
the
metabolism
of
orally
dosed
dichlorvos
in
animals.
The
residue
of
concern
in
animal
commodities
is
dichlorvos.

In
the
lactating
goat
treated
orally
with
naled,
no
naled
or
dichlorvos
was
identified
in
milk
(<
0.005
ppm)
or
tissues
(<
0.05
ppm).
Dichloroethanol
conjugates
and
desmethyl­
dichlorvos
were
not
identified
in
milk
(<
0.05
ppm).
Liver
and
kidney
contained
up
to
0.3
ppm
dichloroethanol
conjugates
and
0.1
ppm
desmethyl­
dichlorvos;
other
tissues
showed
only
traces
of
both
of
these
metabolites.
Page
34
of
151
In
laying
hens
treated
orally
with
naled,
the
sulfate
conjugate
of
dichloroethanol
was
the
major
component
(
0.1
ppm
in
fat
to
10
ppm
in
kidney)
identified
in
all
tissues.
The
parent
compound,
naled,
was
not
identified
(<
0.01
ppm)
in
any
tissues
except
gizzard.
Naled
plus
mostly
dichlorvos
were
found
in
gizzard
(
0.6
ppm)
after
2
hours
in
singly
dosed
hens
and
as
a
minor
metabolite
(
0.01­
0.46
ppm)
in
tissue
samples
of
multi­
dosed
hens.

In
both
lactating
goats
and
laying
hens
treated
orally
with
naled,
naled
is
initially
debrominated
to
yield
dichlorvos.
The
major
pathway
is
cleavage
of
dichlorvos
to
dimethylphosphate
and
dichloroacetaldehyde.
A
minor
pathway
is
O­
demethylation
to
form
desmethyl­
dichlorvos.
In
part,
dichloroacetaldehyde
is
reduced
to
dichloroethanol
which
is
conjugated
with
endogenous
sulfate
to
form
the
sulfate
ester
conjugate
of
dichloroethanol.
Dichloroacetaldehyde
is
dechlorinated
and
oxidized
sequentially
to
form
glyoxal
and
then
glyoxylic
acid
which
is
incorporated
into
amino
acids
(
glycine,
alanine,
serine,
etc.)
and
proteins.

Metabolism
of
dichlorvos
in
ruminants,
following
dermal
exposure,
is
adequately
understood.
Dichlorvos
is
extensively
metabolized
following
dermal
exposure.
No
dichlorvos
or
primary
metabolites
of
dichlorvos
were
found
in
milk
or
tissues
of
treated
goats,
furthermore,
incorporation
of
14C
into
endogenous
milk
(
as
lactose)
and
tissue
components
(
as
glycerol)
of
the
treated
goats
was
demonstrated.

Metabolism
of
dichlorvos
in
poultry,
following
dermal
exposure,
is
adequately
understood.
Dichlorvos
is
extensively
metabolized
following
dermal
exposure.
Limited
amounts
of
dichlorvos
and
des­
methyl
dichlorvos
were
identified
in
breast
muscle
and
fat,
with
the
majority
of
the
TRR
incorporated
into
tissue.
Radioactivity
found
in
internal
tissues
accounted
for
0.3%
of
the
administered
dose.

3.2.3
Description
of
Rotational
Crop
Metabolism,
including
identification
of
major
metabolites
and
specific
routes
of
biotransformation
Dichlorvos
is
not
registered
for
field
crop
uses;
therefore
no
rotational
crop
data
have
been
required.

3.3
Environmental
Degradation
Dichlorvos.
A
major
route
of
dissipation
is
volatilization
(
vapor
pressure
=
0.032
mm
Hg
at
32
C).
Dichlorvos
also
appears
to
degrade
through
aerobic
soil
metabolism
and
abiotic
hydrolysis
as
well,
but
is
secondary
to
volatilization.
Hydrolysis
is
pH
dependant
where
the
half­
lives
were
11
days
at
pH
5,
5
days
at
pH
7
and
21
hours
at
pH
9.
The
major
degradates
were
2,2­
dichloroacetic
acid,
2,2­
dichloroacetaldehyde,
desmethyl
dichlorvos,
and
glyoxylic
acid.
Aerobic
soil
metabolism
data
showed
a
half­
life
of
10
hours
with
the
major
metabolite
being
2,2­
dichloroacetic
acid
(
62.8%
of
applied
at
48
hours).
Other
metabolites
present
at
less
than
12%
of
applied
were
2,2­
dichloroacetaldehyde,
and
dichloroethanol.
Extensive
mineralization
took
place
as
CO2
accounted
for
60%
of
applied
at
360
hours
post­
treatment.
Due
to
rapid
degradation
of
dichlorvos
leaching/
adsorption/
desorption
data
were
declared
supplemental
due
to
the
inability
to
establish
a
soil/
solution
phase
equilibrium.
However,
a
soil
TLC
study
(
MRID
41354105)
indicates
that
dichlorvos
is
moderately
mobile
(
Kd's
ranging
0.3
to
1.2)
based
on
the
Page
35
of
151
Heiling
and
Turner's
mobility
classification.
The
potential
of
dichlorvos
to
leach
to
ground
water
is
mitigated
by
its
rapid
degradation.
However,
dichlorvos
does
have
the
potential
to
contaminate
surface
waters
because
of
a
low
Koc
value
and
high
water
solubility
(
10
X
103
ppm,
or
1%).
Substantial
fractions
of
run­
off
will
more
than
likely
occur
via
dissolution
in
run­
off
water
rather
than
adsorption
to
eroding
soil.
Dichlorvos
should
not
be
persistent
in
any
surface
waters
due
to
its
susceptibility
to
rapid
hydrolysis.

Naled.
Chemical
hydrolysis
and
biodegradation
are
the
major
processes
involved
in
the
transformation
of
naled
and
its
degradates
in
the
environment.
While
direct
photolysis
in
water
is
not
a
major
degradative
pathway
for
naled,
indirect
photolysis
in
the
presence
of
photosensitizer
may
play
an
important
role
in
the
photodegradation
of
naled
in
aqueous
media
and
soils.
The
degradate
dichlorvos
does
not
form
under
abiotic
hydrolysis
nor
by
direct
photolysis
in
water,
but
forms
by
indirect
photolysis
in
water
and
soils.
In
the
presence
of
photosensitizer
in
water,
as
much
as
20%
of
the
applied
dose
of
naled
can
be
found
as
dichlorvos
after
1
day,
with
rapid
decline
of
dichlorvos
residues
afterwards.
Under
aerobic
conditions,
naled
mineralizes
rapidly
to
CO2
and
degrades
to
dichloroacetic
acid
and
dichloroethanol,
but
dichlorvos
is
not
detected.
This
is
likely
to
be
the
result
of
the
rapid
degradation
and
mineralization
of
any
dichlorvos
that
may
form
from
naled.
However,
under
anaerobic
aquatic
conditions,
dichlorvos
can
be
as
high
as
15%
of
the
applied
naled
dose
after
1
day.
The
degradation
of
dichlorvos,
once
formed,
was
slower
than
that
of
parent
naled.
During
the
first
1­
2
days
after
application
of
naled,
the
half­
life
of
dichlorvos
was
about
0.9
days.

Trichlorfon.
Dichlorvos
is
formed
from
trichlorfon
in
both
soil
and
water
by
aerobic
soil
metabolism.
Environmental
fate
data
indicate
that
trichlorfon
degrades
rapidly
in
aerobic
soil
(
t1/
2
1.8
days)
under
non­
sterile
conditions;
however,
in
a
sterile
soil,
trichlorfon
was
stable
(
t1/
2
>
40
days).
Abiotic
hydrolysis
studies
indicate
that
trichlorfon
degrades
rapidly
in
aqueous
media
and
that
the
rate
of
conversion
is
pH
dependent.
The
estimated
half­
life
of
trichlorfon
is
31
minutes
at
pH
9,
and
34
hours
at
pH
7,
and
104
days
at
pH
5.
This
indicates
the
stability
of
trichlorfon
under
acidic
conditions.
The
maximum
amount
of
dichlorvos
formed
from
trichlorfon
by
aerobic
aquatic
metabolism
is
approximately
56
percent
of
the
amount
of
trichlorfon
originally
applied
at
pH
8.5.
Page
36
of
151
3.4
Summary
of
Residues
for
Tolerance
Expression
and
Risk
Assessment
Tolerances
for
residues
of
dichlorvos
are
published
in
40
CFR
180.235.
The
current
tolerance
expression
includes
only
dichlorvos
[
2,2­
dichlorovinyl
dimethyl
phosphate].

Table
3.6.
Summary
of
Metabolites
and
Degradates
to
be
included
in
the
Risk
Assessment
and
Tolerance
Expression
Matrix
Residues
included
in
Risk
Assessment
Residues
included
in
Tolerance
Expression
Primary
Crop
dichlorvos
dichlorvos
Plants
Rotational
Crop
N/
A
N/
A
Ruminant
dichlorvos
dichlorvos
Livestock
Poultry
dichlorvos
dichlorvos
Drinking
Water
dichlorvos
Not
Applicable
4.0
Hazard
Characterization/
Assessment
4.1
Hazard
Characterization
Dichlorvos
is
a
chlorinated
organophosphate
pesticide
cholinesterase
inhibitor,
which
inhibits
plasma,
erythrocyte,
and
brain
cholinesterase
in
a
variety
of
species,
but
does
not
cause
organophosphate­
induced
delayed
neurotoxicity
(
OPIDN)
in
the
hen.
Concern
for
potential
developmental
neurotoxicity
arose
based
on
a
study
in
the
open
literature
(
Mehl
et
al,
1994),
which
reported
decreased
total
brain
weight
in
two
litters
of
guinea
pigs
from
dichlorvos­
exposed
dams.
However,
in
developmental
neurotoxicity
studies
in
rats,
decreased
brain
weight
was
not
associated
with
gavage
doses
of
dichlorvos
administered
to
pups
during
PNDs
8­
22.
In
acute
and
90­
day
neurotoxicity
studies
in
rats,
there
was
no
neuropathology
associated
with
changes
in
FOB
and
motor
activity.
Subchronic
and
chronic
oral
exposures
in
rats
and
dogs
as
well
as
chronic
inhalation
exposure
in
rats
resulted
in
significant
decreases
in
plasma,
red
blood
cell
and/
or
brain
cholinesterase
activity.
Repeated,
oral
subchronic
exposures
in
male
humans
were
associated
with
statistically
and
biologically
significant
decreases
in
red
blood
cell
cholinesterase
depression.

There
was
no
evidence
of
increased
susceptibility
following
in
utero
exposure
to
rats
and
rabbits
as
well
as
pre/
post
natal
exposure
to
rats
in
developmental
and
reproduction
studies.
The
FQPA
safety
factor
was
reduced
to
1x.
Some
scenarios
used
endpoints
based
on
a
LOAEL,
and
the
3x
uncertainty
factor
used
is
considered
part
of
the
FQPA
safety
factor.

The
carcinogenic
potential
of
dichlorvos
has
been
classified
as
"
suggestive"
under
the
1999
Draft
Cancer
Guidelines
and
no
quantitative
assessment
of
cancer
risk
is
required.
Dichlorvos
has
been
shown
to
be
a
direct
acting
mutagen
in
in
vitro
mammalian
test
systems.
Dichlorvos
seems
to
also
have
clastogenic
activity
in
Chinese
hamster
ovary
(
CHO)
cells
in
vitro
with
or
without
metabolic
activation.
On
the
other
hand,
studies
showed
that
dichlorvos
was
not
clastogenic
in
in
vivo
micronucleus
tests.
Page
37
of
151
Inhibition
of
cholinesterase
activity
was
the
toxicity
endpoint
selected
to
assess
hazards
for
all
acute
and
chronic
dietary
reference
doses
(
RfDs),
as
well
as
short­,
intermediate­,
and
long­
term
(
chronic)
dermal
and
inhalation
occupational
and
residential
risk
assessments.
The
no
observed
adverse
effect
levels
(
NOAELs),
lowest
observed
adverse
effect
levels
(
LOAELs),
or
BMDL10s
were
selected
in
light
of
Agency
policy
on
the
use
of
toxicology
studies
employing
human
subjects.
Therefore,
HED
selected
doses
and
endpoints
for
risk
assessment
based
on
both
human
and
animal
studies.

Table
4.1a
Acute
Toxicity
of
Dichlorvos
Guideline
No.
Study
Type
MRID
#(
S).
Results
Toxicity
Category
8701.1100
Acute
Oral
00005467
LD50
=
80
mg/
kg
(
M)
56
mg/
kg
(
F)
II
870.1200
Acute
Dermal
00005467
LD50
=
107
mg/
kg
(
M)
>
75
mg/
kg
(
F)
I
870.1300
Acute
Inhalation
00137239
LC50>
0.198
mg/
L
II
870.2400
Primary
Eye
Irritation
00146921
mild
irritant
III
870.2500
Primary
Skin
Irritation
00146920
mild
irritant
IV
870.2800
Dermal
Sensitization
none
no
study
available
NA
870.6100
Acute
Delayed
Neurotoxicity­
Hen
41004702
Negative
for
acute
delayed
neurotoxicity
NA
870.6200
Acute
Neurotoxicity­
Rat
42655301
NOAEL
=
0.5
mg/
kg;
LOAEL
=
35
mg/
kg
(
changes
in
FOB,
motor
activity
)
no
neuropathology
NA
Page
38
of
151
Table
4.1b.
Guideline
Toxicology
Studies
for
Dichlorvos
in
Experimental
Animals
Guideline
No./
Study
Type
MRID
No.
Results
Acute
Oral
Cholinesterase
Inhibition
Study
(
1
st
)
in
Adult
SD
Rats/
870.1100
(
non­
guideline)
45805701
Acceptable
ChEI
NOAEL
(
RBC
and
Brain)
=
not
established
ChEI
LOAEL
(
RBC
and
Brain)
=
2.1
mg/
kg/
day
Acute
Oral
Cholinesterase
Inhibition
Study
(
2
nd
)
in
Adult
SD
Rats/
870.1100
(
non­
guideline)
45805702
Acceptable
ChEI
NOAEL
(
RBC
and
Brain)
=
1
mg/
kg
ChEI
LOAEL
(
RBC
and
Brain)
=
not
established
Acute
Oral
Cholinesterase
Inhibition
Study
(
3
rd
)
in
Adult
Wistar
Rats/
870.1100
(
non­
guideline)
45805703
Acceptable
RBC
Cholinesterase
Inhibition
NOAEL
=
1
mg/
kg
LOAEL
=
5
mg/
kg
BMD/
BMDL10
=
1.7/
1.3
(
M)
mg/
kg
BMD/
BMDL10
=
1.5/
1.2
(
F)
mg/
kg
Brain
Cholinesterase
Inhibition
NOAEL
=
1
mg/
kg
LOAEL
=
5
mg/
kg
BMD/
BMDL10
=
1.6/
1.0
(
M)
mg/
kg
BMD/
BMDL10
=
1.6/
0.8
(
F)
mg/
kg
Acute
Oral
Cholinesterase
Inhibition
Study
in
Preweaning
Wistar
Rat
Pups/
870.1100
(
non­
guideline)
45842301
Acceptable
RBC
Cholinesterase
Inhibition
ChEI
NOAEL
(
RBC)
=
not
established
ChEI
LOAEL
(
RBC)
=
1
mg/
kg
Postnatal
day
8
BMD/
BMDL10
=
1.8/
1.3
(
M)
mg/
kg;
Postnatal
day
8
BMD/
BMDL10
=
1.5/
1.0
(
F)
mg/
kg;

Brain
Cholinesterase
Inhibition
ChEI
NOAEL
(
Brain)
=
1
mg/
kg
ChEI
NOAEL
(
Brain)
=
5
mg/
kg
Postnatal
day
8
BMD/
BMDL10
=
1.8/
1.5
(
M)
mg/
kg;
Postnatal
day
8
BMD/
BMDL10
=
2.2/
1.6
(
F)
mg/
kg;

Time
Course
of
Cholinesterase
Inhibition
in
Preweaning
and
Adult
Wistar
Rats/
870.8223
(
Non­
Guideline)
46153303
Acceptable
Brain
and
RBC
enzyme
activities
were
maximally
inhibited
one
hour
after
single
dosing
in
both
adult
and
preweaning
female
rats.
Thereafter,
ChE
inhibition
in
both
compartments
decreased
to
approximately
control
levels
by
8
hours
post
dosing.

Repeat
Dose
Cholinesterase
Inhibition
Study
in
Preweaning
(
PND
18)
and
Adult
(
PND
48)
Wistar
Rats/(
Non­
Guideline)
46153304
Acceptable
PND18
BMD
/
BMDL10=
1.41/
1.66
mg/
kg/
d
RBC
ChEI
(
M)
PND48
BMD
/
BMDL10=
1.31/
1.63
mg/
kg/
d
RBC
ChEI
(
M)
PND18
BMD
/
BMDL10=
0.83/
1.47
mg/
kg/
d
RBC
ChEI
(
F)
PND48
BMD
/
BMDL10=
1.26/
1.55
mg/
kg/
d
RBC
ChEI
(
F)
PND18
BMD
/
BMDL10=
1.40/
1.50
mg/
kg/
d
Brain
ChEI
(
M)
PND48
BMD
/
BMDL10=
0.76/
1.46
mg/
kg/
d
Brain
ChEI
(
M)
PND18
BMD
/
BMDL10=
1.80/
2.02
mg/
kg/
d
Brain
ChEI
(
F)
PND48
BMD
/
BMDL10=
1.26/
1.55
mg/
kg/
d
Brain
ChEI
(
F)

Dichlorvos:
A
single
blind,
placebo
controlled,
randomized
study
to
investigate
the
effects
of
multiple
oral
dosing
on
erythrocyte
cholinesterase
inhibition
in
healthy
male
volunteers
(
non­
guideline)
44248801
Acceptable
RBC
cholinesterase
inhibition
LOAEL
=
0.1
mg/
kg/
day
NOAEL
=
not
established
Page
39
of
151
Table
4.1b.
Guideline
Toxicology
Studies
for
Dichlorvos
in
Experimental
Animals
Guideline
No./
Study
Type
MRID
No.
Results
Dichlorvos:
A
study
to
investigate
erythrocyte
cholinesterase
inhibition
following
oral
administration
to
healthy
male
volunteers
(
non­
guideline)
44317901
Unacceptable
RBC
cholinesterase
inhibition
NOAEL
=
not
determined
(
missed
time
of
peak
effect)

Dichlorvos:
A
study
to
investigate
the
effect
of
a
single
oral
dose
on
erythrocyte
cholinesterase
inhibition
in
healthy
male
volunteers
(
nonguideline
44248802
Unacceptable
RBC
cholinesterase
inhibition
NOAEL
=
not
determined
(
missed
time
of
peak
effect)

Dermal
Absorption/
870.7600
41435201
Acceptable
Dermal
absorption
rate
for
dichlorvos
was
estimated
to
be
approximately
11%
in
10
hours
of
exposure.

28­
Day
Delayed
Neurotoxicity­
Hen/
870.6100
43433501
Acceptable
Cholinesterase
inhibition
(
brain
ChEI)
NOAEL
=
0.1
mg/
kg/
day
LOAEL
=
0.3
mg/
kg/
day
No
neuropathology.

90­
Day
Subchronic
Oral
Toxicity
­
Rat/
870.3100
41004701
Acceptable
NOAEL
=
0.1
mg/
kg/
day
LOAEL
=
1.5
mg/
kg/
day
(
plasma
and
RBC
ChEI)

90­
Day
Neurotoxicity
­
Rat/
870.6200
42958101
Acceptable
NOAEL
=
0.1
mg/
day
LOAEL
=
7.5
mg/
kg/
day
(
plasma,
red
blood
cell
(
RBC)
and
brain
ChEI).

Chronic­
Feeding­
Dog/
870.4100
41593101
Acceptable
NOAEL
=
0.05
mg/
kg/
day
LOAEL
=
0.1
mg/
kg/
day
(
plasma
and
RBC
ChEI
in
both
sexes).

2­
Year
Inhalation
toxicity/
carcinogenicity
­
Rat/
870.4200
00057695,
00632569
Acceptable
BMD/
BMDL10
=
0.15/
0.07
mg/
m
3
RBC
ChEI
(
F)
BMD/
BMDL10
=
0.14/
0.04
mg/
m
3
RBC
ChEI
(
M)
BMD/
BMDL10
=
0.29/
0.29
mg/
m
3
Brain
ChEI
(
F)
BMD/
BMDL10
=
0.31/
0.30
mg/
m
3
Brain
ChEI
(
M)

Chronic
toxicity/
Carcinogenicity­
F344
Rats
(
NTP
study)/
870.4300
40299401
Acceptable
NOAEL
=
Not
established
LOAEL
=
4.0mg/
kg/
day
(
plasma
and
RBC
ChEI)
Suggestive
evidence
of
carcinogenicity
(
mononuclear
cell
leukemia
in
male
rats)

Carcinogenicity­
Mouse/
870.4200
40299401
Acceptable
NOAEL
=
Not
established
LOAEL
=
10
mg/
kg/
day
(
plasma
and
RBC
ChEI
in
males)

Developmental
Toxicity­
Rat/
870.3700
41951501
Acceptable
Maternal
toxicity
NOAEL
=
3
mg/
kg/
day
LOAEL
=
21
mg/
kg/
day
(
clinical
signs,
decreased
body
weight
gain
and
reductions
in
food
consumption
and
efficiency)
Developmental
toxicity
NOAEL
=
>
21
mg/
kg/
day
(
HDT)
Page
40
of
151
Table
4.1b.
Guideline
Toxicology
Studies
for
Dichlorvos
in
Experimental
Animals
Guideline
No./
Study
Type
MRID
No.
Results
Developmental
Toxicity­
Rabbit/
870.3700
41802401
Acceptable
Maternal
toxicity
NOAEL
=
0.1
mg/
kg/
day
LOAEL
=
2.5
mg/
kg/
day
(
mortality,
decreased
body
weight
gain
at
LOAEL)

Developmental
toxicity
NOAEL=
>
7
mg/
kg/
day
(
HDT)
ChEI
was
not
measured
in
main
study
Range­
Finding:
Doses
were
0,
0.1,
1.0,
2.5,
5.0,
10
mg/
kg/
day
Maternal
toxicity
ChE
NOAEL
=
0.1
mg/
kg/
day
ChE
LOAEL
=
1.0
mg/
kg/
day
Reproductive
Toxicity
­
Rat/
870.3800
42483901
Acceptable
Parental/
Systemic
NOAEL
=
2.3
mg/
kg/
day
LOAEL
=
8.3
mg/
kg/
day
(
decreased
%
of
females
with
estrous
cycle
and
increased
%
of
females
with
abnormal
cycling)
Offspring
NOAEL
=
2.3
mg/
kg/
day
LOAEL
=
8.3
mg/
kg/
day
(
reduced
#
dams
bearing
litter,
fertility
index,
pregnancy
index
and
pup
weight).

Preliminary
Developmental
Neurotoxicity
­
Rat/(
Non­
Guideline)
46153301
Acceptable
Systemic
NOAEL
=
7.5
mg/
kg/
day
Maternal
Systemic
LOAEL
=
not
identified
Maternal
RBC
ChEI
NOAEL
=
0.1
mg/
kg/
day
Maternal
RBC
ChEI
LOAEL
=
1.0
mg/
kg/
day
Maternal
Brain
ChEI
NOAEL
=
1.0
mg/
kg/
day
Maternal
Brain
ChEI
LOAEL
=
7.5
mg/
kg/
day
Maternal
Systemic
NOAEL
=
7.5
mg/
kg/
day
Offspring
Systemic
LOAEL
=
not
identified
Offspring
RBC
ChEI
NOAEL
=
1.0
mg/
kg/
day
Fetuses
(
GD
22)
RBC
ChEI
LOAEL
=
7.5
mg/
kg/
day
Fetuses
(
GD
22)

Brain
ChEI
NOAEL
=
1.0
mg/
kg/
day
Fetuses
(
GD
22)
Brain
ChEI
LOAEL
=
7.5
mg/
kg/
day
Fetuses
(
GD22)

Offspring
(
Pups)
did
not
demonstrate
ChEI
during
PND
2­
22
Developmental
Neurotoxicity
­
Rat/
870.6300
46153302
Acceptable
(
Study
RR0886)
Maternal
toxicity
NOAEL
=
7.5
mg/
kg/
day
(
HDT)
No
treatment
related
effects
Developmental
toxicity
NOAEL=
1.0
mg/
kg/
day
LOAEL
=
7.5
mg/
kg/
day
(
increases
in
auditory
startle
reflex
habituation
Vmax
in
PND
23
high
dose
males
in
both
studies)
ChEI
was
not
measured
in
main
study
Page
41
of
151
Table
4.1b.
Guideline
Toxicology
Studies
for
Dichlorvos
in
Experimental
Animals
Guideline
No./
Study
Type
MRID
No.
Results
Developmental
Neurotoxicity
­
Rat/
870.6300
46239801
Acceptable
(
Study
RR0988)
Maternal
NOAEL
is
7.5
mg/
kg/
day
(
HDT).
A
maternal
LOAEL
was
not
established.

Offspring/
developmental
NOAEL
is
1.0
mg/
kg/
day
(
based
on
study
RR0886)
and
the
Offspring/
developmental
LOAEL
is
7.5
mg/
kg/
day
(
based
on
both
studies
RR0886
and
RR0988)
with
the
effect
being
increases
in
auditory
reflex
habituation
Vmax
in
PND
23
high
dose
males
in
both
studies.

Mutagenicity/
Genetic
Toxicity
Test
Guidelines­
870.5000
Acceptable
Dichlorvos
has
been
shown
to
be
a
direct
acting
mutagen
by
common
in
vitro
bacterial
genetic
toxicity
assays
and
in
in
vitro
mammalian
test
systems.
Conflicting
evidence
was
seen
for
clastogenic
activity
in
vivo.

Metabolism­
Rat/
870.7485
41228701
41839901
Acceptable
The
overall
metabolic
profile
suggests
the
involvement
of
the
one­
carbon
pool
biosynthetic
pathway
as
evidenced
by
the
presence
of
a
relatively
large
amount
of
radioactivity
in
the
form
of
expired
14
CO2
and
the
presence
of
dehalogenated
metabolites
as
well
as
urea
and
hippuric
acid.
Page
42
of
151
4.2
FQPA
Hazard
Considerations
4.2.1
Adequacy
of
the
Toxicity
Data
Base
The
toxicology
database
for
dichlorvos
is
complete.
The
FQPA
database
includes
acceptable
developmental
studies
in
rats
and
rabbits,
an
acceptable
2­
generation
rat
reproduction
study,
two
developmental
neurotoxicity
studies,
and
single
dose
gavage
cholinesterase
studies
in
adult
and
preweaning
rats
and
repeat
dose
gavage
studies
in
young
adult
and
preweaning
rats.

4.2.2
Evidence
of
Neurotoxicity
There
is
a
concern
for
neurotoxicity
resulting
from
exposure
to
dichlorvos.
Dichlorvos
is
a
chlorinated
organophosphate
pesticide
cholinesterase
inhibitor,
which
inhibits
plasma,
erythrocyte,
and
brain
cholinesterase.

4.2.3
Developmental
Toxicity
Studies
In
the
rat
study
(
MRID
41951501),
the
maternal
toxicity
LOAEL
was
21
mg/
kg/
day
based
on
clinical
signs
of
toxicity,
reduced
body
weight
gain,
and
food
efficiency;
the
maternal
NOAEL
was
3
mg/
kg/
day.
The
developmental
LOAEL
was
not
established;
the
NOAEL
was
21
mg/
kg/
day.

In
the
rabbit
developmental
study
(
MRID
41802401),
groups
of
NZW
rabbits
(
16/
dose)
received
oral
administration
of
dichlorvos
(
97%)
in
distilled
water
at
dose
levels
of
0,
0.1,
2.5,
or
7.0
mg/
kg/
day
during
gestation
days
7
through
19,
inclusive.
The
maternal
LOAEL
was
2.5
mg/
kg/
day
based
on
maternal
deaths
and
decreased
body
weight
gain;
the
NOAEL
was
0.1
mg/
kg/
day.
No
developmental
toxicity
was
noted;
therefore,
the
NOAEL
for
developmental
toxicity
was
7
mg/
kg/
day.

4.2.4
Reproductive
Toxicity
Study
In
a
two
generation
reproduction
study
in
rats
(
MRID
42483901),
the
parental/
systemic
NOAEL
was
2.3
mg/
kg/
day
and
the
LOAEL
was
8.3
mg/
kg/
day
based
on
a
decreased
incidence
of
estrous
cycling
and
increased
abnormal
cycling
in
F1
females,
reduced
water
intake
in
both
sexes,
and
decreased
plasma,
and
RBC
ChE
activity
at
all
dosage
levels
in
both
sexes
in
both
generations.
In
addition
brain
ChE
was
decreased
in
both
sexes
at
2.3
mg/
kg/
day.
The
NOAEL
for
brain
ChE
was
0.6
mg/
kg/
day
and
the
NOAEL
for
plasma
and
RBC
ChE
depression
was
less
than
0.6
mg/
kg/
day.
The
NOAEL/
LOAEL
for
reproductive/
offspring
toxicity
2.3/
8.3
mg/
kg/
day
based
on
a
decrease
in
the
number
of
dams
bearing
litters,
reduced
fertility
indices,
pregnancy
index,
and
pup
body
weights
on
lactation
Day
4
in
both
F1
matings.
The
offspring
were
not
examined
for
effects
on
cholinesterase.
Page
43
of
151
4.2.5
Pre­
and/
or
Postnatal
Toxicity
There
is
no
concern
for
pre­
and/
or
postnatal
toxicity
resulting
from
exposure
to
dichlorvos.
There
was
no
evidence
for
increased
susceptibility
of
the
rat
and
rabbit
offspring
to
prenatal
or
postnatal
exposure
to
dichlorvos
(
MRID
41951501,
41802401
and
42483901,
respectively)
.
In
both
rat
and
rabbit
developmental
studies,
no
developmental
effects
were
observed.
In
the
reproduction
study,
the
parental/
systemic
NOAEL/
LOAEL
was
2.3/
8.3
mg/
kg/
day
which
was
identical
to
the
reproductive/
offspring
NOAEL/
LOAEL.
In
the
DNT
studies,
at
doses
much
higher
than
used
for
regulation,
increase
in
auditory
startle
reflex
habituation
Vmax
in
PND
23
high
dose
males
was
noted.

4.2.5.1
Determination
of
Susceptibility
The
mode
of
action
for
dichlorvos
is
neurotoxicity
through
the
inhibition
of
cholinesterase
via
phosphorylation
of
the
active
site
of
the
enzyme.
Inhibition
of
cholinesterase
provides
the
most
sensitive
endpoint
for
dichlorvos.
There
are
acute
and
repeated
dosing
studies
which
evaluate
cholinesterase
inhibition
in
juvenile
and
young
adult
rats.
The
Agency
has
completed
a
benchmark
dose
(
BMD)
analysis
of
these
data.
The
Agency's
draft
BMD
technical
guidance
indicates
that
the
BMD
approach
is
a
preferable
alternative
to
the
NOAEL/
LOAEL
approach
(
USEPA,
2000).
The
Office
of
Pesticide
Programs
is
increasing
its
use
of
BMD
techniques
in
its
hazard
assessments
and
risk
characterizations
for
use
in
developing
points
of
departure
and
in
considering
relative
sensitivity
of
adult
and
juvenile
animals.
BMDs
are
preferred
over
the
NOAEL/
LOAEL
as
NOAELs/
LOAELs
are
highly
dependent
on
dose
selection
in
that
they
are
limited
to
the
doses
included
in
a
study.
BMD
analysis
also
considers
the
entire
dose
response
curve
and
not
just
a
single
point.
Moreover,
the
NOAEL/
LOAEL
approach
does
not
account
for
the
uncertainty
in
the
estimate
of
the
dose­
response.
The
dichlorvos
BMD
analysis
was
developed
using
the
exponential
model
provided
in
EPA's
OPCum
Risk
software.
The
application
of
the
exponential
model
to
cholinesterase
data
from
OPs
and
N­
methyl
carbamate
pesticides
has
been
reviewed
by
the
FIFRA
Scientific
Advisory
Board
on
multiple
occasions.
This
model
and
the
supporting
computer
code
are
publicly
available
for
download,
review,
and
use
at
www.
epa.
gov/
pesticides/
cumulative/
EPA_
approach_
methods.
htm.

The
Agency
calculated
the
estimated
dose
to
result
in
10%
inhibition
(
BMD10)
and
the
lower
95%
confidence
limit
on
the
BMD10
(
BMDL10).
Brain
and
RBC
ChE
data
from
acute
dosing
to
post­
natal
day
8
(
PND8)
and
young
adult
rats
were
extracted
from
MRID
nos.
45805703
and
45842301.
The
acute
BMDs10
range
from
approximately
1.3
mg/
kg
to
2.0
mg/
kg
for
each
compartment,
sex
and
age
group.
Regarding
repeated
exposures,
brain
and
RBC
ChE
data
from
the
repeated
dosing
studies
in
juvenile
and
young
adult
rat
were
extracted
from
MRID
nos.
46433201
and
46153304.
As
described
in
detail
in
the
Data
Evaluation
Record
(
DER)
for
these
studies,
the
ChE
activity
measurements
in
some
control
groups
are
unusually
high
for
the
laboratory
which
conducted
the
repeated
exposure
study.
The
registrant,
AMVAC,
provided
historical
control
values
for
brain
and
RBC
ChE
activity.
BMD
estimates
were
developed
using
both
the
concurrent
and
pooled
historical
control
values.
It
is
preferred
to
evaluate
relative
sensitivity
using
concurrent
Page
44
of
151
controls
however
in
this
case
use
of
the
historical
control
values
provides
helpful
characterization.
Overall,
for
the
repeated
exposure,
the
BMDs
ranged
from
approximately
0.5
mg/
kg
to
1.2
mg/
kg
when
using
the
historical
or
concurrent
controls
and
are
thus
similar
between
compartments,
sexes
and
age
groups.

4.2.5.2
Degree
of
Concern
Analysis
and
Residual
Uncertainties
for
Pre
and/
or
Post­
natal
Susceptibility
Based
on
the
BMD
analysis
summarized
above,
the
dichlorvos
risk
assessment
team
has
determined
that
the
FQPA
Safety
Factor
can
be
reduced
to
1X
for
acute
and
repeated
exposures
of
dichlorvos.
The
BMD
estimates
are
similar
for
juvenile
and
adult
rats,
and
thus
indicates
no
sensitivity
to
young
animals
(
Lowit,
A.,
2006).

4.2.6.
Traditional
Safety
Factors
Any
traditional
safety
factors
other
than
that
standard
uncertainty
factors,
the
interspecies
extrapolation
factor,
and
the
intraspecies
variability
factor,
are
considered
to
be
FQPA
safety
factors.
For
dichlorvos,
a
LOAEL
from
a
human
21­
day
oral
study
is
used
as
an
endpoint
for
short
term
residential
exposure
scenarios.
The
LOAEL
to
NOAEL
factor
of
3x
is
considered
to
be
an
FQPA
Safety
Factor.

4.3
Hazard
Identification
and
Toxicity
Endpoint
Selection
4.3.1.
Acute
Reference
Dose
(
aRfD)
­
General
Population
Study
Selected:
Acute
Cholinesterase
Study
in
Rats
Non­
guideline
MRID:
45805703
Title:
Dichlorvos:
Third
Acute
cholinesterase
inhibition
study
in
rats;
Twomey,
K.
June
26,
2002.

Executive
Summary:
In
the
third
acute
oral
cholinesterase
toxicity
study
in
rats
(
MRID
45805703),
groups
of
15
male
and
15
female
Wistar­
derived
rats
were
administered
single
oral
doses
of
dichlorvos
(
purity
of
99.0%)
at
dose
levels
of
0
(
control),
1
mg/
kg,
or
5
mg
dichlorvos/
kg
on
Day
1
of
the
study.
Nine
males
were
dosed
with
35
mg
dichlorvos/
kg,
but
due
to
the
severe
cholinergic
signs,
no
further
dosing
at
this
level
was
conducted.
Two
additional
groups
of
15
females
were
dosed
with
0
or
15
mg
dichlorvos/
kg
as
a
single
oral
dose.
All
animals
were
observed
prior
to
the
start
of
the
study
and
on
Day
1
at
time
of
expected
peak
effect
(
30
minutes
post
dose)
for
any
changes
in
clinical
condition.
Body
weights
were
measured
at
Day
1,
Page
45
of
151
8,
and
15.
At
scheduled
termination
at
1
hour
post
dosing,
5/
sex/
dose
animals
were
sacrificed
and
brains
were
removed
and
weighed.
Cardiac
blood
samples
were
taken
post
mortem
for
determination
of
erythrocyte
cholinesterase
activity.
The
cerebellum,
cerebral
cortex,
hippocampus,
half
and
remainder
of
the
brain
were
dissected
out
and
sent
for
determination
of
cholinesterase
activity.
Dose
analysis
measurements
were
acceptable.
On
day
1
of
dosing,
severe
toxicity
in
9
males
of
the
high­
dose
group
(
35
mg/
kg)
was
observed.
Four
of
these
males
were
killed
for
humane
reasons
within
1
hour
of
dosing.
Those
sacrificed
and
the
remaining
animals
in
this
group
displayed
some
or
all
of
the
following
signs:
decreased
activity,
irregular
breathing,
clonic
convulsions,
fasiculations,
prostration,
decreased
righting
and
splay
reflexes,
and
salivation.
One
female
dosed
with
15
mg/
kg
had
miosis
and
fasiculations.
There
were
no
meaningful
(
i.
e.,
miosis)
treatment
related
clinical
signs
in
animals
of
the
1
or
5
mg/
kg
dose
groups.
Body
and
brain
weight
comparisons
between
treated
groups
of
both
sexes
and
their
respective
controls
were
not
statistically
significantly
affected.
Statistically
significant
cholinesterase
depression
occurred
at
the
following
doses
in
blood
or
brain
segments
for
each
sex:
cerebellum
(
males,
35
mg/
kg;
females,
5
and
15
mg/
kg),
cortex
(
males,
5
and
35
mg/
kg;
females,
5
and
15
mg/
kg),
hippocampus
(
males,
35
mg/
kg;
females,
5
and
15
mg/
kg),
remainder
(
males
35
mg/
kg;
females
5
and
15
mg/
kg),
half­
brain
(
males,
35
mg/
kg;
females,
5
and
15
mg/
kg),
erythrocyte
(
males,
5
and
35
mg/
kg;
females,
5
and
15
mg/
kg).
There
was
no
meaningful
cholinesterase
depression
at
1
mg/
kg
on
erythrocyte
or
brain
segments
for
both
sexes
killed
at
1
hour
post­
dosing
on
day
1
or
on
day
8
or
day
15
in
comparison
to
controls.
Due
to
a
lack
of
cholinesterase
inhibition
in
some
animals
on
day
1,
the
animals
scheduled
for
cholinesterase
measurement
on
day
8
and
15
were
sacrificed.

The
LOAEL
for
erythrocyte
and
brain
cholinesterase
inhibition
is
5
mg/
kg
in
both
sexes.
The
NOAEL
for
erythrocyte
and
brain
cholinesterase
inhibition
is
1
mg/
kg
in
both
sexes.

This
acute
oral
cholinesterase
toxicity
study
is
classified
acceptable/
non­
guideline.
This
study
does
satisfy
the
requirement
(
modified
OPPTS
870.1100;
OECD
401)
for
an
acute
oral
cholinesterase
toxicity
study
on
the
technical.

Dose
and
endpoint
for
establishing
the
aRfD:
A
Benchmark
Dose
Analysis
(
BMD)
was
conducted
for
the
dichlorvos
cholinesterase
inhibition
data
by
RRB4
(
Daiss
B.,
2004).
The
Agency's
BMDS
program
(
Benchmark
Dose
Software
version
1.3.2)
was
used
to
derive
the
BMDL10,
the
estimated
dose
that
results
in
10%
inhibition
of
cholinesterase,
and
the
BMDL10,
the
lower
95%
confidence
interval
on
the
BMDL10,
for
the
RBC
cholinesterase
data.
For
this
analysis,
the
polynomial
continuous
model
default
option
of
relative
deviation
was
used
for
the
benchmark
response
(
BMR)
type,
with
a
corresponding
BMR
factor
of
0.1
used
as
a
basis
for
BMD
and
BMDL10
derivation.

The
BMDL10
of
0.8
mg/
kg
based
on
Day
1
female
brain
ChE
depression
was
selected
as
the
lowest
value
of
all
the
studies
available
which
were
analyzed
by
BMD.
Page
46
of
151
A
second
BMD
analysis
was
done
for
dichlorvos
to
be
used
in
the
OP
cumulative
analysis.
This
BMD
analysis
was
done
using
the
OPCumRisk
software.
Similar
results
were
obtained.
The
decision
algorithm
and
technical
details
of
the
"
basic"
exponential
model
used
in
this
BMD
analysis
can
be
obtained
at
www.
epa.
gov/
scipoly/
sap/
2001/
september/
rpfappendix1.
pdf
Uncertainty
factor:
100
(
10x
for
interspecies
differences
and
10x
for
intraspecies
variation).

FQPA
Safety
Factor:
The
FQPA
Safety
Factor
has
been
reduced
to
1x,
since
BMD
analysis
of
studies
with
pup
and
adult
ChE
depression
results
did
not
demonstrate
any
substantial
numerical
differences
in
BMDL
values
(
all
values
were
approximately
1
mg/
kg)
for
either
RBC
or
brain
cholinesterase.

Comments
about
Study/
Endpoint/
Uncertainty
Factor:
There
are
no
specific
issues
of
concern
in
the
assessment
of
the
rat
acute
cholinesterase
studies.

4.3.2.
Chronic
Reference
Dose
(
cPAD)

Study
Selected:
Chronic
Toxicity­
Dog
870.4100
(
formerly
§
83­
1b)

MRID
No.
41593101
Executive
Summary:
In
a
chronic
feeding
study,
groups
of
beagle
dogs
were
administered
dichlorvos
by
capsule
for
52
weeks
at
dose
levels
of
0,
0.1,
1.0
and
3.0
mg/
kg/
day.
The
0.1
mg/
kg/
day
dose
was
lowered
to
0.05
mg/
kg/
day
on
day
22
due
to
the
inhibition
of
plasma
cholinesterase
noted
after
12
days
(
plasma
cholinesterase
was
decreased
in
males
(
21.1%)
and
females
(
25.7%)
at
week
2
in
the
0.1
mg/
kg/
day
group).
At
time
points
after
week
2,
plasma
cholinesterase
activity
was
only
significantly
reduced
in
males
(
39.1
to
59.2%)
and
females
(
41.0
to
56.7%)
in
the
mid­
dose
group
and
in
males
(
65.1
to
74.3%)
and
females
(
61.1
to
74.2%)
in
the
high
dose
group.
Although
RBC
cholinesterase
activity
was
reduced
in
males
(
23.6%)
and
females
(
50.1%)
at
week
6
in
the
low­
dose
group,
this
was
believed
to
be
an
effect
on
RBC
cholinesterase
of
the
higher
dose
of
0.1
mg/
kg/
day.
Much
lower
levels
of
inhibition
were
observed
in
this
group
after
week
6.
At
time
points
after
week
6,
RBC
cholinesterase
activity
was
only
significantly
decreased
in
males
(
43.0
to
53.9)
and
females
(
38.0
to
51.9)
in
the
middose
group
and
in
males
(
81.2
to
86.9%)
and
females
79.2
to
82.5%)
in
the
high­
dose
groups.
Brain
cholinesterase
activity
was
significantly
reduced
in
males
(
22%)
in
the
mid­
dose
group
and
in
males
(
47%)
and
females
(
29%)
in
the
high
dose
group.
The
NOAEL
was
0.05
mg/
kg/
day
and
Acute
PAD
(
General
population)
=
0.8
mg/
kg
=
0.008
mg/
kg
100
Page
47
of
151
the
LOAEL
was
0.1
mg/
kg/
day
based
on
plasma
and
RBC
cholinesterase
inhibition
in
males
and
females.

Dose
and
Endpoint
for
Establishing
cRfD:
NOAEL
=
0.05
mg/
kg
based
on
plasma
and
RBC
cholinesterase
inhibition
in
males
and
females
at
0.1
mg/
kg/
day
(
LOAEL).

Uncertainty
Factor:
100x
(
10x
for
interspecies
variation,
10x
for
intraspecies
extrapolation)

FQPA
Safety
Factor:
1x.

Comments
about
Study/
Endpoint/
Uncertainty
Factor:
The
human
data
(
discussed
in
the
next
section)
were
not
used
since
RBC
cholinesterase
inhibition
did
not
demonstrate
a
steady
state
(
equilibrium)
by
the
end
of
the
study
at
three
weeks,
i.
e.
the
inhibition
of
cholinesterase
was
progressive
and
a
NOAEL
was
not
achieved.
This
conclusion
was
supported
by
the
HSRB.

4.3.3.
Incidental
Oral
Exposure
(
Short
Term)

Incidental
Oral
Exposure:
Short­
Term
(
1­
30
days)

Study
Selected:
Subchronic
oral
toxicity
study
in
human
subjects
§
Non­
guideline
MRID
No.:
44248801
Executive
Summary:
In
a
single
blind
oral
study
6
fasted
male
volunteers
were
administered
7
mg
of
dichlorvos
in
corn
oil
(
equivalent
to
approximately
0.1
mg/
kg/
d)
via
capsule
daily
for
21
days.
Three
control
subjects
received
corn
oil
as
a
placebo.
Baseline
values
for
RBC
cholinesterase
activity
for
each
study
participant
were
determined.
After
dosing
started,
RBC
cholinesterase
activity
was
monitored
on
days
2,
4,
7,
9,
11,
14,
16,
and
18,
then
on
day
25
or
28
post
dosing.
No
clinical
signs
attributable
to
administration
of
dichlorvos
was
reported.
Mean
RBC
cholinesterase
activity
was
statistically
significantly
reduced
in
treated
subjects
on
days
7,
11,
14,
16,
and
18.
These
values
were
8,
10,
14,
14,
and
16
percent
below
the
pre­
dose
mean.
Under
the
study
conditions,
a
LOAEL
for
RBC
cholinesterase
inhibition
was
established
at
0.1
mg/
kg/
d.
A
NOAEL
was
not
established.

Dose
and
Endpoint
for
Risk
Assessment:
The
LOAEL
of
0.1
mg/
kg/
d
based
on
statistically
significant
decreases
in
RBC
cholinesterase
inhibition.
Chronic
PAD
=
0.05
mg/
kg/
day
=
0.0005
mg/
kg/
day
100
Page
48
of
151
Comments
about
Study/
Endpoint:
The
human
study
was
selected
because
it
is
a
subchronic
study
of
appropriate
duration
and
is
the
lowest
LOAEL
established
for
RBC
cholinesterase
inhibition
in
a
repeated
oral
exposure
to
dichlorvos.
Uncertainty
factors
account
for
intraspecies
variability
(
10x).
Since
the
study
was
conducted
in
human
subjects,
there
was
no
need
to
account
for
interspecies
extrapolation.

FQPA
Safety
Factor:
3x
A
3x
for
lack
of
a
NOAEL
is
considered
an
FQPA
safety
factor.

Target
MOE:
30
4.3.4.
Dermal
Absorption
Dermal
Absorption
Factor:
The
dermal
absorption
rate
for
dichlorvos
was
estimated
to
be
approximately
11%
in
10
hours
of
exposure
based
on
an
acceptable
dermal
absorption
study
in
rats
(
MRID
41435201).

4.3.5.
Dermal
Exposure
(
Acute)

Study
Selected:
Acute
Cholinesterase
Study
in
Rats
Non­
guideline
MRID:
45805703
(
see
discussion
under
Section
4.3.1
Acute
Reference
Dose)

Target
MOE:
100
4.3.6.
Dermal
Exposure
(
Short­,
Intermediate­,
and
Long­
Term)

Study
Selected:
Subchronic
oral
toxicity
study
in
human
subjects
§
Non­
guideline
MRID
No.:
44248801
Executive
Summary:
(
See
discussion
above)

Dose
and
Endpoint
for
Risk
Assessment:
The
LOAEL
of
0.1
mg/
kg/
d
based
on
statistically
significant
decreases
in
RBC
cholinesterase
inhibition.

Comments
about
Study/
Endpoint:
The
human
study
was
selected
because
it
is
a
subchronic
study
of
appropriate
duration
and
is
the
lowest
LOAEL
established
for
RBC
cholinesterase
inhibition
in
a
repeated
oral
exposure
to
dichlorvos.
Since
the
study
was
conducted
in
human
subjects,
there
was
no
need
to
account
for
the
interspecies
extrapolation.
Uncertainty
factors
account
for
intraspecies
variability
(
10x).

FQPA
Safety
Factor:
3x
A
3x
for
lack
of
a
NOAEL
is
considered
an
FQPA
safety
factor.

Target
MOE:
30
Page
49
of
151
4.3.7.
Inhalation
Exposure
(
Acute)

Study
Selected:
Acute
Cholinesterase
Study
in
Rats
Non­
guideline
MRID:
45805703
(
see
discussion
under
Section
4.3.1
Acute
Reference
Dose)

Target
MOE:
100,
or
30
if
RfC
methodology
is
used.
If
RfC
methodology
is
used,
the
interspecies
extrapolation
factor
is
reduced
from
10x
to
3x.

4.3.8.
Inhalation
Exposure
(
Short
and
Intermediate
Term)

Study
Selected:
Subchronic
oral
toxicity
study
in
human
subjects
§
Non­
guideline
MRID
No.:
44248801
(
See
discussion
above
under
dermal
exposure)

Comments
about
Study/
Endpoint:
The
uncertainty
factors
are
the
same
as
discussed
above
under
Dermal
Exposure.

4.3.9.
Inhalation
Exposure
(
Long
Term)

Study
Selected:
2­
year
Rat
Inhalation/
carcinogenicity
870.4200a
(
formerly
§
83­
2a)

MRID
No.
0057695,
00632569
Executive
Summary:
The
critical
study
for
inhalation
risk
assessment
for
Dichlorvos
is
an
inhalation
carcinogenicity
study
in
rats.
Groups
of
50/
sex/
group
Carworth
rats
were
exposed
to
atmospheres
containing
Dichlorvos
vapor
for
23
hours/
day,
7
days/
week
at
concentrations
of
0,
0.05,
0.5,
and
5
mg/
m3
equivalent
to
0.055,
0.5,
and
5.0
mg/
kg/
day
for
2
years.
Animals
were
observed
for
clinical
signs
of
toxicity,
hematology,
and
clinical
chemistry.
Plasma,
RBC
and
brain
cholinesterase
activity
were
determined
at
study
termination.
There
were
no
toxic
signs,
and
no
organ
weight
or
organ
to
body
weight
changes,
or
hematological
changes
attributable
to
administration
of
Dichlorvos.
Body
weights
were
significantly
decreased
in
mid
and
high
dose
males
up
to
study
termination,
and
in
high
dose
females
throughout
the
study.
Plasma,
RBC,
and
brain
cholinesterase
activity
were
significantly
reduced
in
the
mid
and
high
dose
groups
(
76,
72,
and
90
and
83,
68,
and
90
percent
of
control
in
mid
dose
males
and
females,
and
to
38,
4,
and
21,
and
22,
5,
and
16
percent
of
control
in
the
high
dose
male
and
female
groups,
respectively).
RBC
cholinesterase
activity
was
reduced
to
88
percent
of
control
in
the
low
dose
females.
The
BMD10
for
RBC
cholinesterase
inhibition
in
female
rats
was
0.15
mg/
m3
and
the
BMDL10
was
0.07
mg/
m3.

Comments
about
Study/
Endpoint:
This
is
the
same
inhalation
study
which
has
been
used
by
the
Agency
RfD/
RfC
Work
Group
in
deriving
the
Reference
Concentration
(
RfC)
for
Dichlorvos.
An
Agency
RfC
document
is
available
on
IRIS.
Page
50
of
151
The
BMDL10
of
0.07
mg/
m3
(
or
0.00007
mg/
L)
was
selected
for
chronic
inhalation
risk
assessment
scenarios.
Uncertainty
factors
account
for
intraspecies
variation
(
10x)
and
3x
for
interspecies
variation.
(
The
interspecies
extrapolation
factor
is
reduced
to
3x
when
the
endpoint
is
expressed
in
concentration
units
(
RfC
methodology)).

FQPA
Safety
Factor:
1x
Target
MOE:
30
4.3.10.
Margins
of
Exposure
A
summary
of
target
Levels
of
Concern
for
dichlorvos
risk
assessment
is
provided
in
Table
4.3.10.

Table
4.3.10.
Target
Levels
of
Concern
(
i.
e.,
Margins
of
Exposure)
for
Dichlorvos
Exposure
Scenarios
Route
Acute
(<
1
Day)
Short­
Term
(
1­
30
Days)
Intermediate­
Term
(
1
­
6
Months)
Long­
Term
(>
6
Months)

Occupational
(
Worker)
Exposure
Dermal
100
30
30
N/
A
Inhalation
100/
30*
30
30
N/
A
Residential
(
Non­
Dietary)
Exposure
Oral
100
30
N/
A
N/
A
Dermal
100
30
30
30
Inhalation
100/
30*
N/
A
N/
A
30
*
The
higher
target
MOE
is
used
when
the
endpoint
is
expressed
in
mg/
kg/
day
(
for
exposure
during
application).
The
lower
target
MOE
is
used
when
the
endpoint
is
expressed
in
concentration
units
(
RfC
methodology,
used
for
post­
application
risk
assessment).
There
is
no
long
term
residential
inhalation
exposure
during
application.

For
short­
and
intermediate­
term
oral
and
dermal
exposures,
the
uncertainty
factor
is
based
on
the
conventional
uncertainty
factor
of
10X
for
intraspecies
variability.
No
factor
is
needed
for
interspecies
extrapolation
because
the
endpoint
is
based
on
a
human
study.
A
3x
factor
for
lack
of
a
NOAEL
is
considered
an
FQPA
safety
factor.

For
short­
and
intermediate­
term
inhalation
exposure,
the
uncertainty
factor
is
based
on
the
conventional
uncertainty
factor
of
10x
for
intraspecies
extrapolation,
3x
for
the
use
of
a
LOAEL.
For
long
term
inhalation
exposure,
the
uncertainty
factor
is
based
on
the
conventional
uncertainty
factor
of
10x
for
intraspecies
extrapolation,
3x
for
interspecies
extrapolation
(
based
on
air
concentrations),
The
FQPA
safety
factor
is
reduced
to
1x
for
residential
exposure
assessments.

For
acute
inhalation
exposure,
the
uncertainty
factor
is
based
on
the
conventional
uncertainty
factor
of
100x
(
10X
for
interspecies
extrapolation
and
10x
for
intraspecies
variability),
when
the
Page
51
of
151
endpoint
is
expressed
in
mg/
kg/
day.
When
the
endpoint
is
expressed
in
concentration
units,
the
interspecies
extrapolation
factor
is
reduced
to
3x.
The
FQPA
Safety
Factor
has
been
reduced
to
1x.
The
target
MOE
is
30.

4.3.11.
Recommendation
for
Aggregate
Exposure
Risk
Assessments
Under
FQPA,
when
there
are
potential
residential
exposures
to
the
pesticide,
aggregate
risk
assessment
must
consider
exposures
from
residues
in
food
commodities
and
drinking
water,
as
well
as
exposures
arising
from
non­
dietary
sources
(
e.
g.,
incidental
oral,
dermal
and
inhalation
exposures)
from
the
residential
scenarios.
Since
there
are
residential
uses
of
dichlorvos
and
the
effect
is
cholinesterase
inhibition
for
all
endpoints,
aggregation
of
risk
from
non
dietary
sources
is
required.
Since
the
target
MOEs
differ,
aggregation
of
risk
will
be
assessed
using
the
aggregate
risk
index
(
ARI).
The
target
ARI
is
1.

4.3.12.
Classification
of
Carcinogenic
Potential
Dichlorvos
has
been
classified
as
a
category
C
carcinogen
based
primarily
on
increased
incidences
of
forestomach
tumors
in
female
mice
and
mononuclear
cell
leukemia
(
MCL)
in
male
Fischer
344
rats.
Both
tumor
types
have
been
used
at
various
times
to
derive
q1*
s
for
quantitation
of
cancer
risk.
After
lengthy
deliberations
and
consultations
with
EPA's
Scientific
Advisory
Panel
(
SAP)
and
cancer
experts
with
the
National
Toxicology
Program,
HED's
Cancer
Assessment
Review
Committee
has
classified
dichlorvos
as
"
suggestive"
and
not
requiring
quantitation
of
cancer
risks
based
on
the
following
rationale:

1)
MCL
in
the
male
Fischer
rat
has
certain
properties
in
terms
of
variability
and
reliability
which
limit
its
usefulness
for
human
risk
assessment.

2)
The
forestomach
tumors
in
mice
observed
at
gavage
doses
causing
inhibition
of
plasma
and
red
blood
cell
cholinesterase
and
cholinergic
signs,
are
also
limited
in
their
use
for
human
risk
assessment.

3)
The
fact
that
dichlorvos
is
only
positive
by
the
gavage
route
and
negative
by
the
inhalation
route,
which
is
the
major
route
of
human
exposure,
indicates
that
any
classification
by
the
oral
route
may
be
limited
since
localized
effects
in
the
forestomach
may
not
be
applicable
to
human
risk
assessment.
Page
52
of
151
4.4
Summary
of
Toxicology
Endpoint
Selection
for
Dichlorvos
Table
4.4.
Summary
of
Toxicological
Doses
and
Endpoints
for
Dichlorvos
for
Use
in
Dietary
and
Non­
Occupational
Human
Health
Risk
Assessments
Exposure
Scenario
Point
of
Departure
Uncertainty/
FQPA
Safety
Factors
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
Acute
Dietary
(
General
population
including
infants
and
children)
BMDL10
=
0.8
mg/
kg/
day
UFA
=
10x
UFH
=
10x
FQPA
SF
=
1x
Acute
RfD
=
0.008
mg/
kg/
day
aPAD
=
0.008
mg/
kg/
day
Rat
acute
oral
cholinesterase
studies
­
RBC
and
Brain
ChE
depression.
NOAEL
=
1
mg/
kg/
day,
LOAEL
=
5
mg/
kg/
day,
BMD
=
1.6
mg/
kg/
day
for
brain
ChE
depression
(
F)

Chronic
Dietary
(
All
populations)
NOAEL=
0.05
mg/
kg/
day
UFA
=
10x
UFH
=
10x
FQPA
SF
=
1x
Chronic
RfD
=
0.0005
mg/
kg/
day
cPAD
=
0.0005
mg/
kg/
day
1­
Year
Dog
study
LOAEL
=
0.1
mg/
kg/
day
based
on
Plasma
and
RBC
ChE
depression
Short­
Term
Incidental
Oral
(
1­
30
days)
LOAEL=
0.1
mg/
kg/
day
UFH=
10x
FQPA
SF
=
3x
(
UFL)
Residential
LOC
MOE
=
30
Human
21­
day
oral
study
LOAEL
=
0.1
mg/
kg/
day
based
on
RBC
ChE
depression
Acute
Dermal
and
Acute
Incidental
Oral
BMDL10
=
0.8
mg/
kg/
day
dermal
absorption=
11%
UFA
=
10x
UFH
=
10x
FQPA
SF
=
1x
Residential
LOC
MOE
=
100
Rat
acute
oral
cholinesterase
studies
­
RBC
and
Brain
ChE
depression.
NOAEL
=
1
mg/
kg/
day,
LOAEL
=
5
mg/
kg/
day,
BMD
=
1.6
mg/
kg/
day
for
brain
ChE
depression
(
F)

Short­,
Intermediateand
Long­
Term
Dermal
Oral
study
LOAEL=
0.1
mg/
kg/
day
dermal
absorption=
11%
UFH
=
10x
FQPA
SF
=
3x
(
UFL)
Residential
LOC
MOE
=
30
Human
21­
day
oral
study
LOAEL
=
0.1
mg/
kg/
day
based
on
RBC
ChE
depression
Acute
Inhalation
(
1
day)
Oral
study
BMDL10
=
0.8
mg/
kg/
day
(
inhalation
absorption
rate
=
100%)
Air
concentration
Equivalent
=
0.8
mg/
m
3
*
UFA
=
10x
UFH
=
10x
or
3x**
FQPA
SF
=
1x
Residential
LOC
MOE
=
100/
30**
Rat
acute
oral
cholinesterase
studies
­
RBC
and
Brain
ChE
depression.
NOAEL
=
1
mg/
kg/
day,
LOAEL
=
5
mg/
kg/
day,
BMD
=
1.6
mg/
kg/
day
for
brain
ChE
depression
(
F)

Short­
and
Intermediate­
term
Inhalation
of
vapors
Oral
study
LOAEL=
0.1
mg/
kg/
day
UF=
30
Concentration
equivalent=
0.35
mg/
m
3
*
UFH
=
10x
FQPA
SF
=
3x
(
UFL)
Residential
LOC
MOE
=
30
Human
21­
day
oral
study
LOAEL
=
0.1
mg/
kg/
day
based
on
RBC
ChE
depression
Short­
and
Intermediate­
Term
Inhalation
during
application
LOAEL=
0.1
mg/
kg/
day
UFH
=
10x
FQPA
SF
=
3x
(
UFL)
Residential
LOC
MOE
=
30
Human
21­
day
oral
study
LOAEL
=
0.1
mg/
kg/
day
based
on
RBC
ChE
depression
Long­
Term
Inhalation
of
vapors
BMDL10
=
0.07
mg/
m
3
UFA
=
10x
UFH
=
3x**
FQPA
SF
=
1x
Residential
LOC
=
30
2­
year
Rat
Inhalation
BMD
=
0.15
mg/
m
3
based
on
RBC
ChE
depression
(
F)

Cancer
(
oral,
dermal,
inhalation)
"
suggestive"
evidence
of
carcinogenicity
not
quantifiable
under
the
1999
Draft
Agency
Cancer
Guidelines
Page
53
of
151
Point
of
Departure
(
POD)
=
A
data
point
or
an
estimated
point
that
is
derived
from
observed
dose­
response
data
and
used
to
mark
the
beginning
of
extrapolation
to
determine
risk
associated
with
lower
environmentally
relevant
human
exposures.
NOAEL
=
no
observed
adverse
effect
level.
LOAEL
=
lowest
observed
adverse
effect
level.
UF
=
uncertainty
factor.
UFA
=
extrapolation
from
animal
to
human
(
intraspecies).
UFH
=
potential
variation
in
sensitivity
among
members
of
the
human
population
(
interspecies).
UFL
=
use
of
a
LOAEL
to
extrapolate
a
NOAEL.
UFS
=
use
of
a
short­
term
study
for
long­
term
risk
assessment.
UFDB
=
to
account
for
the
absence
of
key
date
(
i.
e.,
lack
of
a
critical
study).
FQPA
SF
=
FQPA
Safety
Factor.
PAD
=
population
adjusted
dose
(
a
=
acute,
c
=
chronic).
RfD
=
reference
dose.
MOE
=
margin
of
exposure.
LOC
=
level
of
concern.
N/
A
=
Not
Applicable
*
Calculation
of
concentration
equivalent
BMDL10
and
LOAEL
Acute
Inhalation
BMDL10
0.8
mg/
kg/
day
x
0.35
kg
/
0.34
m
3
/
day
=
0.8
mg/
m
3
Short­
and
Intermediate­
term
inhalation
of
vapors
LOAEL
0.1
mg/
kg/
day
x
70
kg
/
20
m
3
/
day
=
0.35
mg/
m
3
**
Since
the
NOAEL
is
expressed
in
concentration
units
(
RfC
methodology),
the
interspecies
extrapolation
factor
is
3x
(
for
the
acute
and
long
term
inhalation
scenarios),
for
a
total
UF
of
30
for
acute
inhalation
and
long
term
inhalation.
The
residential
target
MOE
is
30
for
acute
inhalation,
since
the
FQPA
safety
factor
has
been
reduced
to
1.
The
Residential
target
MOE
is
30
for
long
term
inhalation,
since
the
FQPA
safety
factor
is
1.

4.4
FQPA
Safety
factor
The
HED
dichlorvos
team
evaluated
the
hazard
and
exposure
data
to
determine
if
the
FQPA10x
safety
factor
should
be
retained,
reduced
or
removed
focusing
primarily
on
the
following
points:

 
The
standard
developmental
and
reproductive
toxicity
studies
and
the
developmental
neurotoxicity
study
submitted
to
the
Agency
showed
no
residual
concern
for
sensitivity
or
susceptibility
of
rats,
or
rabbits
to
in
utero
and/
or
postnatal
exposure
to
dichlorvos;

 
In
repeated
dose
studies
with
dichlorvos
in
rats,
young
rats
were
less
sensitive
than
adult
rats
with
respect
to
inhibition
of
RBC
cholinesterase;
in
repeated
dose
studies
with
dichlorvos
in
rats,
based
on
the
BMD
analysis,
there
was
no
difference
between
young
rats
and
adult
rats
with
respect
to
inhibition
of
brain
cholinesterase;
in
repeated
dose
studies,
the
BMDs
are
similar
between
compartments,
sexes
and
age
groups.

 
Some
exposure
scenarios
are
based
on
a
LOAEL.

 
The
dietary
food
exposure
assessment
utilizes
a
combination
of
monitoring
data,
field
trial
data,
and
tolerance
level
residues.
Percent
crop
treated
information
is
used
where
available.
These
data
will
not
underestimate
chronic
exposures/
risks.

 
The
dietary
drinking
water
assessment
(
Tier
2
estimates)
utilizes
values
generated
by
model
and
associated
modeling
parameters
which
are
designed
to
provide
conservative,
health
protective,
high­
end
estimates
of
water
concentrations.

 
The
residential
exposure
assessment
utilizes
dichlorvos
specific
monitoring
data,
activity
specific
transfer
coefficients
and
chemical­
specific
turf
transferable
residue
(
TTR)
studies
for
the
postapplication
turf
scenario
(
use
of
trichlorfon).
The
refined
residential
assessment
is
based
on
reliable
data
and
is
unlikely
to
underestimate
exposure/
risk.
Page
54
of
151
The
dichlorvos
team
concluded
that
the
FQPA
Safety
Factor
can
be
reduced
to
1x,
except
for
short
term
oral
and
dermal
scenarios,
for
which
the
FQPA
factor
is
retained
at
3x
to
account
for
the
lack
of
a
NOAEL.

4.5.
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
dichlorvos,
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,
dichlorvos
may
be
subjected
to
further
screening
and/
or
testing
to
better
characterize
effects
related
to
endocrine
disruption.
Page
55
of
151
5.0
Public
Health
Data
The
Agency
has
conducted
a
review
of
reported
poisoning
incidents
associated
with
human
exposure
to
dichlorvos.
The
Agency
has
consulted
the
following
data
bases
for
the
poisoning
incident
data
on
the
active
ingredient
dichlorvos:
(
1)
the
OPP
Incident
Data
System,
which
contains
anecdotal
reports
of
incidents
from
various
sources,
including
registrants,
other
federal
and
state
health
and
environmental
agencies
and
individual
consumers,
submitted
to
OPP
since
1992,
(
2)
Poison
Control
Center
Data
for
28
organophosphate
and
carbamate
chemicals
for
the
years
1985
through
1992,
(
3)
California
Department
of
Food
and
Agriculture
reports
(
superceded
by
the
Department
of
Pesticide
Regulation),
which
contain
uniform
data
on
suspected
pesticide
poisonings
collected
since
1982,
and
(
4)
National
Pesticide
Telecommunications
Network
(
NPTN),
which
is
a
toll­
free
information
service
supported
by
OPP.
In
addition,
the
Agency
has
received
public
comments
regarding
poisoning
incidences
associated
with
dichlorvos
as
comments
to
the
Proposed
Notice
of
Intent
to
Cancel
(
PD
2/
3)
and
in
Phase
3
of
the
RED
process.
Specific
comments
on
incidences
were
received
from
Amvac
Chemical
Corporation,
the
Japanese
Resin
Strip
Manufacturer's
association,
and
two
private
citizens,
Arturo
Haran
and
Eric
Levine.

Exposure
to
dichlorvos
has
resulted
in
poisoning
incidents.
Dichlorvos
has
widespread
use
patterns
in
the
home
and
agricultural
environments.
Many
of
these
uses
(
e.
g.,
poultry
houses)
are
atypical
of
most
organophosphates,
which
make
it
difficult
to
compare
the
risk.
According
to
California
data,
it
appears
that
a
majority
of
cases
involved
illnesses
to
workers
indoors
that
entered
a
facility
previously
fumigated
with
dichlorvos.
Often
exposure
results
from
inadequate
ventilation
before
persons
are
allowed
in
or
near
the
treated
area
or
lack
of
proper
personal
protective
equipment
(
PPE).

Dichlorvos
can
cause
systemic
illness,
including
respiratory
effects,
to
individuals
who
are
exposed
after
fumigation.

5.1
Incident
Reports
Incidents
with
dichlorvos
are
discussed
in
a
separate
review.
Blondell,
J
and
Spann,
M.
1998.
More
recent
information
is
available.
However,
the
more
recent
information
is
very
similar
to
that
reported
in
1998,
and
doesn't
change
our
conclusions
(
J.
Blondell,
personal
communication
with
S.
Hummel,
1/
4/
2005).

5.2
Other
The
Agency
received
additional
information
on
poisoning
incidents
associated
with
dichlorvos
as
comments
to
the
PD
2/
3
and
to
Phase
3
of
the
RED.
Specific
comments
on
incidents
were
received
from
Amvac
Chemical
Corporation,
the
Japanese
Resin
Strip
Manufacturer's
Association,
and
two
private
citizens,
Arturo
Haran
and
Eric
Levine.
Amvac
submitted
a
review
of
human
incident
data
for
Dichlorvos
(
Feiler
1995),
and
the
Japanese
Resin
Strip
Manufacturer's
Association
submitted
data
on
poisoning
incidences
involving
dichlorvos
resin
strips.
Arturo
Haran
submitted
an
anecdotal
report
of
health
effects
and
Eric
Levine
submitted
a
comment
about
the
Page
56
of
151
potential
carcinogenicity
of
dichlorvos.
The
Agency
has
reviewed
this
new
information
(
Blondell
1996).
The
Agency's
conclusions
are
summarized
below.

Data
reported
by
the
American
Association
of
Poison
Control
Centers
(
AAPCC)
concerning
exposure
to
single
products
with
dichlorvos
often
contain
other
active
ingredients.
AAPCC
reported
21,006
exposures
to
single
products
containing
dichlorvos.
Most
of
these
exposures
involve
homeowner
use
products
that
contained
dichlorvos
in
combination
with
other
insecticides
such
as
propoxur,
pyrethrins,
or
piperonyl
butoxide.
In
these
cases
involving
dichlorvos
in
combination
with
other
pesticides
it
is
incorrect
to
attribute
any
resulting
toxicity
solely
to
dichlorvos.

Dichlorvos
resin
strips
account
for
a
very
small
proportion
of
total
incidents,
about
33
cases
per
year
(
1%
of
total
incidences).
Incident
reports
involving
exposure
to
resin
strips
usually
do
not
involve
any
significant
acute
symptoms
that
would
require
medical
treatment
(
Blondell
1996).

Eric
Levine
commented
on
epidemiological
evidence
linking
use
of
dichlorvos
resin
strips
with
childhood
cancer.
Two
epidemiologic
studies
have
reported
an
association
between
exposure
to
dichlorvos
resin
strips
and
childhood
cancer.
These
studies
by
Liess
and
Savitz
(
1995)
and
Davis
et
al
(
1993)
have
been
reviewed
by
the
Agency
(
Blondell
1996).
Reviews
of
these
studies
have
identified
biases
and
confounders
that
could
explain
the
observed
associations.
The
Agency
concludes
that
the
biases
are
a
more
likely
explanation
for
the
findings
of
increased
cancer
than
exposure
to
resin
strips.
Additional
studies
that
correct
for
the
control
of
potential
biases
and
problems
of
exposure
determination
are
needed
before
an
association
between
dichlorvos
and
childhood
cancer
can
be
established.

A
statistically
significant
excess
risk
for
prostate
cancer
and
dichlorvos
exposure
was
reported
in
the
recent
Agricultural
Health
Study
(
AHS)
by
Alavanja
et
al.,
(
2003).
The
reported
excess
risk
was
based
on
a
small
number
of
cases
(
n=
16)
and
only
seen
in
the
men
who
had
a
family
history
of
prostate
cancer.
The
odds
ratio
reported
was
1.75,
(
75%
excess)
with
confidence
interval
1.0­
3.06,
meaning
the
risk
could
be
as
high
as
206%.
Dichlorvos
was
one
of
seven
chemicals
positive
for
prostate
cancer
among
fifty
chemicals
tested.
There
is
no
AHS
chemical
specific
report
on
dichlorvos
at
this
time.
Follow­
up
studies
are
planned
to
examine
the
interaction
effect
on
family
history
and
genetic
susceptibility
factors.
The
AHS
is
a
prospective
pesticide
epidemiology
study
that
includes
over
90,000
certified
pesticide
applicators
and
their
families
from
Iowa
and
North
Carolina.
Additional
analyses
will
examine
dichlorvos
findings,
as
part
of
the
high
pesticide
exposure
event
studies
and
work
practices
assessments.
Dichlorvos
is
not
one
of
the
current
National
Health
and
Nutrition
Examination
Surveys
(
NHANES)
chemicals
being
examined
by
the
Centers
for
Disease
Control
(
CDC)
National
Center
for
Health
Statistics
(
NCHS).
Page
57
of
151
6.0
Exposure
Characterization/
Assessment
6.1
Dietary
Exposure/
Risk
Pathway
6.1.1
Residue
Profile
The
reregistration
requirements
for
plant
and
livestock
metabolism
are
fulfilled.
The
Agency
determined
that
the
available
data
depicting
the
metabolism
of
naled
in
plants
are
sufficient
to
delineate
the
metabolism
of
dichlorvos
in
plants
because
dichlorvos
is
the
initial
metabolite
of
naled.
In
plants,
naled
is
metabolized
to
dichlorvos
which
is
hydrolyzed
to
dimethyl
phosphate
and
dichloroacetaldehyde.
Dimethyl
phosphate
is
sequentially
degraded
to
monomethyl
phosphate
and
inorganic
phosphates,
and
dichloroacetaldehyde
is
converted
to
2,2­
dichloroethanol
which
is
then
conjugated
and/
or
incorporated
into
naturally
occurring
plant
components.
The
residue
of
concern
in
plant
commodities
is
dichlorvos.

Acceptable
studies
depicting
the
qualitative
nature
of
the
residue
in
ruminants
and
poultry
following
dermal
treatment
with
dichlorvos
have
been
submitted
and
evaluated.
Because
dichlorvos
is
the
initial
metabolite
of
naled,
the
available
metabolism
studies
reflecting
oral
dosing
of
ruminants
and
hens
with
naled
are
sufficient
to
delineate
the
metabolism
of
orally
dosed
dichlorvos
in
animals.
The
residue
of
concern
in
animal
commodities
is
dichlorvos.

Adequate
field
trial
and
processing
data
are
available
for
the
reregistration
of
dichlorvos,
although
not
all
the
field
trial
data
are
adequately
supported
by
storage
stability
data,
and
there
is
an
outstanding
data
requirement
for
a
dermal
study
in
swine.
Finite
residues
are
reported
in
the
field
trials,
but
residues
are
generally
non­
detectable
in
monitoring
data.
Non­
detectable
residues
were
generally
reported
in
livestock
tissues,
milk,
and
eggs.
Adequate
enforcement
analytical
methods
are
available
in
PAM
I
and
II.
Dichlorvos
is
recovered
by
PAM
I
Luke
multiresidue
method
(
protocol
D),
provided
"
early
eluter"
conditions
are
used.
The
Pesticide
Analytical
Manual
(
PAM)
Vol.
II
lists
a
GC
method
(
with
flame
photometric
detection;
Method
I)
for
the
determination
of
dichlorvos
in
plant
and
animal
commodities.
An
additional
GC
method
(
Method
II)
using
electron
capture
detection
is
listed
for
the
determination
of
dichlorvos
and
naled
in
plant
and
animal
commodities;
this
method
is
also
an
enforcement
method
for
naled.
A
GC
method
using
microcoulometric
detection
is
listed
as
Method
A.
This
method
determines
total
residues
of
dichlorvos
and
naled
via
conversion
of
naled
residues
to
dichlorvos;
however,
the
method
can
be
modified
to
determine
naled
and
dichlorvos
separately.
Data
collection
methods
were
similar
to
the
available
enforcement
methods,
and
were
adequately
validated.

Dietary
exposure
to
dichlorvos
residues
may
occur
as
a
result
of
use
on
or
at
a
variety
of
sites,
including
mushroom
houses,
warehouses
containing
bulk­
stored
and
packaged
or
bagged
nonperishable
processed
and
raw
food,
commercial
food
processing
plants,
groceries,
direct
animal
treatment,
and
livestock
premise
treatment.
As
a
result,
dichlorvos
residues
may
be
found
in
bulk
stored
and
packaged
or
bagged
non
perishable
processed
or
raw
food.
Dichlorvos
residues
may
also
be
found
in
mushrooms
and
in
livestock
commodities,
such
as
meat,
milk,
meat
byproducts,
poultry,
and
eggs.
In
addition,
a
dichlorvos
registrant
has
expressed
interest
in
supporting
use
on
tomatoes.
Page
58
of
151
Two
other
pesticides,
naled
and
trichlorfon,
degrade
to
dichlorvos
through
plant
and
livestock
metabolism,
and
non­
biological
reactions.
The
Agency
does
not
expect
measurable
dichlorvos
residues
from
trichlorfon
because
all
trichlorfon
food
uses
on
field
crops
have
been
canceled
and
associated
tolerances
revoked,
and
non­
detectable
residues
were
found
in
livestock
dermal
studies.

Three
factors
will
significantly
affect
dietary
exposure
to
dichlorvos
from
registered
uses
of
naled;
these
include
the
pre­
harvest
interval
(
PHI),
the
condition
and
length
of
storage,
and
cooking
and
processing.
Plant
metabolism
studies
show
that
dichlorvos
residues
are
formed
1
to
3
days
after
treatment
with
naled;
however,
dichlorvos
residues
decline
to
less
than
the
limit
of
detection
(
0.01
to
0.05
ppm)
7
days
after
treatment.
In
general,
registered
uses
of
naled
have
PHIs
of
less
than
7
days.
Because
of
the
short
PHIs
for
naled
products,
measurable
residues
of
dichlorvos
may
be
present
in
the
diet
from
naled
treated
food.
As
a
result,
the
dietary
(
food)
exposure
assessment
for
dichlorvos
includes
residues
of
dichlorvos
resulting
from
the
application
of
naled.

Dietary
exposure
estimates
for
acute
and
chronic
dietary
exposure
assessments
have
been
refined
with
residue
data
from
USDA's
Pesticide
Data
Program
(
PDP),
FDA
surveillance
monitoring
data,
and
FDA
Total
Diet
Study
(
TDS)
data,
processing
and
cooking
studies,
and
percent
of
crop
treated
information.

Sources
of
data
to
estimate
the
levels
of
residues
of
pesticides
in
food
include
the
following:
tolerances
(
legal
limits),
controlled
field
trial
data,
Food
and
Drug
Administration
(
FDA)
surveillance
and
compliance
monitoring
data,
FDA
Total
Diet
Study
data
(
market
basket
survey
based
on
a
random
sampling
of
residues
on
food
in
grocery
stores),
US
Department
of
Agriculture
(
USDA)
Pesticide
Data
Program
(
PDP),
and
USDA/
FSIS
(
Food
Safety
Inspection
Service)
livestock
monitoring
data
(
Hummel,
1998a,
Hummel
2000).
The
estimated
levels
of
residues
can
then
be
adjusted
for
the
effects
of
processing
using
processing
studies,
including
commercial
processing
studies,
washing
studies,
cooking
studies,
and
residue
degradation
studies.
Of
these
sources,
the
Agency
relied
on
tolerance
levels
and
field
trial
data
(
adjusted
for
the
effects
of
processing
and
cooking)
to
estimate
dietary
exposure
to
dichlorvos
in
the
PD
2/
3.
At
the
time
of
the
PD
2/
3,
the
monitoring
data
available
for
dichlorvos
were
very
limited.
In
this
updated
assessment,
anticipated
residues
based
on
some
tolerances
plus
field
trial
and
monitoring
data
were
used.

(
a).
Field
Trial
Data.
Data
from
controlled
field
trials
which
reflect
currently
registered
uses
are
available
for
mushrooms.
Data
from
direct
dermal
treatments
to
cattle
and
poultry
are
discussed
in
the
Dichlorvos
Registration
Standard.
Field
trial
data
are
available
for
packaged
or
bagged
food,
use
in
food
manufacturing
and
processing
facilities,
and
for
secondary
residues
in
livestock
commodities.
Adequate
field
trial
data
are
not
available
for
tomatoes.

(
b).
FDA
Surveillance
and
Compliance
Monitoring
Data.
The
FDA
Surveillance
and
Compliance
Monitoring
Program
is
designed
to
ensure
that
pesticide
residues
do
not
exceed
established
tolerances.
Naled
and
dichlorvos
are
included
in
the
FDA
surveillance
and
compliance
monitoring
programs.
However,
dichlorvos
is
only
detected
using
the
Luke
method
on
non­
fatty
foods,
and
only
when
"
early
eluter"
column
conditions
are
used
(
low
column
temperature).
Thus,
the
number
of
samples
analyzed
for
dichlorvos
is
low
compared
to
the
samples
analyzed
for
other
Page
59
of
151
pesticides,
although
the
number
of
analyses
done
by
FDA
that
will
detect
dichlorvos
have
increased
significantly
in
the
last
few
years.
FDA
Surveillance
and
Compliance
monitoring
data
were
obtained
from
FDA
for
1990
through
1998.
From
1994
through
1998,
FDA
analyzed
over
3000
surveillance
monitoring
samples
for
dichlorvos.
The
limit
of
quantitation
(
LOQ)
for
dichlorvos
in
fruits
and
vegetables
is
approximately
0.01
ppm,
and
the
limit
of
detection
(
LOD),
approximately
0.003
ppm.

All
residues
of
dichlorvos
reported
were
non­
detectable,
with
the
following
exceptions:
three
samples
of
strawberries
(
which
had
low
levels
of
detectable
residues
of
dichlorvos),
one
sample
of
red
raspberries
(
0.08
ppm
dichlorvos);
one
tomato
sample
from
Mexico
with
a
trace
residue
(>
LOD,
but
<
LOQ);
one
sample
of
garbanzo
beans
from
S.
Korea
with
a
trace
residue;
and
0.03
ppm
on
one
sample
of
cantaloupe
from
Honduras.
All
residues
of
naled
reported
were
non­
detectable,
with
the
following
exceptions:
3
samples
of
strawberries
with
residues
of
0.1,
0.2,
and
0.43
ppm
naled.

(
c).
FDA
Total
Diet
Study
Data
(
TDS).
The
FDA
Total
Diet
Study
Program
is
designed
to
measure
trends
in
pesticide
residues.
Since
1982,
approximately
four
market
baskets
per
year
have
been
collected
in
a
large
city
in
one
of
four
regions
of
the
country.
The
region
of
the
country
in
which
the
market
basket
samples
are
collected
rotates
so
that
samples
are
collected
in
all
four
regions
over
one
year.
FDA
summarizes
the
data
expressed
as
daily
intakes
for
8
age­
sex
groups
(
infants,
young
children,
male
and
female
teenagers,
male
and
female
adults,
and
male
and
female
older
persons).
Each
market
basket
has
consisted
of
234­
265
individual
food
items
prepared
as
ready
to
eat
foods
(
washed
and
cooked).
Individual
foods
are
analyzed
separately.
Although
the
TDS
includes
sampling
of
meats
and
poultry,
dichlorvos
could
not
be
analyzed
in
these
commodities
using
the
TDS
analytical
methods.

Historically,
the
Agency
has
not
used
FDA
Total
Diet
Study
data
for
exposure
assessment
purposes
because
the
number
of
samples
is
limited
(
approximately
four
samples
per
year
of
each
of
234
­
265
individual
food
items
since
1982),
samples
are
only
collected
in
large
cities,
and
the
treatment
history
is
unknown.
The
TDS
does
not
include
minor
crops.
However,
a
total
of
43
market
basket
surveys
are
now
available
for
1982
­
1996.
Among
the
commodities
collected
in
the
TDS,
there
were
approximately
35
non­
fatty
commodities
analyzed
which
were
similar
to
crackers
and
cereals,
approximately
11
baked
goods
which
were
made
from
flour,
sugar,
and
dried
eggs,
4
coffee
and
1
tea
commodities,
plus
raisins,
prunes,
and
cooked
eggs.
These
are
commodities
that
are
or
are
produced
from
`
bulk
stored'
and
`
packaged
and
bagged'
commodities,
and
may
have
been
treated
with
dichlorvos
closer
to
the
point
of
consumption
than
the
wheat
grain
samples
collected
by
USDA
in
their
Pesticide
Data
Program.

By
grouping
the
commodities
(
generally
along
crop
group
classifications),
there
were
more
than
100
samples
per
group
of
commodities
analyzed.
The
Agency
has
used
extrapolation
among
members
of
crop
groups
in
the
past
when
using
monitoring
data.
For
example,
monitoring
data
for
oranges
could
be
extrapolated
to
all
citrus
(
tangerines,
tangelos,
grapefruit,
lemons,
and
limes),
provided
the
use
pattern
for
citrus
is
the
same.

Dichlorvos
is
not
listed
specifically
as
one
of
the
pesticides
recovered
in
the
analyses
for
the
FDA
Total
Diet
Study.
However,
all
of
the
Total
Diet
Study
samples
were
analyzed
using
Page
60
of
151
temperature
programming
which
would
allow
detection
of
"
early
eluters."
Therefore,
if
dichlorvos
is
present,
it
would
be
detected,
and
one
detectable
residue
of
dichlorvos
was
reported.
The
LOD
for
dichlorvos
in
total
diet
samples
is
0.001
ppm
(
personal
communication,
B.
McMahon,
FDA).

(
d).
USDA
Pesticide
Data
Program
Data.
The
USDA
Pesticide
Data
Program
(
PDP)
collects
residue
data
primarily
for
fresh
fruits
and
vegetables,
plus
wheat
grain,
beef
commodities,
poultry
commodities,
and
milk.
A
few
canned
and
frozen
commodities
have
been
tested.
Samples
are
collected
in
terminal
markets
and
large
distribution
centers.
The
commodities
included
in
the
PDP
changes
annually.
Sampling
dates
and
sites
are
selected
at
random
following
a
statistically
designed
sampling
plan.
Participating
laboratories
meet
rigorous
quality
assurance/
quality
control
(
QA/
QC)
criteria
including
following
good
laboratory
practices
(
GLP),
a
check
sample
program,
and
confirmation
of
residue
findings.
Sampling
and
analyses
are
done
through
a
cooperative
agreement
with
nine
states
and
two
USDA
laboratories.
These
states
represent
about
50%
of
the
population
of
the
US
and
a
large
percentage
of
the
fresh
fruits
and
vegetables
grown
in
the
US.
Food
commodities
collected
in
the
PDP
are
prepared
as
normally
would
be
done
for
consumption,
washed
and
peeled,
although
not
cooked.
Canned
and
frozen
commodities
are
not
further
cooked
before
analysis,
although
they
may
have
been
blanched
or
cooked
in
the
canning
or
freezing
process.

The
USDA
PDP
analyzes
for
dichlorvos,
which
would
include
dichlorvos
resulting
from
naled
since
the
analytical
method
used
generally
converts
naled
to
dichlorvos
prior
to
or
during
the
analysis.
The
LOD
for
the
analyses
varied,
depending
on
the
laboratory
conducting
the
analyses,
and
ranged
from
3
ppb
to
280
ppb.
All
samples
analyzed
for
dichlorvos
had
non­
detectable
residues,
except
for
(
1)
one
peach
sample
analyzed
in
1992,
which
had
a
dichlorvos
residue
of
0.059
ppm;
(
2)
one
green
bean
sample
analyzed
in
1994,
which
had
a
dichlorvos
residue
of
0.012
ppm;
(
3)
one
grape
sample
analyzed
in
1996,
which
had
a
dichlorvos
residue
of
0.003
ppm,
which
was
below
the
LOQ;
(
4)
one
milk
sample
analyzed
in
1996,
which
had
a
dichlorvos
residue
of
0.003
ppm,
which
was
below
the
LOQ;
(
5)
one
pear
sample
analyzed
in
1997,
which
had
a
dichlorvos
residue
of
0.005
ppm,
which
was
below
the
LOQ;
and
(
5)
15
strawberry
samples
in
1998,
on
which
the
maximum
dichlorvos
residue
was
0.02
ppm.
PDP
data
were
used
in
the
dichlorvos
dietary
exposure
assessment
for
commodities
which
could
be
treated
with
naled,
beef
commodities,
poultry
commodities,
and
for
milk.
The
PDP
data
on
wheat
grain
were
not
used,
because
packaged
and
bagged
commodities
made
from
wheat
grain
could
have
been
treated
again
with
dichlorvos
after
the
PDP
samples
would
have
been
collected.
The
PDP
does
not
analyze
for
naled
because
initial
method
validation
indicated
that
naled
is
converted
to
dichlorvos
during
the
analysis.
The
PDP
does,
however,
identify
unknown
residues,
and
would
report
a
residue
of
naled
if
found.

(
e).
Processing
and
Cooking
Study
Data.
Residues
for
raw
commodities
can
be
modified
by
processing
factors
to
account
for
changes
during
commercial
or
other
processing
and
cooking.
Processing,
cooking
and
decline
(
half­
life)
studies
were
available
for
cocoa
beans,
dry
pinto
beans,
tomato
juice,
ground
roasted
coffee
beans,
raw
hamburger
meat,
raw
eggs,
and
raw
whole
milk.
The
resulting
cooking
factors
were
used
to
reduce
the
Agency's
estimate
of
residues
for
these
commodities
and
were
translated
to
other
commodities
based
on
similarity
of
cooking
time
and
temperature.
Additional
cooking
studies
were
available
and
discussed
in
the
Residue
Chemistry
Chapter
of
the
Registration
Standard.
Half­
lives
of
dichlorvos
in
various
commodities
ranged
from
0
Page
61
of
151
to
over
1,000
hours.
The
reduction
of
dichlorvos
upon
cooking
appeared
to
be
related
to
the
length
of
time
and
temperature
used
in
cooking.
Residues
were
adjusted
based
on
these
cooking
factors
to
obtain
the
Anticipated
Residue
Estimate
for
the
cooked
commodity.

(
f).
Percent
of
crop
treated
data.
OPP
has
refined
its
estimates
of
dietary
exposure
for
various
commodities
based
on
percent
of
crop
treated.
The
Biological
and
Economic
Analysis
Division
(
BEAD)
of
OPP
provided
updated
percent
of
crop
treated
(%
CT)
information
that
were
incorporated
into
the
acute
dietary
(
food)
exposure
analysis
as
appropriate
(
Hummel,
et.
al.
2000).
Where
a
range
of
percent
crop
treated
estimates
are
supplied
for
this
analysis,
the
upper
end
of
that
range
is
assumed
for
acute
dietary
(
food)
exposure
analysis,
and
the
typical
or
average
%
CT
is
used
for
the
chronic
dietary
(
food)
exposure
analysis.

6.1.2
Acute
and
Chronic
Dietary
Exposure
and
Risk
Anticipated
residues
are
a
realistic
estimate
of
actual
pesticide
residues
in
foods
based
on
available
data.
Reliable
data
are
available
for
dichlorvos,
including
the
USDA's
PDP
data,
the
FDA
Total
Diet
Study
and
the
FDA
monitoring
data.
These
data
were
not
available
at
the
time
of
the
PD
2/
3,
Notice
of
Intent
to
Cancel,
published
in
1995.
Anticipated
residues
used
in
the
dietary
risk
assessment
are
presented
in
separate
memo
(
Hummel
S,
Hrdy
D,
and
Sahafayen
M,
2000).
The
methods
for
deriving
anticipated
residues
for
dichlorvos
are
described
below.

(
a)
From
Use
of
Dichlorvos.
All
dichlorvos
tolerances
in
40
CFR
§
180.235
were
evaluated
as
potential
sources
of
dichlorvos
residues.
For
the
updated
dichlorvos
dietary
exposure
assessment,
FDA
Total
Diet
Study
data
were
used
for
residues
resulting
from
the
use
of
dichlorvos
per
se,
where
appropriate,
by
grouping
similar
commodities
made
from
grain
products,
sugar,
dried
eggs,
coffee
and
tea,
and
dried
fruits.
These
are
summarized
below.

Raw
Agricultural
Commodities.
The
following
uses
have
been
canceled
by
AMVAC:
tomatoes,
cucumbers,
lettuce,
and
radishes,
and
the
associated
tolerances
recommended
for
revocation.
Therefore,
these
uses
are
not
included
in
the
exposure
assessment.
One
dichlorvos
registrant
has
proposed
supporting
use
on
tomatoes,
and
tomatoes
still
appears
on
one
product
label,
EPA
Reg.
No.
5011­
49.
No
residue
data
were
provided
to
support
this
use.
No
detectable
residues
of
dichlorvos
were
detected
on
tomatoes
in
1996­
1998
in
the
PDP
or
from
1994­
1998
in
the
FDA
Surveillance
Monitoring
Program.

Meat,
Milk,
Poultry
and
Eggs.
Residues
in
livestock
tissues,
including
milk
and
eggs,
may
result
from
consumption
of
dichlorvos
treated
livestock
feeds,
direct
dermal
treatments,
livestock
premise
treatments,
or
from
use
as
a
drug
in
swine.
Livestock
metabolism
studies
done
at
exaggerated
rates
in
ruminants
and
poultry
have
demonstrated
that
oral
ingestion
of
dichlorvos,
naled,
and
trichlorfon
by
cattle
and
poultry
will
not
result
in
detectable
residues.
This
conclusion
can
be
translated
to
the
drug
use
of
dichlorvos
in
swine.
Secondary
residues
in
livestock
and
poultry
from
consumption
of
treated
feed
fall
under
category
3
of
40
CFR
§
180.6(
a),
having
no
reasonable
expectation
of
finite
residues.
Data
reflecting
dichlorvos
direct
livestock
treatments
are
discussed
in
the
Residue
Chemistry
Chapter
of
the
Dichlorvos
Registration
Standard.
Data
from
direct
dermal
studies
indicate
that
detectable
residues
are
not
expected,
except
in
skin.
Residues
are
non
Page
62
of
151
detectable
(<
0.01
ppm)
in
cattle
tissue
and
milk,
and
non­
detectable
(<
0.05
ppm)
in
poultry
tissues
and
eggs.
For
the
PD
2/
3
dietary
exposure
assessment,
the
Agency
used
one­
half
the
limit
of
detection
as
the
residue
estimate
in
both
cases.

PDP
monitoring
data
were
available
for
meat
(
beef
and
poultry)
commodities,
and
milk.
Nondetectable
residues
of
dichlorvos
were
found
in
all
beef
commodities
(<
0.001
ppm)
and
poultry
commodities
(<
0.006
ppm),
Ratios
of
dichlorvos
residues
found
in
livestock
tissues
in
dermal
metabolism
studies
to
residues
of
dichlorvos
found
in
milk
in
the
livestock
dermal
metabolism
studies
were
calculated.
These
ratios
were
then
used
with
the
PDP
monitoring
data
in
milk
to
estimate
residues
of
dichlorvos
in
livestock
tissues
(
lower
than
the
PDP
limit
of
quantitation
for
beef
commodities).
The
dietary
exposure
estimates
in
poultry
commodities
are
based
on
the
nondetectable
residues
(<
0.006
ppm)
reported
in
PDP
monitoring
data.
A
cooking
factor
of
0.3x
was
then
applied.
The
dietary
exposure
estimate
for
eggs
was
the
non­
detectable
residue
found
in
cooked
eggs
in
the
FDA
Total
Diet
Study.

Bulk
Stored,
Packaged
or
Bagged
Commodities,
Food
and
Feed
Handling
Uses.
The
anticipated
residues
used
in
the
Dichlorvos
PD
2/
3
exposure
assessment
for
packaged,
bagged
or
bulk
stored
food
were
based
on
field
studies
submitted
by
AMVAC
(
Hummel
1994b).
Residue
data
were
submitted
for
many
commodities.
For
those
commodities
where
data
were
not
submitted,
the
Agency
translated
residue
data
from
similar
commodities.
For
example,
data
on
dry
beans
are
translated
to
other
legumes;
data
on
wheat
flour
are
translated
to
all
flours
and
meals,
etc.
In
addition,
residue
data
were
provided
for
corn
and
oats
at
various
points
during
processing,
and
for
flour,
sugar,
dried
milk,
dried
eggs,
shortening,
and
baking
mix
from
a
treated
manufacturing
facility.
Bulk
stored
commodities
are
assumed
to
be
uncovered
when
treated.
Although
pesticide
labels
state
that
bulk
or
unpackaged
foods
should
be
covered
or
removed
before
spraying,
it
is
not
possible
to
assess
the
effect
of
covering
food
since
the
type
of
material
used
in
the
cover
is
not
specified
and
the
manner
in
which
food
is
covered
would
vary
considerably.
Therefore,
food
is
assumed
to
be
uncovered,
which
is
likely
to
overestimate
residues.
Since
the
proportion
of
commodities
stored
in
bulk
vs.
packaged/
bagged
is
unknown,
the
anticipated
residues
are
based
the
residues
found
in
packaged/
bagged
food,
because
foods
are
expected
to
be
packaged/
bagged
closer
to
the
time
of
consumption.

FDA
TDS
data
were
used
for
the
dichlorvos
dietary
exposure
assessment
on
grain
products
and
sugar,
eggs,
coffee
and
tea.
In
the
43
samples
of
126
commodities
in
which
dichlorvos
would
be
detected,
only
one
sample
had
a
detectable
residue,
one
sample
of
rye
bread
at
0.01
ppm,
which
is
below
the
LOQ
of
0.03
ppm.

The
tolerances
in
40
CFR
§
180.235
for
nonperishable
packaged,
bagged
or
bulk
raw
food
and
for
packaged
or
bagged
nonperishable
processed
foods
(
formerly
in
40
CFR
§
185.1900)
do
not
refer
to
specific
commodities.
Therefore,
the
Agency
has
developed
a
list
of
commodities
likely
to
be
treated
with
dichlorvos
that
are
covered
by
tolerances.
Because
these
tolerances
were
established
to
cover
residues
resulting
from
use
at
different
sites
(
for
example,
wheat
could
be
treated
in
its
raw
form
in
a
silo,
later
as
flour,
during
processing
into
cake
mixes,
and
finally
as
a
stored
packaged
commodity),
cancellation
of
any
one
of
the
site­
specific
uses
does
not
necessarily
eliminate
the
risk
of
a
commodity
from
dichlorvos
treatment.
The
Agency
did
not
combine
the
residues
from
different
Page
63
of
151
sites
in
creating
the
anticipated
residues,
although
the
cumulative
residues
from
treating
a
commodity
at
different
sites
were
considered
in
the
estimation
of
percent
of
crop
treated
for
the
PD
2/
3;
however,
the
Agency
position
has
changed.
Now
we
expect
that
sufficient
time
will
pass
between
treatments
that
only
the
maximum
residue
from
one
type
of
treatment
needs
to
be
considered.

(
b)
From
Use
of
Naled.
All
naled
tolerances
in
40
CFR
§
180.215
were
evaluated
as
potential
sources
of
dichlorvos
residues.
Anticipated
residues
are
based
on
either
tolerance
level
equivalents
or
field
trials
or
monitoring
data
from
FDA
(
Regulatory
monitoring
or
Total
Diet
Study)
or
USDA
(
PDP).
These
data
sources
were
used
for
both
acute
and
chronic
dietary
exposure
estimates.
Naled
and
dichlorvos
residue
estimates
were
reduced
when
data
were
available
to
account
for
the
effects
of
washing,
cooking,
and
processing.
In
addition,
wide
area
application
of
naled
in
mosquito
and
fly
control
use
could
result
in
residues
potentially
on
all
crops
in
the
Agency's
DEEM
 
software.
The
Agency
did
not
include
all
these
crops
in
its
estimate
of
anticipated
dichlorvos
residues
for
the
chronic
dietary
exposure
assessment.
Although
it
is
possible
that
dichlorvos
residues
could
occur
on
any
raw
agricultural
commodity
from
this
use
of
naled,
it
is
unlikely
that
residues
would
be
found
on
all
commodities.
As
a
result,
this
inclusion
of
residues
of
dichlorvos
from
all
raw
crops
would
present
a
possible
source
of
overestimation
of
dietary
exposure.
A
sensitivity
analysis
was
conducted
for
naled
and
dichlorvos
from
naled,
done
separately
from
the
dichlorvos
risk
assessment,
showing
that
the
mosquito
and
fly
control
use
was
not
a
substantial
source
of
exposure.

(
c)
From
Use
of
Trichlorfon.
All
trichlorfon
tolerances
in
40
CFR
180.198
were
evaluated
as
a
potential
source
of
dichlorvos
residues.
All
tolerances
for
trichlorfon
have
been
revoked,
with
the
exception
of
tolerances
in
beef
cattle
commodities,
which
are
being
retained
to
cover
potential
residues
from
imported
meat
commodities.
In
trichlorfon
cattle
feeding
studies,
residues
of
trichlorfon
and
dichlorvos
were
non­
detectable
(<
0.05
ppm)
in
livestock
commodities
at
preslaughter
intervals
of
1,
3,
and
7
days
(
T.
Morton,
1999).
This
would
result
in
residue
estimates
of
the
same
order
of
magnitude
as
those
for
dichlorvos
alone
and
naled­
derived
dichlorvos.
Measurable
residues
of
dichlorvos
from
the
use
of
trichlorfon
are
not
expected,
because
it
has
no
crop
tolerances
or
registered
crop
food
uses
(
Hummel,
1998b),
and
non­
detectable
residues
are
expected
on
livestock
commodities.

6.1.2.1
Acute
Dietary
Exposure
and
Risk
A
DEEM
 
analysis
was
performed
to
estimate
acute
dietary
exposure
and
risk
from
dichlorvos;
and
to
estimate
dietary
exposures
and
risks
for
chronic
systemic
toxicity
from
residues
of
dichlorvos
(
Hummel,
S.
V.,
D.
Hrdy,
M.
Sahafayen.
2000).
Because
dichlorvos
residues
on
food
may
be
derived
from
use
of
either
dichlorvos
or
naled,
the
dietary
risk
analyses
included
both
dichlorvos
and
naled­
derived
dichlorvos.
Trichlorfon­
derived
dichlorvos
was
considered.
All
domestic
field
crop
uses
of
trichlorfon
have
been
canceled.
The
trichlorfon
tolerances
have
been
revoked,
except
for
tolerances
in
livestock
commodities,
which
were
retained
as
import
uses.
The
DEEM
 
analyses
were
done
for
all
commodities
supported
for
reregistration.

A
highly
refined
acute
dietary
analysis
was
performed,
which
combined
the
acute
exposure
from
dichlorvos
residues
resulting
from
the
use
of
dichlorvos,
naled­
derived
dichlorvos
(
including
Page
64
of
151
residues
of
naled,
which
could
be
converted
in
the
body
to
dichlorvos),
but
excluding
the
naled
public
health
mosquito
use
(
Hummel,
et.
al.
2000).
Residues
of
dichlorvos
from
the
use
of
trichlorfon
were
estimated
to
be
negligible.
For
assessing
risk
use
of
dichlorvos,
anticipated
residues
based
on
field
trials
and
monitoring
data
were
used.
For
assessing
risk
from
naled­
derived
dichlorvos,
anticipated
residues
based
on
some
tolerances,
some
field
trials,
and
monitoring
data
were
used.
The
acute
probabilistic
dietary
analyses
used
individual
food
consumption
as
reported
by
respondents
in
the
USDA
1989­
91
Continuing
Survey
of
Food
Intake
by
Individuals
(
CSFII)
in
the
DEEM
 
software.
Results
are
reported
as
a
percentage
of
the
aPAD
for
the
99.9th
percentile
of
the
population.
The
%
aPAD
is
calculated
as
the
ratio
of
the
exposure
to
the
aPAD
(%
aPAD
=
exposure/
aPAD
x
100%).

Highly
refined
anticipated
residues
which
incorporated
percent
of
crop
treated
(%
CT),
monitoring
data
from
the
PDP,
the
FDA
Surveillance
Monitoring
Program,
the
FDA
TDS,
field
trial
data,
and
a
few
tolerances
were
used
to
estimate
acute
dietary
exposure.
The
acute
exposure/
risk
estimate
did
not
exceed
HED's
level
of
concern
for
either
the
general
US
population
or
any
of
the
sub­
populations.
The
sub­
population
with
the
highest
exposure
was
children
1­
6
with
estimated
exposure
of
4%
of
the
aPAD
(
0.000021
mg
dichlorvos/
kg
bwt/
day),
while
the
estimated
exposure
for
the
U.
S.
Population
was
2%
of
the
aPAD
(
0.000009
mg
dichlorvos/
kg
bwt/
day)
at
the
99.9th
percentile.
The
results
are
provided
in
Table
6.2.1.1.

Table
6.1.2.1.
Acute
Dietary
(
Food
Only)
Tier
3
Exposure
and
Risk
Estimates
for
Dichlorvos.

95th
Percentile
99th
Percentile
99.9th
Percentile
Population
Subgroupa
aPAD,
mg/
kg
Exposure,
mg/
kg
%
aPADb
Exposure,
mg/
kg
%
aPADb
Exposure,
mg/
kg
%
aPADb
U.
S.
pop
­
all
seasons:
0.000018
0.23
0.000044
0.6
0.000145
1.8
All
infants
(<
1
year):
0.000022
0.28
0.000087
1.0
0.000308
3.8
Children
(
1­
6
years):
0.000034
0.43
0.000076
1.0
0.000334
4.2
Children
(
7­
12
years):
0.000022
0.28
0.000050
0.6
0.000167
2.1
Females
(
13­
50
years):
0.008
0.000013
0.16
0.000032
0.4
0.000085
1.1
a
Population
subgroups
shown
include
the
U.
S.
general
population,
and
those
of
infants,
children,
and
women
of
child­
bearing
age.
b
%
aPAD
=
Exposure
(
mg/
kg)
÷
aPAD
(
mg/
kg)
×
100
6.2.1.2.
Chronic
Dietary
Exposure
A
refined
DEEM
 
chronic
exposure
analysis
was
conducted
using
percent
crop
treated
data
and
anticipated
residues
to
calculate
the
chronic
dietary
exposure
estimate
for
the
general
population
and
all
subgroups
(
Hummel,
et.
al.
2000).
Anticipated
residues
were
based
on
monitoring
data
from
the
FDA
TDS,
the
FDA
Surveillance
Monitoring
Program,
and
from
the
PDP.
Therefore,
the
Agency
has
high
confidence
in
the
residue
data
used
to
estimate
chronic
dietary
exposure.

As
mentioned
above,
OPP
has
refined
its
estimates
of
dietary
exposure
for
various
commodities
based
on
percent
of
crop
treated.
OPP
has
refined
its
estimates
of
dietary
exposure
for
Page
65
of
151
various
commodities
using
processing
factors
to
account
for
changes
in
residue
levels
during
commercial
or
other
processing
and
during
cooking.
Page
66
of
151
Highly
refined
anticipated
residues
(
which
also
incorporated
%
CT
information,
monitoring
data
from
the
PDP
and
the
FDA
Surveillance
Monitoring
Program,
and
field
trial
data)
were
used
to
estimate
chronic
dietary
exposure.
The
chronic
exposure/
risk
estimate
did
not
exceed
HED's
level
of
concern
for
either
the
general
US
population
or
any
of
the
sub­
populations.
The
resulting
risk
estimate
for
all
sub­
populations
and
the
general
US
population
was
below
100%
of
the
cPAD.
The
sub­
population
with
the
highest
exposure
was
children
1­
6
with
1%
of
the
chronic
population
adjusted
dose
(
cPAD)
(
0.0000013
mg
dichlorvos/
kg
bwt/
day),
while
the
estimated
risk
to
the
U.
S.
Population
was
<
1%
of
the
cPAD
(
0.0000007
mg
residue/
kg
bwt/
day).
The
results
are
provided
below
in
Table
6.2.1.2.

Table
6.2.1.2.
Chronic
Dietary
(
Food
Only)
Tier
3
Exposure
and
Risk
Estimates
for
Dichlorvos.

Population
Subgroup
1
cPAD,
mg/
kg/
day
2
Exposure,
mg/
kg/
day
%
cPAD
U.
S.
Population
(
total)
0.0000007
<
1
All
infants
(<
1
year)
0.0000013
1
Children
1­
6
yrs
0.0000013
1
Children
7­
12
yrs
0.0000007
<
1
Females
13­
50
yrs
0.0005
0.0000003
<
1
1
Population
subgroups
shown
include
the
U.
S.
general
population,
and
those
of
infants,
children,
and
women
of
child­
bearing
age,
and
other,
representative
populations
whose
exposure
exceeds
that
of
the
U.
S.
general
population.
2
%
cPAD
=
Exposure
(
mg/
kg)
÷
cPAD
(
mg/
kg)
×
100
6.2.1.3.
Dietary
Cancer
Risk
Estimates
No
dietary
cancer
risks
for
dichlorvos
were
estimated.
The
carcinogenic
potential
of
dichlorvos
has
been
classified
as
"
suggestive"
under
the
1999
Draft
Agency
Cancer
Guidelines
and
no
quantitative
assessment
of
cancer
risk
is
required.
(
Diwan,
S.
2000).

6.2.2.
Uncertainties
in
Dietary
Exposure
Assessment
The
Agency
believes
the
exposure
and
risk
assessment
presented
in
this
document
is
the
most
refined
to
date
for
acute
and
chronic
dietary
exposure
to
dichlorvos
as
a
result
of
use
of
dichlorvos,
naled,
and
trichlorfon.
However,
there
are
some
uncertainties
associated
with
this
exposure
assessment
as
follows:

(
a).
The
dietary
exposure
analyses
relied
primarily
on
monitoring
data
obtained
either
"
at
the
farm
gate,"
in
the
case
of
FDA
surveillance
monitoring
data,
or
in
regional
distribution
warehouses
for
PDP
data.
Residues
potentially
present
on
items
purchased
at
roadside
produce
stands
or
farmer's
markets
are
not
represented
in
this
analysis.
Although
cooking
data
were
available
and
were
used,
there
may
be
differences
in
the
amount
of
reduction
of
dichlorvos
residues
as
a
result
of
cooking.
Page
67
of
151
(
b).
Samples
collected
for
the
FDA
Total
Diet
Study
were
collected
in
supermarkets
in
only
four
cities
per
year.
Residues
found
in
food
in
other
locations
may
be
different.

(
c).
Very
little
monitoring
data
are
available
for
fumigated
commodities.
Extensive
translation
was
done
from
one
fumigated
commodity
to
another.

(
d).
For
the
commodities
for
which
field
trial
data
were
used,
the
residues
of
dichlorvos
are
probably
over­
estimated.
Dichlorvos
is
expected
to
dissipate
fairly
rapidly.

6.2
Water
Exposure/
Risk
Pathway
Dichlorvos
residues
can
be
present
in
ground
and/
or
surface
water
as
a
result
of
use
of
three
pesticides:
dichlorvos
(
DDVP),
naled,
and
trichlorfon
(
dichlorvos
is
a
degradate
of
naled
and
trichlorfon).
The
Environmental
Fate
and
Effects
Division
(
EFED)
discussed
the
environmental
fate
of
dichlorvos,
naled
and
trichlorfon
and
evaluated
the
potential
for
dichlorvos
to
contaminate
water
from
these
sources
(
Abdel­
Saheb
I.,
2003,
Jones,
R.
D.,
2006).
The
environmental
fate
properties
of
dichlorvos,
naled,
and
trichlorfon
are
indicators
of
the
potentials
of
these
compounds
to
migrate
to
ground
or
surface
water.
These
fate
properties
are
described
below.

6.2.1
Fate
Properties
of
Dichlorvos,
Naled,
and
Trichlorfon
6.2.1.1.
Dichlorvos
The
major
mode
of
dissipation
of
dichlorvos
is
volatilization
from
soils
because
dichlorvos
has
a
vapor
pressure
of
1.2
X
10­
2
mm
Hg
under
field
conditions.
Also,
acceptable
laboratory
studies
indicate
rapid
dissipation
through
volatilization.
Dichlorvos
appears
to
degrade
through
aerobic
soil
metabolism
and
abiotic
hydrolysis
as
well,
but
these
processes
are
secondary
to
volatilization.
Hydrolysis
is
pH
dependent
where
the
half­
lives
were
11
days
at
pH
5,
5
days
at
pH
7
and
21
hours
at
pH
9.
Aerobic
soil
metabolism
data
showed
a
half­
life
of
10
hours;
2,2­
dichloroacetic
acid
was
the
major
metabolite.
An
acceptable
soil
TLC
study
indicates
that
dichlorvos
is
moderately
mobile
(
Kd's
ranging
0.3
to
1.2),
based
on
the
Heiling
and
Turner's
mobility
classification.
The
potential
of
dichlorvos
to
leach
to
ground
water
is
mitigated
by
its
rapid
degradation.
Dichlorvos
has
the
potential
to
contaminate
surface
waters
because
of
a
low
Koc
value
and
high
water
solubility
(
10
x
103
ppm,
or
1
%).
Substantial
fractions
of
run­
off
will
more
than
likely
occur
via
dissolution
in
run­
off
water
rather
than
adsorption
to
eroding
soil.
Despite
the
potential
for
contamination,
dichlorvos
should
not
be
persistent
in
any
surface
waters
due
to
its
susceptibility
to
rapid
hydrolysis
and
volatilization.

6.2.1.2.
Naled
Chemical
hydrolysis
and
biodegradation
are
the
major
processes
involved
in
the
transformation
of
naled
and
its
degradates
in
the
environment.
Dichlorvos
forms
from
naled
by
indirect
photolysis
in
water
and
soil.
In
the
presence
of
photosensitizer
in
water,
as
much
as
20%
of
the
applied
dose
of
naled
can
be
found
as
dichlorvos
after
1
day,
with
rapid
decline
of
dichlorvos
residues
afterwards.
Under
anaerobic
aquatic
conditions,
dichlorvos
can
be
as
high
as
15%
of
the
Page
68
of
151
applied
naled
dose
after
1
day.
The
degradation
of
dichlorvos
formed
from
naled
under
anaerobic
conditions
is
slower
(
half­
life
0.9
days)
than
under
aerobic
conditions.

6.2.1.3.
Trichlorfon
Dichlorvos
is
formed
from
trichlorfon
in
soil
by
aerobic
soil
metabolism,
and
in
water
hydrolysis
studies.
Environmental
fate
data
indicate
that
trichlorfon
degrades
rapidly
in
aerobic
soil
(
t1/
2
~
1.8
days)
under
non­
sterile
conditions;
however,
in
a
sterile
soil,
trichlorfon
was
stable
(
t1/
2
>
40
days).
Trichlorfon
degradation
is
strongly
influenced
pH.
In
the
hydrolysis
study
at
25
°
C,
the
trichlorfon
degradation
half­
life
was
104
days
at
pH
5;
34
hours
at
pH
7;
and
31
minutes
at
pH
9.
The
maximum
measured
dichlorvos
formed
from
trichlorfon
also
varied
with
pH,
with
a
maximum
percentage
converted
of
2.1%
at
pH
5;
25%
at
pH
7;
and
52%
at
pH
9.
The
formation
of
dichlorvos
from
trichlorfon
is
not
a
'
hydrolysis
reaction'
per
se,
but
a
dehydrochlorination.
The
other
degradates
found
in
the
hydrolysis
study
are
des­
methyldichlorvos,
and
dichloroacetaldehyde,
resulting
from
hydrolysis
of
dichlorvos
directly.
There
is
no
acceptable
field
dissipation
study
for
trichlorfon,
because
the
submitted
studies
had
recovery
problems.

6.2.2.
Groundwater
EFED
has
limited
monitoring
data
on
the
concentrations
of
dichlorvos,
naled
or
trichlorfon
in
groundwater.
Validated
monitoring
data
for
dichlorvos,
naled,
and
trichlorfon
are
available
for
the
states
of
California
and
Hawaii
from
the
Pesticides
in
Groundwater
Database
(
USEPA
1992).
These
data
indicated
that
naled,
dichlorvos,
or
trichlorfon
have
not
been
detected
in
groundwater.
However,
the
monitoring
studies
were
not
targeted
to
the
pesticide
use
area.
These
data
are
presented
in
Table
6.2.2a.
below.

Table
6.2.2a.
Groundwater
monitoring
data
for
Dichlorvos,
Naled,
and
Trichlorfon
showing
number
of
wells
sampled
(
number
of
wells
with
residues)
(
USEPA
1992)

Naled
Dichlorvos
Trichlorfon
California
83
(
0)
20(
0)
280
(
0)

Hawaii
3
(
0)
7
(
0)

Because
the
groundwater
monitoring
data
for
dichlorvos
are
limited,
EFED
used
the
Tier
I
SCI­
GROW
screening
model
to
estimate
concentrations
of
dichlorvos
in
groundwater.
This
model
predicts
that
dichlorvos,
naled,
and
trichlorfon
will
not
be
found
in
significant
concentrations
in
groundwater.
Concentrations
of
these
compounds
were
calculated
based
on
a
maximum
annual
application
rate
of
0.2
lb
a.
i./
acre
for
dichlorvos
(
wide
area
treatment),
9.375
lb
a.
i/
acre
for
naled
(
the
maximum
seasonal
use
rate
on
Cole
crops,
5
applications
of
1.87
lb
a.
i./
acre),
and
3
times
per
year
at
8.17
lb
a.
i./
acre
for
trichlorfon
(
turf).
The
amount
of
dichlorvos
formed
as
a
degradate
of
naled
was
estimated
to
be
20%
of
naled.
Therefore,
a
conservative
dichlorvos
use
rate
was
estimated
by
using
naled's
use
rate
multiplied
by
0.20.
The
amount
of
dichlorvos
formed
as
a
degradate
of
trichlorfon
was
estimated
to
be
56%
of
trichlorfon,
which
is
the
maximum
percent
of
dichlorvos
Page
69
of
151
(
56%)
formed
as
a
trichlorfon
degradate
determined
from
the
trichlorfon
aerobic
aquatic
metabolism
at
pH
8.5.
The
amount
of
dichlorvos
formed
as
a
trichlorfon
degradate
was
estimated
by
multiplying
the
maximum
application
rate
for
trichlorfon
(
8.17
lb
a.
i/
acre)
by
56%.
Because
groundwater
concentrations
of
dichlorvos
were
estimated
using
a
Tier
I
screening
model,
EFED
has
moderate
confidence
in
the
groundwater
assessment.

Table
6.2.2b.
Estimated
Dichlorvos
Concentrations
in
Groundwater.

Source
of
Dichlorvos
Residues
Modeled
Groundwater
Concentration,
µ
g/
L
Dichlorvos
Applied
1/
week
0.004
Dichlorvos
Applied
Every
Other
Day
0.015
Dichlorvos
(
from
Naled)
0.0002
Dichlorvos
(
from
Trichlorfon)
0.01
There
may
be
exceptional
circumstances
under
which
groundwater
concentrations
could
exceed
the
SCI­
GROW
estimates.
However,
such
exceptions
should
be
quite
rare
since
the
SCIGROW
model
is
based
exclusively
on
maximum
groundwater
concentrations
from
studies
conducted
at
sites
and
under
conditions
which
are
most
likely
to
result
in
groundwater
contamination.
The
groundwater
concentrations
generated
by
SCI­
GROW
are
based
on
the
largest
90­
day
average
recorded
during
the
sampling
period.
Since
there
is
relatively
little
temporal
variation
in
groundwater
concentrations
compared
to
surface
water,
the
concentrations
can
be
considered
as
appropriate
for
acute
and
chronic
risk
assessment.

6.2.3.
Surface
Water
Dichlorvos
may
reach
surface
water
as
a
result
of
use
of
three
pesticides:
dichlorvos
(
DDVP),
naled
and
trichlorfon.
In
the
event
that
all
of
these
pesticides
are
used
in
the
same
use
area,
then
the
contribution
for
each
chemical
should
be
incorporated
in
any
risk
assessment.

OPP
does
not
have
any
surface
water
monitoring
data
on
the
concentrations
of
dichlorvos,
naled,
or
trichlorfon
at
the
present
time.
Therefore,
the
Tier
II
PRZM/
EXAMS
model
was
used
for
dichlorvos,
naled
and
trichlorfon.
The
turf
scenario
with
the
Index
Reservoir
and
Percent
Crop
Area
adjustment
(
IR­
PCA
PRZM/
EXAMS)
was
used
to
estimate
surface
water
concentrations
for
trichlorfon.

The
results
from
the
index
reservoir
represent
potential
drinking
water
exposure
from
a
specific
area
(
Illinois)
with
specific
cropping
patterns,
weather,
soils,
and
other
factors.
Use
of
the
index
reservoir
for
areas
with
different
climates,
crops,
pesticides
used,
sources
of
water
(
e.
g.
rivers
instead
of
reservoirs,
etc),
and
hydrogeology
creates
uncertainties.
In
general,
because
the
index
reservoir
represents
a
fairly
vulnerable
watershed,
the
exposure
estimated
with
the
index
reservoir
Page
70
of
151
will
likely
be
higher
than
the
actual
exposure
for
most
drinking
water
sources.
However,
the
index
reservoir
is
not
a
worst
case
scenario;
communities
that
derive
their
drinking
water
from
smaller
bodies
of
water
with
minimal
outflow,
or
with
more
runoff
prone
soils
would
likely
get
higher
drinking
water
exposure
than
estimated
using
the
index
reservoir.
Areas
with
a
more
humid
climate
that
use
a
similar
reservoir
and
cropping
patterns
may
also
get
more
pesticides
in
their
drinking
water
than
predicted
using
this
scenario.

A
single
steady
flow
has
been
used
to
represent
the
flow
through
the
reservoir.
Discharge
from
the
reservoir
also
removes
chemical
so
this
assumption
will
underestimate
removal
from
the
reservoir
during
wet
periods
and
overestimates
removal
during
dry
periods.
This
assumption
can
underestimate
or
overestimate
the
concentration
in
the
pond
depending
upon
the
annual
precipitation
pattern
at
the
site.

The
index
reservoir
scenario
uses
the
characteristics
of
a
single
soil
to
represent
the
soil
in
the
basin.
In
fact,
soils
can
vary
substantially
across
even
small
areas,
and
this
variation
is
not
reflected
in
these
simulations.

The
index
reservoir
scenario
does
not
consider
tile
drainage.
Areas
that
are
prone
to
substantial
runoff
are
often
tile
drained.
Tile
drainage
contributes
additional
water
and
in
some
cases,
additional
pesticide
loading
to
the
reservoir.
This
may
cause
either
an
increase
or
decrease
in
the
pesticide
concentration
in
the
reservoir.
Tile
drainage
also
causes
the
surface
soil
to
dry
out
faster.
This
will
reduce
runoff
of
the
pesticide
into
the
reservoir.
The
watershed
used
as
the
model
for
the
index
reservoir
(
Shipman
City
Lake)
does
not
have
tile
drainage
in
the
cropped
areas.

Turf
was
used
as
the
site
of
interest
for
trichlorfon.
General
outdoor
uses
were
used
as
the
site
of
interest
for
dichlorvos.
Eight
crops
were
simulated
for
naled.
The
modeling
results
indicate
that
all
these
compounds
have
the
potential
to
contaminate
surface
waters
by
runoff,
for
short
periods
of
time
especially
in
areas
with
large
amounts
of
annual
rainfall.
However,
based
on
its
environmental
fate
characteristics,
naled
will
degrade/
dissipate
rapidly
(
t1/
2
<
1
day),
trichlorfon
and
dichlorvos
will
persist
slightly
longer
(
t1/
2
1.4
and
~
5
days,
respectively).
Mitigation
practices
that
reduce
runoff
could
be
effective
in
reduction
of
these
chemicals
transport
into
surface
waters.
Page
71
of
151
Table
6.2.3a.
Estimated
Drinking
Water
Concentrations
in
Surface
Water
for
Dichlorvos,
Dichlorvos
from
Naled,
and
Dichlorvos
from
Trichlorfon
use
on
Turf
using
Tier
II
PRZM/
EXAMS.

model
EDWCs
(
µ
g/
L)

Dichlorvos1
from
Naled2
from
Trichlorfon3*

Surface
water/
peak
(
90th
percentile
annual
daily
max.
for
acute
exposure
analysis)
3.46
33.0
60
Surface
water/
90th
percentile
annual
mean
for
chronic
exposure
analysis
0.17
1.83
1.56
use(
s)
modeled
4
applications
@
0.20
lb
ai/
acre,
spray
appl.
5
applications
@
1.87
lb
ai/
acre,
spray
appl.
3
applications
@
8.2
lb
ai/
acre,
spray
appl.

PCA
0.87
1
Dichlorvos
from
wide
area
treatment
2
Naled
from
treatment
of
brassica
crops
3
Trichlorfon
turf
treatment
*
Dichlorvos
from
trichlorfon
is
adjusted
for
a
25%
conversion
at
pH
7,
a
pH
typical
of
soils
growing
turf.

The
maximum
amount
of
dichlorvos
formed
from
naled
is
approximately
20%
of
the
applied
naled.
Therefore,
a
conservative
dichlorvos
use
rate
was
selected
as
naled's
use
rate
multiplied
by
0.20.

The
application
rate
used
on
turf
for
trichlorfon
based
on
25
percent
conversion
to
dichlorvos
adjusted
for
differences
in
MW.
A
maximum
of
25%
degradation
of
trichlorfon
to
dichlorvos
was
assumed
because
25%
degradation
was
the
maximum
observed
in
a
hydrolysis
study
at
pH
7,
a
pH
typical
of
soils
used
to
grow
turf.

Table
6.2.3b
shows
the
input
parameters
used
in
PRZM/
EXAMS.
Page
72
of
151
Table
6.2.3b.
Input
parameters
for
Dichlorvos,
Dichlorvos
from
Naled,
and
Dichlorvos
from
Trichlorfon
used
in
PRZM/
EXAMS
models.

Dichlorvos
Information
Chemical
From
Naled
From
Trichlorfon
Dichlorvos
PC
Code
for
parent
chemical
34401
57901
84001
Molecular
weight
(
g/
mole)
220.9
220.9
220.9
Solubility
(
ppm)
10000
10000
10000
Hydrolysis
half­
life,
pH
7
(
days)
5.2
5.2
5.2
Soil
Photolysis
half­
life
(
days)
0.65
0.65
0.65
Aerobic
Soil
Metabolism
half­
life
(
days)
0.42
0.42
0.42
Aerobic
Aquatic
Metabolism
half­
life
(
days)
no
data
no
data
no
data
Soil
Organic
Carbon
Partitioning
(
Koc)(
l/
kg)
37
37
37
Use
Brassica
Turf
Wide
Area
Treatment
Application
Rate
(
lb
a.
i.
/
acr/
yr)
1.87
8.2
0.20
Number
Of
Applications/
year
5
3
4
Interval
between
appl.
(
day)
30
7
30
Application
Method
Spray
Spray
Spray
Page
73
of
151
6.2.4.
Drinking
Water
Risk
Estimates
The
Pesticide
Data
Program
(
PDP)
in
USDA­
Agricultural
Marketing
Service
has
sampled
finished
drinking
water
collected
after
disinfection,
and
just
before
distribution
to
customers,
from
community
water
systems
in
a
few
states
from
2001
through
2004,
and
raw
and
finished
drinking
water
from
community
water
systems
in
a
few
states
in
2004.
In
2001,
PDP
analyzed
214
finished
drinking
water
samples
from
CA
and
NY.
In
2002
and
2003,
PDP
sampled
371
and
699
finished
drinking
water
samples,
respectively,
in
CA,
CO,
KS,
NY,
and
TX.
In
2004,
PDP
sampled
raw
and
finished
water
from
171
community
water
systems
from
MI,
NC,
OH,
OR,
PA,
and
WA.
Dichlorvos
was
one
of
the
analytes.
No
detectable
residues
of
dichlorvos
were
found
at
limits
of
detection
(
LOD)
of
0.4
­
22.5
pptrillion.
Naled
and
trichlorfon
were
not
among
the
analytes
tested,
but
PDP
would
have
detected
dichlorvos
coming
from
naled
and
trichlorfon.

The
PDP
monitoring
of
water
from
community
water
systems
does
not
reflect
the
drinking
water
consumed
by
the
population
for
the
following
reasons:

­
The
PDP
samples
large
community
water
systems
in
a
limited
number
of
states.
The
sampling
sites
are
not
necessarily
in
dichlorvos,
naled,
and
trichlorfon
use
areas,
and
the
data
may
not
be
reflective
of
drinking
water
concentrations
in
areas
of
high
dichlorvos
use.
­
The
community
water
systems
sampled
by
PDP
are
generally
deep
ground
water
or
surface
water
systems.
The
PDP
does
not
sample
individual,
private
wells.
Use
of
the
PDP
data
would
not
be
protective
of
people
whose
drinking
water
source
is
a
private
well.

The
Agency
currently
lacks
sufficient
water­
related
exposure
data
from
monitoring
to
complete
a
quantitative
drinking
water
exposure
analysis
and
risk
assessment
for
dichlorvos.
Therefore,
the
Agency
is
presently
relying
on
computer­
generated
estimated
environmental
concentrations
(
EDWCs).
The
Tier
II
PRZM/
EXAMS
model
turf
scenario
with
the
Index
Reservoir
and
Percent
Crop
Area
adjustment
(
IR­
PCA
PRZM/
EXAMS)
was
used
to
generate
EDWCs
for
surface
water
and
SCI­
GROW
(
an
empirical
model
based
upon
actual
monitoring
data
collected
for
a
number
of
pesticides
that
serve
as
benchmarks)
predicts
EDWCs
in
ground
water.
These
models
take
into
account
the
use
patterns
and
the
environmental
profile
of
a
pesticide,
but
do
not
include
consideration
of
the
impact
that
processing
raw
water
for
distribution
as
drinking
water
would
likely
have
on
the
removal
of
pesticides
from
the
source
water.
The
primary
use
of
these
models
by
the
Agency
at
this
stage
is
to
provide
a
coarse
screen
for
determining
that
pesticides
residues
(
and
metabolites)
in
water
are
not
of
concern.

For
any
given
pesticide,
the
SCI­
GROW
model
generates
a
single
EDWC
for
pesticide
concentration
in
ground
water.
That
EDWC
is
used
in
assessments
of
both
acute
and
chronic
dietary
risk.
It
is
not
unusual
for
the
ground
water
EDWC
to
be
significantly
lower
than
the
surface
water
EDWCs.
The
tier
II
PRZM/
EXAMS
model
provides
long
duration
(
up
to
36­
year)
pesticide
concentrations
in
surface
water
and
is
mainly
used
when
a
refined
EDWC
is
needed.
Page
74
of
151
6.3
Residential
(
Non­
Occupational)
Exposure/
Risk
Pathway
Dichlorvos
is
registered
for
several
residential
uses.
Residential
handlers
may
be
exposed
to
dichlorvos
during
application
of
dichlorvos
in
pressurized
aerosol
spray
cans.
Residential
post
application
exposure
may
occur
after
use
of
the
following
products
containing
dichlorvos:
pressurized
aerosol
spray
can,
resin
pest
strips,
and
pet
flea
collars.
Residential
post
application
exposure
to
dichlorvos
may
also
occur
after
lawn
treatment
with
trichlorfon.
Residential
Exposure
and
Risk
Estimates
are
summarized
in
Table
6.3
below.
Information
sources
and
major
assumptions
for
each
residential
scenario
are
described
below,
with
additional
information
in
the
table
endnotes.
Additional
information
is
available
in
the
referenced
documents
(
Jaquith
D.,
1993b,
Jaquith
D
1998a
through
n,
Jaquith
D.
1999
through
d,
Jaquith,
D,
2000,
and
Jaquith,
D.,
2001
and
2003).
Dichlorvos
exposure
from
the
use
of
Naled
is
covered
by
the
Naled
Risk
Assessment.
Dichlorvos
exposure
from
the
use
of
trichlorfon
is
included
in
this
document.
Although
residential
bystander
exposure
could
result
from
the
use
of
naled,
both
on
field
crops
and
as
a
mosquitocide,
any
exposure
to
dichlorvos
from
the
use
of
naled
would
be
covered
by
the
Naled
Risk
Assessment.

Residential
Scenarios
which
were
evaluated
were
of
acute,
short
term,
or
long
term
duration.
A
BMDL10
of
0.8
mg/
kg/
day
from
a
rat
acute
oral
cholinesterase
study
is
used
for
the
acute
oral,
dermal,
and
inhalation
risk
assessment.
An
11%
dermal
absorption
is
assumed
for
the
dermal
risk
assessment.
The
target
MOE
for
residential
acute
risk
assessments
is
100.

A
LOAEL
of
0.1
mg/
kg/
day
from
a
human
21­
day
oral
study
is
used
for
short
term
incidental
oral,
dermal,
and
inhalation
(
during
application)
risk
assessment.
An
11%
dermal
absorption
is
assumed
for
the
dermal
risk
assessment.
The
target
MOE
for
residential
short
term
risk
assessments
is
30.

A
BMDL10
of
0.07
mg/
m3
from
a
2
year
rat
inhalation
study
is
used
for
the
long
term,
postapplication
inhalation
risk
assessment.
The
target
MOE
for
residential
long
term
inhalation
risk
assessment
is
30.

6.3.1
Home
Uses
6.3.1.1.
Residential
Handler
(
a).
Pressurized
Aerosol
Spray
Can
The
exposure
assessment
for
pressurized
spray
cans
was
derived
from
data
in
the
Pesticide
Handlers
Exposure
Database
(
PHED
V1.1)
and
the
Residential
SOPs
for
aerosol
application.
Residential
use
of
pressurized
aerosol
product
is
based
on
application
of
2
ounces
from
an
aerosol
can
of
0.5
percent
dichlorvos
(
Jaquith
2001;
Jaquith
1998f;
REJV,
2002).
This
is
an
acute
exposure
scenario.

Pressurized
aerosol
products
containing
dichlorvos
do
not
list
any
clothing
requirements;
therefore
the
Agency
is
assuming
that
dichlorvos
is
applied
during
hot
weather
when
an
individual
will
be
wearing
the
least
amount
of
clothing
(
i.
e.,
shorts,
short
sleeve
shirt,
and
shoes).
Using
the
Page
75
of
151
Residential
SOPs,
unit
dermal
exposures
were
220
mg/
lb
ai
handled,
and
1.3
mg
/
lb
ai
handled
for
inhalation
exposure
(
adjusted
for
the
NAFTA
breathing
rate
of
1.0
m3/
hr,
with
an
absorbed
dermal
dose
of
0.00022
mg/
kg/
day.
Respiratory
exposure
was
estimated
to
be
1.2
x
10­
5
mg/
kg/
day.
The
total
exposure
was
2.3
x
10­
4
mg/
kg/
day,
with
an
MOE
of
3500
(
target
MOE
=
100),
which
is
not
of
concern.

6.3.1.2.
Residential
Post­
application
(
a).
Pressurized
Aerosol
Post
application
data
from
a
total
release
fogger
application
were
used
as
a
surrogate
for
the
post
application
exposure
from
pressurized
aerosol
applications.
The
total
release
fogger
treatments
in
the
home
have
been
canceled.
However
the
data
are
still
being
used
to
assess
the
use
of
the
aerosol
spray,
after
adjustment
for
application
rate.

Indoor
residential
post­
application
exposures
for
short
term
exposure
scenarios
were
derived
from
a
single
study
measuring
the
exposures
of
individuals
performing
defined
activity
patterns
(
20
minute
Jazzercise
®
routine)
following
the
activation
of
a
total
release
fogger,
containing
dichlorvos.
This
study
provides
a
conservative
estimate
for
short
term
exposure
scenarios
from
indoor
applications
of
dichlorvos
(
Jaquith
1993b).
The
multi­
phase
study
measured
deposition
on
whole
body
dosimeters
and
(
in
a
separate
phase)
the
urinary
concentrations
of
the
metabolite
dimethyl
phosphate
(
DMP),
a
metabolite
of
dichlorvos.
The
biomonitoring
gave
estimates
of
exposure
of
14
µ
g/
kg.

In
order
to
estimate
the
potential
oral
exposure
from
hand
to
mouth
activity
of
children,
the
amount
of
dichlorvos
measured
on
the
hands
in
the
passive
dosimetry
phase
was
considered
to
be
available
for
ingestion.
The
passive
dosimetry
dose
on
the
hands
had
to
be
added
because
the
Jazzercise
®
routine
does
not
include
hand­
to­
mouth
activity.
The
estimated
exposure
due
to
hand
to
mouth
ingestion,
was
0.61
µ
g/
kg
(
Jaquith
1998k),
or
a
total
exposure
of
15
µ
g/
kg
when
the
potential
oral
component
was
included.
This
is
considered
to
be
a
short­
term
exposure
scenario.
This
study
only
measured
exposures
to
adults;
however,
exposure
to
children
is
expected
to
be
similar
to
that
of
an
adult.

For
post­
application
exposure
and
risk
estimates
from
the
use
of
the
pressurized
aerosol,
it
was
assumed
that
there
would
be
2
oz
of
product
(
containing
0.5%
ai)
used
in
a
1000
sq.
ft.
house
(
from
the
Residential
Exposure
Joint
Venture
(
REJV)
survey
(
REJV,
2002)).
This
amount
was
compared
to
the
amount
that
was
used
for
a
total
release
fogger,
and
the
ratio
used
to
adjust
the
amount
of
the
biomonitoring
study
that
was
conducted.
The
MOE
was
100,
which
is
not
of
concern,
compared
to
the
target
MOE
of
30.
Page
76
of
151
(
b).
Resin
Pest
Strips
Several
sizes
of
resin
pest
strips
are
marketed.
The
full
size,
room
size
strip
is
65
or
80
g,
containing
12.1
or
14.9
g
of
dichlorvos,
used
to
treat
1000
ft
3.
The
full
size
strip
may
no
longer
be
used
in
spaces
occupied
more
than
4
hours
per
day.
Examples
of
spaces
which
may
not
be
occupied
more
than
4
hours
per
day
were
attics,
crawl
spaces,
and
garages.
Other
sizes
of
resin
pest
strips
are
the
large
closet
strip,
16
g,
containing
3.0
g
dichlorvos;
the
small
closet
strip,
10.5
g,
containing
1.8
g
dichlorvos,
and
the
cupboard
strip,
5.25
g,
containing
0.97
g
dichlorvos.

The
dichlorvos
label
for
the
smaller
size
resin
strips
will
have
these
limitations.

"
Only
available
in
the
following
sizes:
16
g
(
0.56
oz),
10.5
g
(
0.37
oz),
and
5.25
g
(
0.9
oz)
pest
strip
sizes"

Household
use.
"
Use
only
in
Closets,
Wardrobes,
and
Cupboards.
Do
not
use
in
areas
of
a
home
where
people
will
be
present
for
an
extended
period
of
time
(
e.
g.,
Living
Room,
Family
Room).
Do
not
use
in
any
rooms
or
closets
of
rooms
where
infants,
children
and
the
sick
or
aged
are
or
will
be
present
for
any
extended
period
of
confinement.
Do
not
use
where
unwrapped
food
is
stored,
or
allow
the
strip
to
come
into
contact
with
food
or
cooking
utensils.
Do
not
allow
children
or
pets
to
play
or
sleep
in
these
areas
when
treatment
is
in
progress."

Storage
Units,
Attics,
Garages,
Sheds,
and
Enclosed
Crawl
Spaces.
"
Do
not
use
in
areas
of
a
home
where
people
will
be
present
for
an
extended
period
of
time.
[
Keep]
out
of
reach
of
children
and
pets,
in
an
open
space
of
an
enclosed
area,
away
from
windows."

The
largest
pest
strip,
100
g,
will
no
longer
be
registered.
The
large
80
g
and
65
g
pest
strips
will
be
separated
into
a
separate
registration,
where
the
label
will
state:

"
Only
available
in
65
g
and
80
g
pest
strip
sizes."

"
DIRECTIONS
FOR
USE"
"
For
use
in
unoccupied
areas,
not
for
use
in
homes
except
garages,
attics,
crawl
spaces,
and
sheds
occupied
for
less
than
4
hours
per
day.
"
Also
for
use
in
the
following
unoccupied
structures,
provided
they
are
unoccupied
for
more
than
4
months
immediately
following
placement
of
a
pest
strip:
vacation
homes,
cabins,
mobile
homes,
boats,
farm
houses,
and
ranch
houses."

Respiratory
exposures
resulting
from
the
use
of
resin
pest
strips
were
estimated
using
a
study
found
in
the
scientific
literature
(
Collins
and
DeVries,
1973).
Fifteen
homes
were
monitored
at
various
time
intervals
for
a
period
of
91
days.
Air
monitoring
was
done
in
one
place
in
each
of
the
homes,
in
the
same
room
with
the
full
sized
resin
pest
strip
(
80
or
100
g
strips).
A
decay
curve
measuring
the
decline
of
airborne
residues
was
derived
for
each
of
these
homes.
The
resulting
equations
were
integrated
over
a
91
day
period
and
an
average
concentration
was
calculated
(
Jaquith
1998a,
1999d,
and
2000).
The
average
air
concentration,
over
this
time
period
was
estimated
to
be
0.015
mg/
m3.
Smaller
sized
resin
strips
placed
in
a
closet
or
cupboard
would
be
expected
to
have
Page
77
of
151
lower
concentrations
by
direct
proportion,
assuming
that
the
residue
of
dichlorvos
in
the
air
would
equilibrate
between
the
closet
or
cupboard
and
the
room.

Margins
of
Exposure
were
calculated
for
the
resin
pest
strips
using
the
90
day
average
air
concentration
in
the
house
(
0.015
mg/
m3)
from
a
65
­
80
g
pest
strip
containing
12.09
­
14.9
g
dichlorvos
in
a
1000
ft3
room
(
Collins,
R.
D.
and
DeVries,
D.
M.
1973),
and
the
BMDL10
from
a
chronic
rat
inhalation
study
of
0.07
mg/
m3,
based
on
RBC
cholinesterase,
and
23
hours
of
exposure.
The
margins
of
exposure
will
vary,
depending
on
the
exposure
time
and
the
size
of
the
pest
strip,
as
shown
in
Table
6.3.1.2.
below.

Table
6.3.1.2.
Exposures/
MOEs
for
dichlorvos
resin
strips,
based
on
size
of
resin
strip
and
time
exposed
BMDL10:
0.07
mg/
m
3
for
RBC
cholinesterase
from
2
year
rat
inhalation
study
Exposure
duration:
23
hours
per
day,
7
days
a
week
90­
day
average
concentrations
of
0.015
mg/
m
3
Target
MOE
=
30
Size
of
Resin
Strip
Full
size
Closet
Closet
Cupboard
g
product
65
16
10.5
5.25
g
dichlorvos
12.09
3.0
1.95
0.975
Hours
exposed
per
day
Margin
of
Exposure
(
MOE)

1
110
470
660
1300
2
54
240
330
660
4
27
120
170
330
6
18
78
110
220
8
13
60
83
170
10
11
35
67
130
12
9
40
55
110
14
8
34
48
95
16
7
30
42
83
18
6
26
37
74
20
5
24
33
67
22
5
21
30
60
24
4
20
28
55
The
MOEs
in
table
6.3.1.2
are
calculated
as
follows.

MOE
=
0.07
mg/
m3
x
23
hr/
day
x
65
g
dichlorvos
in
full
size
strip
0.015
mg/
m3
Hr
exposed
per
day
g
dichlorvos
in
product
The
dichlorvos
label
has
been
changed
to
allow
use
of
resin
strips
in
areas
occupied
up
to
4
hours
per
day
(
garages,
attics,
 )
.
Although
this
use
would
be
allowed
by
the
label,
there
is
no
expectation
that
individuals
will
actually
be
exposed
at
this
level
routinely.
Page
78
of
151
AMVAC
has
proposed
a
study
to
measure
air
concentrations
from
use
of
the
smaller
resin
strips
in
closets
and
cupboards.
The
study
has
been
required
by
California,
but
not
EPA.
A
protocol
was
submitted
by
the
registrant
to
EPA
and
reviewed
(
Jaquith,
2003a).
The
Agency's
comments
were
provided
to
AMVAC.
Some
suggestions
were
made
to
improve
the
study,
including
diagrams
of
the
houses,
placement
of
the
air
monitors,
and
monitoring
of
fabric
in
the
closets
with
a
closet
sized
strip.
To
date,
the
study
has
not
been
submitted
to
EPA.

(
c).
Pet
Flea
Collars
A
flea
collar
is
placed
on
the
pet's
neck
to
protect
the
pet
from
fleas
over
the
life
of
the
collar.
It
is
expected
that
the
flea
collar
will
be
replaced
when
it
is
no
longer
efficacious,
which
is
assumed
to
be
120
days.

In
this
assessment,
inhalation
exposure
was
estimated
for
the
flea
collars,
considering
them
to
be
a
mobile
resin
strip,
because
the
formulation
is
similar
to
the
resin
strip
formulation.
A
dog
collar,
containing
2.2
g
dichlorvos,
would
contain
(
2.2/
12.1)
or
18
%
of
the
amount
of
dichlorvos
contained
in
a
full
sized
resin
strip.
The
air
concentration
in
the
room
with
the
pet
is
estimated
to
average
0.0027
mg/
m3
for
8
hours
per
day.

In
addition,
dermal
exposure
and
children's
hand­
to­
mouth
exposure
assessments
were
done,
using
a
draft
ExpoSAC
policy.
The
calculations
for
the
assessment
are
shown
in
the
footnote
for
table
6.3.
The
dermal
exposure
was
estimated
to
contribute
0.0011
mg/
kg/
day
and
hand­
to­
mouth
exposure
was
estimated
to
be
0.0001
mg/
kg/
day.

Combining
the
dermal
and
hand­
to­
mouth
exposure
results
in
an
exposure
estimate
of
0.0012
mg/
kg/
day,
and
an
MOE
of
83.
The
inhalation
MOE
is
74,
and
the
total
MOE
is
39,
which
is
greater
than
the
target
MOE
of
30,
and
not
of
concern.

(
d).
Lawns
and
Turf
­
Post­
Application
Dichlorvos
from
the
use
of
Naled.
Naled
is
used
as
a
mosquitocide,
and
may
result
in
residues
on
home
lawns.
This
use
was
considered
in
the
Naled
Risk
Assessment.

Dichlorvos
from
the
use
of
Trichlorfon.
Post
application
exposure
to
dichlorvos
from
the
use
of
trichlorfon
has
been
assessed.
(
Leighton,
T.,
2000).
This
is
a
short­
term
exposure
scenario.
Trichlorfon
is
applied
to
home
lawns
at
8.2
lb
ai/
acre
as
a
granular
formulation,
which
is
watered
in
with
0.25"
water.
The
assessment
for
dichlorvos
from
trichlorfon
use
utilized
an
environmental
fate
model
to
predict
residues
of
a
parent
and
a
metabolite,
based
on
the
trichlorfon
half­
life
from
a
trichlorfon
turf
transferable
residue
study
(
TTR)
and
the
dichlorvos
half­
lives
from
a
turf
transferable
residue
study
for
dichlorvos.
The
turf
assessment
has
been
modified
to
assume
25%
degradation
of
trichlorfon
to
dichlorvos,
based
on
the
25%
maximum
conversion
in
a
hydrolysis
study
of
trichlorfon
at
pH
7,
a
pH
typical
of
home
lawns.
Trichlorfon
degrades
less
at
lower
pH's
and
up
to
50%
at
pH
8.4
(
Jones,
R.
D.,
2006).
Page
79
of
151
Hand­
to­
mouth
residues
were
estimated
using
the
Residential
SOPs.
Trichlorfon
was
applied
at
8.1
lb
ai/
A
(
registered
rate
is
8.2
lb
ai/
a).
The
initial
TTR
of
trichlorfon
was
0.0829
µ
g/
cm2.
Exposure
from
hand­
to­
mouth
activity
for
toddlers
was
added
to
arrive
at
total
estimated
exposure.
The
maximum
amount
of
dichlorvos
was
estimated
to
occur
11
hours
after
application.
(
Leighton,
2000).
Toddler
dermal
plus
hand
to
mouth
MOEs
ranged
from
430
to
710,
compared
to
a
target
MOE
of
30.

Inhalation
exposure
from
this
scenario
could
not
be
assessed,
because
air
concentrations
in
the
breathing
zone
of
toddlers
were
not
provided
in
the
trichlorfon
study.
For
comparison
purposes,
inhalation
estimates
from
the
equivalent
dichlorvos
dermal
exposure
is
provided
in
the
table.
These
inhalation
exposure
estimates
are
expected
to
overestimate
inhalation
exposure
because
of
differences
in
the
application
method
between
dichlorvos
and
trichlorfon,
and
because
the
maximum
dichlorvos
formed
was
predicted
to
occur
11
hours
after
application.
"
Wetting
in"
the
trichlorfon
granules
is
expected
to
reduce
the
amount
of
dichlorvos
available
for
volatilization
(
Jones,
R.
D.,
2006).

A
trichlorfon
TTR
study
with
analyses
for
dichlorvos
in
the
turf
and
in
the
toddler
breathing
zone
above
the
turf
(
18")
is
being
requested
to
confirm
these
exposure
estimates.
The
study
must
be
conducted
at
an
appropriate
pH
(
approx.
7).
A
field
dissipation
study
may
be
substituted,
provided
it
meets
these
requirements.

6.3.2
Recreational
Uses
The
dichlorvos
and
trichlorfon
turf
uses
could
also
be
recreational
uses.
They
are
addressed
above
in
Section
6.3.1
Home
uses.
The
same
exposures
would
be
expected
for
recreational
uses
as
home
lawn
uses.

6.3.3
Other
(
Spray
Drift,
etc.)

Spray
drift
is
always
a
potential
source
of
exposure
to
residents
nearby
to
spraying
operations.
This
is
particularly
the
case
with
aerial
application,
but,
to
a
lesser
extent,
could
also
be
a
potential
source
of
exposure
from
ground
application
methods.
However,
there
are
no
field
crop
applications
employed
for
dichlorvos.
The
Agency
has
been
working
with
the
Spray
Drift
Task
Force,
EPA
Regional
Offices
and
State
Lead
Agencies
for
pesticide
regulation
and
other
parties
to
develop
the
best
spray
drift
management
practices.
On
a
chemical
by
chemical
basis,
the
Agency
is
now
requiring
interim
mitigation
measures
for
aerial
applications
that
must
be
placed
on
product
labels/
labeling.
The
Agency
has
completed
its
evaluation
of
the
new
data
base
submitted
by
the
Spray
Drift
Task
Force,
a
membership
of
U.
S.
pesticide
registrants,
and
is
developing
a
policy
on
how
to
appropriately
apply
the
data
and
the
AgDRIFT
computer
model
to
its
risk
assessments
for
pesticides
applied
by
air,
orchard
airblast
and
ground
hydraulic
methods.
After
the
policy
is
in
place,
the
Agency
may
impose
further
refinements
in
spray
drift
management
practices
to
reduce
off­
target
drift
with
specific
products
with
significant
risks
associated
with
drift.
Page
80
of
151
Table
6.3.
Summary
of
Residential
Exposure
and
Risk
Estimates
for
Dichlorvos
Current
Exposure
(
mg/
kg/
day)
Current
MOE
MOE
USES
NOTES
EXPOSURE
PATTERN
1
Dermal
Inhalation
Total
Dermal
Inhalation
Total
RESIDENTIAL
EXPOSURE
All
Target
MOEs
for
all
Residential
Scenarios
are
30,
except
for
acute
dermal
and
handler
exposure
scenarios,
where
the
target
MOE
is
100.

RESIDENTIAL
HANDLER
2
(
a)
Pressurized
aerosol
spray
can
3
Acute
0.00022
0.000012
0.00023
3600
67000
3500
RESIDENTIAL
POST­
APPLICATION
(
a)
Pressurized
aerosol
(
toddler)

Same
rate
as
fogger
Adjusted
rate
4
Short­
term
Dose
is
0.90
µ
g/
kg/
day
based
on
urinary
dimethyl
phosphate
+

incidental
oral
of
0.038
µ
g/
kg/
day
0.00098
100
(
b)
Resin
pest
strips
Full
size
strip
65
g
(
4
hr
exposure)

Smaller
strips
(
14
hr
exposure)

Closet
strip
16
g
Small
Closet
strip
10.5g
Cupboard
strip
5.25g
5
Long­
term,
Inhalation
N/
A
N/
A
N/
A
N/
A
0.015
mg/
m
3
.

0.0048
mg/
m
3
.

0.0024
mg/
m
3
0.0012
mg/
m
3
.
27
34
48
95
27
34
48
95
(
c)
Pet
flea
collars
toddler(
includes
hand­
to­
mouth)
6
Long­
term
0.0012
0.000949
mg/
m
3
83
74
39
(
d)
Lawns,
Trichlorfon
use
8.1
lb
ai/
A
Post­
application
Although
inhalation
exposure
is
not
assessed,
rough
estimates
were
made
by
comparison
with
dichlorvos
turf
study,
which
we
expect
to
result
in
an
over­
estimate
of
the
exposure
&
risk.

Toddler
­
high
end
0.00023
not
assessed
430
(
100)

Toddler
­
low
end
7
Short­
term
(
adding
incidental
oral
of
0.0004
mg/
kg/
day
0.00014
not
assessed
710
(
150)

NOTES:
The
following
notes
define
the
assumptions
used
in
calculating
the
margins
of
exposure.

Risk
is
expressed
as
a
Margin
of
Exposure
(
MOE)

MOE
=
NOAEL
,
where
both
the
NOAEL
and
the
Exposure
are
expressed
in
common
units
Exposure
Page
81
of
151
1.
Doses
and
toxicological
endpoints
for
assessment
of
short
term
dermal,
incidental
oral
and
inhalation
(
applicator)
residential
risks
are
based
on
an
oral
LOAEL
of
0.1
mg/
kg/
day
from
a
human
21­
day
repeated
dose
study.
A
dermal
absorption
factor
of
11%
was
used
in
assessing
risks
from
dermal
exposure.
The
applicator
is
assumed
to
weigh
70
kg.
The
target
MOE
for
these
scenarios
is
30
(
10x
for
intraspecies
variability,
3x
for
use
of
the
LOAEL).

Doses
and
toxicological
endpoints
for
assessing
risks
from
long­
term
inhalation
of
dichlorvos
vapors
are
based
on
an
inhalation
BMDL10
of
0.07
mg/
m
3
from
a
2
year
rat
inhalation
study.
The
target
MOE
for
this
scenario
is
30
(
10x
for
intraspecies
variability,
3x
for
interspecies
extrapolation).

Acute
Dermal
and
Inhalation
endpoints
are
based
on
the
0.8
mg/
kg/
day
BMDL10
from
a
rat
acute
oral
cholinesterase
study,
with
an
11%
dermal
absorption
factor
for
the
dermal
exposure.
The
target
MOEs
are
100
(
10x
for
interspecies
extrapolation,
and
10x
for
intraspecies
variability)

2.
Residential
handler
assumptions.
An
average
resident
applicator
weighs
70
kg
and
has
a
respiratory
volume
of
1.0
m
3
/
hour
(
NAFTA
value
for
moderate
activity).
Assume
applicator
wears
short
pants,
short
sleeves,
and
no
gloves.

3.
Pressurized
aerosol
spray
­
residential
handler.
Residential
use
of
pressurized
aerosol
product
is
based
on
application
of
2
ounces
of
0.5
percent
dichlorvos
pressurized
aerosol
(
0.00063
lb
ai).
Pressurized
aerosol
products
containing
dichlorvos
do
not
have
any
clothing
requirements;
therefore
EPA
is
assuming
that
dichlorvos
is
applied
during
hot
weather
when
an
individual
will
be
wearing
only
shorts,
short
sleeve
shirt,
and
shoes.
From
the
Residential
SOPs
unit
dermal
exposures
are
220
mg/
lb
ai
handled,
and
1.3
mg
/
lb
ai
handled
for
inhalation
exposure
(
after
correction
for
the
NAFTA
breathing
rate).
The
risk
assessment
is
based
on
application
by
a
70
kg
resident
applicator.
(
Jaquith,
2001).

Dermal
exposure
=
220
mg/
lb
ai
handled
x
0.005
x
2
oz/
16
oz/
lb
x
0.11
(
dermal
absorption
factor)
÷
70
kg
=
0.00022
mg/
kg/
day
Inhalation
Exposure
=
1.3
mg/
lb
ai
x
0.000625
lb
ai
÷
70
kg
=
1.2
E­
5
mg/
kg/
day
Total
exposure
=
0.00022
+
0.000012
=
0.00023
mg/
kg/
day
Total
MOE
=
0.8/
0.00023
=
3500
4.
Pressurized
Aerosol
­
Post
application.
The
assessment
is
based
on
biomonitoring
data
(
urinary
excretion
of
DMP
from
exposure
to
dichlorvos)
from
the
use
of
the
Total
Release
Fogger
and
represents
the
total
dose
to
the
individual
from
all
routes.
To
account
for
children's
hand­
to­
mouth
exposure,
an
estimate
of
incidental
oral
exposure
was
obtained
by
assuming
that
all
material
on
hands
(
from
passive
dosimetry
data)
is
available
for
ingestion.
(
Jaquith,
1998k)
The
oral
exposure
from
passive
dosimetry
is
added
to
the
dermal
exposure
from
biomonitoring.
(
Jaquith,

1993b)
Children,
performing
the
same
activities
as
adults
were
considered
to
have
the
same
exposure
as
an
adult
on
a
mg
per
kg
basis.

Total
Exposure
(
µ
g/
kg/
day)
=
Biomonitoring
Exposure
(
µ
g/
kg/
day)
+
Hand­
to­
mouth
Exposure
(
µ
g/
kg)

=
15
µ
g/
kg/
day
+
0.61
µ
g/
kg
=
16
µ
g/
kg
In
the
biomonitoring
study,
an
average
of
1.7
mg
dichlorvos
was
released
into
a
room
of
16.8
m
2
A
lower
application
rate
is
used
for
the
pressurized
aerosol,
compared
to
the
total
release
fogger.
The
risk
assessment
is
done
by
using
the
results
of
the
biomonitoring
study,
and
the
ratio
of
the
application
rate
expected
to
be
used
for
the
pressurized
aerosol
to
the
rate
that
was
used
in
the
biomonitoring
study.

The
2
oz
application
rate
for
the
pressurized
aerosol
in
a
typical
1000
sq
ft
house
is
from
the
REJV
data.

Application
rate
for
aerosol
=
2
oz
x
0.5%
=
6.2
x
10
­
7
lb/
sq.
ft.

16
oz
x
1000
ft
2
Application
rate
in
biomonitoring
study
=
0.77
g
dichlorvos
=
9.9
x
10
­
6
lb/
sq.
ft.

16.8
m
2
x
(
3.2
ft
/
m)
2
x
454
g/
lb
Ratio
of
application
rates
=
6.2
x
10
­
7
lb/
sq.
ft.
=
0.063
9.9
x
10
­
6
lb/
sq.
ft
Total
Exposure
incl.
Hand­
to­
mouth
=
15.6
µ
g/
kg/
day
x
0.063
=
0.98
µ
g/
kg/
day
Page
82
of
151
MOE
=
0.1
mg/
kg/
day
=
100
(
Target
=
30)

0.00098
mg/
kg/
day
5.
Resin
Strips
MOEs
were
based
on
the
average
air
concentration
(
0.015
mg/
m
3
)
in
15
houses
over
a
90­
day
period
(
Collins
and
DeVries
1973,
in
Jaquith
1998h)
and
the
BMDL10
of
0.07
mg/
m
3
from
2
year
rat
inhalation
study.
Exposure
estimates
are
adjusted
to
14
hours
in
the
house.
Exposure
estimates
for
smaller
resin
strips
assume
air
concentrations
are
proportional
to
the
weight
of
the
ai
in
the
strip.
The
target
MOE
for
inhalation
exposure
is
100.

MOE
(
full
sized
strips)
=
0.07/
0.015
x
23
hr
exposure/
14
hr
=
8
Table
6.3.1.2
shows
Exposures
and
MOEs
for
different
exposure
times
to
different
sizes
of
resin
pest
strips.

6.
Inhalation
assessment
assumes
that
a
flea
collar
is
like
a
mobile
resin
strip,
and
the
resident
spends
8
hours
per
day
in
the
room
with
the
pet.
The
air
concentration
is
obtained
by
proportion
based
on
the
ratio
of
ai
in
the
collar
to
the
ai
in
the
full
sized
resin
strip.
MOEs
for
many
different
times
of
exposure
are
found
in
Table
6.3.1.2.

A
full
size
resin
strip
of
65
g
(
12.09
g
ai)
results
in
an
air
concentration
of
0.015
mg/
m
3
.
The
point
of
departure
(
POD)
is
0.07
mg/
m
3
from
23
hours
of
exposure.
The
inhalation
exposure
is
0.015
mg/
m
3
x
2.2
g
dichlorvos
x
8
hr
=
0.000949
mg/
m
3
12.09
g
ai
23
hr
The
MOE
is
0.07
mg/
m
3
/
0.000949
mg/
m
3
=
74
Dermal
exposure
is
estimated
as
follows
from
draft
ExpoSAC
policy
The
amount
of
dichlorvos
available
per
dog
per
day
is
2.2
g
in
the
collar,
divided
by
the
120
days
that
the
collar
is
effective,
2.2
g
x
1000
mg/
g/
120
days
=
18.3
mg/
dog/
day.

The
draft
ExpoSAC
policy
assumes
20%
of
the
residue
is
transferrable,
but
a
carbaryl
study
(
MRID
45792201)
showed
2.6%
transferrable.

18.3
mg/
dog/
day
x
.026
transferrable
=
0.00008
mg/
cm
2
transferrable
residue
5986
cm
2
surface
area
on
a
30
lb
dog
A
child
is
assumed
to
hug
a
dog
and
contact
1875
cm
2
of
the
dog's
fur.
The
dermal
absorption
is
11%.
A
toddler
is
assumed
to
weigh
15
kg.

0.00008
mg/
cm
2
transferrable
residue
x
1875
cm
2
x
.11
dermal
absorption
factor
=
0.0011
mg/
kg/
day
15
kg
child
For
the
hand­
to­
mouth
component,
1
event
per
hour
is
assumed.
The
surface
area
of
a
child's
hand
which
goes
into
the
mouth
is
20
cm
2
.
The
child
is
assumed
to
play
with
the
dog
for
2
hours
per
day.
The
saliva
extraction
factor
is
50%.

0.00008
mg/
cm
2
x1
event/
hr
x
20
cm
2
x
0.5
x
2
hr/
day
=
0.0001
mg/
kg/
day
15
kg
child
Combining
the
dermal
and
hand­
to­
mouth
exposure
results
in
an
exposure
estimate
of
0.0012
mg/
kg/
day,
and
an
MOE
of
83
7.
The
calculations
for
incidental
oral
and
dermal
exposure
to
children
playing
on
turf
have
been
updated
to
be
consistent
with
the
revised
Residential
SOPs.
Activities
on
the
lawn
are
assumed
to
start
1
hour
or
more
after
spraying,
and
last
2
hours
per
day.

The
assessment
for
dichlorvos
from
trichlorfon
use
relied
on
the
dichlorvos
half­
lives
from
the
same
TTR
study
for
dichlorvos,
trichlorfon
total
transferable
residues
(
TTR)
residues
from
a
trichlorfon
DFR
study,
and
the
Residential
SOPs.
TTRs
of
dichlorvos
were
estimated
using
the
calculated
half­
lives
of
trichlorfon
and
dichlorvos
(
0.53
hours­
3.7
hours).
The
calculations
were
done
using
a
spreadsheet­
based
model
developed
by
EFED
to
estimate
the
decay
rate
of
a
chemical
and
its
degradate
applied
to
short
grass
for
single
or
multiple
applications.
The
initial
trichlorfon
concentration
was
derived
from
a
Trichlorfon
TTR
study.
A
first
order
decay
assumption
is
used
to
determine
the
concentration
at
each
day
after
initial
application
based
on
the
concentration
resulting
from
the
initial
and
additional
applications.
Exposure
from
hand­
to­
mouth
activity
for
toddlers
was
added
to
arrive
at
total
estimated
exposure.
(
Leighton,
2000).
The
formulas
are
presented
below.
(
a)
is
the
exponential
form,
and
(
b)
is
the
log
transformed
versions.
Page
83
of
151
(
a)
CpT
=
Cpie
­
k1T
(
b)
In
(
CpT/
Cpi)
=
k1T
For
the
degradate
Cd,
=
(
k1Cpi)
e
­
k1T
­
e
­
k2T
)/(
k2k1)

Where:

CpT
=
parent
concentration
at
time
T
=
day
T.

Cpi
=
parent
concentration
at
time
T
=
day
zero
(
0.0138
bcg/
cn
from
trichiorton
HR
study;
MRID
45067201).

k1
=
parent
degradation
rate
constant
determined
from
the
trichlorfon
TTR
study
using
half
life
data
of
0.93
and
2.5
days
(
MRID
45067201).

k2
=
DDVP
degradation
rate
constant
determined
from
the
DDVP
TTR
studies
using
a
half
life
of
0.156
days
(
MRIDs
44591901,
44610501,
and
44794901).

The
high
end
exposure
(
daily
dermal
dose)
for
dichlorvos
from
trichlorfon,
adjusting
for
25%
conversion
to
dichlorvos
was
0.00019
mg/
kg/
day.
Hand­
to­
mouth
exposure
was
0.00004
mg/
kg/
day,
totaling
0.00023
mg/
kg/
day.

This
results
in
an
MOE
of
BMDL10
=
0.8
mg/
kg/
day
=
3500
Exposure
0.00023
mg/
kg/
day
The
inhalation
MOEs
presented
in
the
table
are
based
on
the
ratio
of
the
dermal
exposure
to
dichlorvos
after
treatment
of
dichlorvos
to
the
dermal
exposure
to
dichlorvos
after
treatment
with
trichlorfon.
These
estimates
are
expected
to
overestimate
the
exposure
and
risk.
Page
84
of
151
7.0
Aggregate
Risk
Assessments
and
Risk
Characterization
The
Food
Quality
Protection
Act
amendments
to
the
Federal
Food,
Drug,
and
Cosmetic
Act
(
FFDCA,
Section
408(
b)(
2)(
A)(
ii))
require
that
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
are
reliable
information."
Aggregate
exposure
is
the
total
exposure
to
a
single
chemical
(
or
its
residues)
that
may
occur
from
all
sources.
Typically
these
are
dietary
(
i.
e.,
food,
and
drinking
water),
residential
and
other
non­
occupational
sources,
and
from
all
known
or
plausible
exposure
routes
(
oral,
dermal
and
inhalation).

In
an
aggregate
assessment,
estimated
exposures
from
relevant
sources
are
added
together
and
compared
to
quantitative
estimates
of
hazard
(
e.
g.,
a
NOAEL,
LOAEL,
BMDL,
or
PAD),
or
the
risks
themselves
can
be
aggregated.
When
aggregating
estimated
exposures
and
risks
from
various
sources,
HED
considers
both
the
route
and
duration
of
exposure.
Aggregate
risk
assessments
are
typically
conducted
for
acute
(
1
day),
short­
term
(
1­
30
days),
intermediate­
term
(
30
days
to
6
months),
and
chronic
(
6
months
to
lifetime)
exposure.

Dichlorvos
residues
may
be
present
in
water
and/
or
food
as
a
result
of
use
of
three
pesticides:
dichlorvos
(
DDVP),
naled,
and
trichlorfon.
Dichlorvos
is
a
degradate
of
naled
and
trichlorfon.
The
Environmental
Fate
and
Effects
Division
(
EFED)
evaluated
the
potential
for
dichlorvos
to
contaminate
water
from
these
sources.
The
environmental
fate
properties
of
dichlorvos,
naled,
and
trichlorfon
are
an
indicator
of
the
potential
of
these
compounds
to
migrate
to
ground
or
surface
water.
EFED
has
limited
monitoring
data
on
the
concentrations
of
dichlorvos,
naled,
or
trichlorfon
in
groundwater.
Validated
monitoring
data
for
dichlorvos,
naled,
and
trichlorfon
are
available
for
the
states
of
California
and
Hawaii
from
the
Pesticides
in
Groundwater
Database,
and
from
a
few
other
states
in
the
PDP.
These
data
indicated
that
neither
naled,
dichlorvos,
nor
trichlorfon,
have
been
detected
in
groundwater
nor
drinking
water;
however,
these
data
were
not
targeted
to
the
pesticide
use
area.
OPP
does
not
have
sufficient
ground
or
surface
water
monitoring
data
on
the
concentrations
of
dichlorvos,
naled,
or
trichlorfon
at
the
present
time.
Therefore,
the
Tier
I
screening
model
SCI­
GROW
was
used
to
estimate
ground
water
concentrations
for
naled,
trichlorfon
and
dichlorvos.
The
Tier
II
PRZM/
EXAMS
model
was
used
to
estimate
drinking
water
concentrations
from
surface
water.

A
probabilistic
acute
dietary
exposure
assessment
was
conducted
without
the
water
contribution.
The
chronic
dietary
exposure
assessment
was
also
conducted
without
the
water
contribution.
Sufficient
water
modeling
data
were
available
to
use
for
probabilistic
assessment
if
needed.

For
residential
exposure
and
risk
assessment,
deterministic
exposure
assessments
were
done.
Exposure
estimates
for
a
number
of
occupational
and
residential
scenarios
were
derived
from
limited
data
from
the
scientific
literature,
textbooks,
and
knowledge
of
cultural
practices.
Other
estimates,
particularly
in
the
residential
environment,
were
derived
from
chemical
specific
monitoring
data,
including
biomonitoring,
in
combination
with
models
and
literature
studies.
Page
85
of
151
The
route
of
exposure
which
results
in
the
greatest
exposure
to
residents
depends
on
the
use
pattern.
For
resident
applicators
and
reentry
after
use
of
an
aerosol
spray,
the
dermal
route
of
exposure
results
in
the
highest
estimated
risk.
For
the
pest
strip
and
reentry
onto
lawns,
the
inhalation
risk
is
estimated
to
be
the
highest.
In
general,
the
residential
risks
are
estimated
to
be
much
higher
than
food
and
water
combined.

Drinking
Water
Levels
of
Comparison
(
DWLOCs).
For
dichlorvos
(
and
most
pesticide
active
ingredients),
water
monitoring
data
are
considered
inadequate
to
determine
surface
and
ground
water
drinking
water
exposure
estimates,
so
model
estimates
have
been
used
to
estimate
residues
in
drinking
water
(
Estimated
Drinking
Water
Concentrations,
or
EDWCs,
see
Table
6.2.3a
and
6.2.3b).
In
order
to
determine
if
aggregate
risks
are
of
concern,
HED
then
calculates
drinking
water
levels
of
comparison,
or
DWLOCs.
The
DWLOC
is
the
maximum
amount
of
a
pesticide
in
drinking
water
that
would
be
acceptable
in
light
of
combined
exposure
from
food
and
residential
pathways.
The
calculated
DWLOCs
are
then
compared
to
the
EDWCs
provided
by
EFED;
if
model­
derived
EDWCs
exceed
the
DWLOCs
for
surface
or
ground
water,
there
may
be
a
concern
for
exposure
to
residues
in
drinking
water.

HED
has
calculated
drinking
water
levels
of
comparison
(
DWLOCs)
associated
with
acute
and
chronic
exposure
to
dichlorvos
in
drinking
water.
These
DWLOCs
are
compared
with
the
estimated
drinking
water
concentrations
(
EDWCs)
of
dichlorvos
in
water.

7.1
Acute
Aggregate
Risk
The
acute
aggregate
risk
estimate
to
dichlorvos
includes
exposures
from
food
and
drinking
water.
Although
there
are
several
acute
residential
exposure
scenarios,
these
will
be
included
in
the
short
term
aggregate
risk
assessment
because
it
is
highly
unlikely
that
high
exposure
from
food,
water,
and
residential
use
will
co­
occur.
For
the
highly
refined
acute
probabilistic
dietary
exposure
analysis,
PDP
and
FDA
monitoring
data
and
FDA
TDS
data
were
used
to
the
greatest
extent
possible,
along
with
field
trial
data,
cooking
and
processing
factors,
and
degradation
studies
to
assess
dietary
exposures.

The
acute
DWLOC
for
dichlorvos
includes
aggregate
exposure
from
food
and
water
only.
The
DWLOCacute
was
calculated
for
the
general
population,
All
Infants,
Children
(
1­
6
years)
who
are
the
most
highly
exposed
population
subgroup,
and
for
females
(
13­
50
years).
Acute
water
exposures
and
DWLOC
calculations
are
summarized
in
Table
7.2.4.1.
below.

DWLOCacute
(
µ
g/
L)
=
acute
drinking
water
exposure
(
mg/
kg/
day)
x
body
weight
(
kg)
Water
consumption
(
L/
day)
x
(
10­
3
mg/
µ
g)

where
body
weight
is
70
kg
for
adults,
60
kg
for
females
(
13­
50)
and
15
kg
for
children
and
water
consumption
is
2
L
per
day
for
adults
and
1
L
per
day
for
children.
acute
water
exposure
=
aPAD
­
acute
food
exposure
where
aPAD
is
0.008
mg/
kg/
day.
Page
86
of
151
Table
7.1.
Summary
of
DWLOCacute
Calculations
for
Dichlorvos.

DEEM
Population
Subgroup
Acute
Dietary
Exposure
to
Dichlorvos
at
99.9th
%
tile,
mg/
kg/
day
Acute
aPAD,
mg/
kg/
day
Allowable
Water
Exposure,
mg/
kg/
day
DWLOCacute,
µ
g/
L
Maximum
EDWCacute
µ
g/
L
US
Population
0.00014
0.008
280
60
All
Infants
0.00031
0.008
120
60
Children
(
1­
6)
0.00033
0.008
120
60
Females
(
13­
50)
0.000085
0.008
240
60
For
acute
drinking
water
exposure,
the
modeled
groundwater
concentrations
of
0.0002
to
0.015
µ
g/
L
for
dichlorvos
resulting
from
the
use
of
dichlorvos,
naled,
and
trichlorfon
are
not
of
risk
concern,
when
compared
to
the
DWLOCACUTE,
shown
above
in
Table
7.1.
There
is
no
risk
concern
from
the
estimated
drinking
water
concentration
of
dichlorvos
in
surface
water,
resulting
from
the
use
of
dichlorvos,
of
3.46
µ
g/
L,
from
naled,
of
33.0
µ
g/
L,
nor
from
trichlorfon,
of
60
µ
g/
L.

7.2
Short­
Term
Aggregate
Risk
The
short­
term
aggregate
risk
estimate
includes
chronic
dietary
(
food
and
water)
from
dichlorvos
uses,
and
acute
and
short­
term
non­
occupational
exposures
(
i.
e.,
residential/
recreational
uses).

There
are
two
short­
term
residential
exposure
scenarios
which
could
be
aggregated
with
food
and
water:
the
application
of
the
aerosol
spray
and
the
resulting
post­
application
exposure
,
and
postapplication
exposure
to
dichlorvos
from
turf
treatment
with
trichlorfon.
Since
the
exposures
from
the
aerosol
spray
and
the
exposures
from
treated
lawns
are
so
short­
lived
(
a
week
or
less),
it
is
extremely
unlikely
that
an
individual
would
be
exposed
concurrently.
Accordingly,
two
separate
aggregate
scenarios
are
presented.
It
should
be
noted
that
the
contribution
of
food
and
water
to
the
short­
term
aggregate
risk
is
considered
to
be
negligible
occupying
less
than
one
percent
of
the
risk
cup.
Consequently,
the
short­
term
aggregate
risk
is
mainly
a
result
of
the
residential
exposures
presented
in
each
of
the
scenarios.

The
first
scenario
includes
the
residential
use
of
the
aerosol
spray
can.
Exposure
from
the
application
of
the
aerosol
spray
is
considered
to
be
negligible
(
i.
e.,
an
MOE
of
3500
was
calculated
vs.
a
target
MOE
of
100)
with
the
majority
of
the
exposure
occurring
post­
application.
The
MOE
calculated
from
post­
application
exposures
was
100
vs.
the
target
MOE
of
30.
When
these
residential
exposures
are
combined
(
aggregated)
with
the
exposures
from
food
and
water
and
compared
to
the
short­
term
endpoint,
our
risk
level
of
concern
is
not
exceeded.
Page
87
of
151
Table
7.2.
Short­
Term
Aggregate
Risk
and
DWLOC
Calculations
Short­
Term
Scenario
(
post
application
from
spraying
with
an
aerosol
can)

Target
MOE
=
30
Short­
term
LOAEL
=
0.1
mg/
kg/
day
Population
Target
Aggregate
MOE
MOE
Food1
MOE
residen­
tial2
Aggregate
MOE
(
food
and
residential)
3
MOE
Water4
Allowable
water
exposure5
(
mg/
kg/
day)
Ground
Water
EDWC6
(
ppb)
Surface
Water
EDWC6
(
ppb)
DWLOC7
(
µ
g/
L)

Adult
Female
30
330000
100
100
43
0.0023
0.01
1.83
69
Child
30
77000
100
100
43
0.0023
0.01
1.83
34
1
MOE
food
=
[(
short
or
intermediate­
term
oral
NOAEL)/(
chronic
dietary
exposure)]
=
0.1mg/
kg/
day/
0.0000003
mg/
kg/
day
for
adult
females
=
330000
=
0.1
mg/
kg/
day/
0.0000013
mg/
kg/
day
=
77000
2
MOE
residential
=
[(
short
or
intermediate­
term
oral
NOAEL)/(
residential
exposure)]

3
Aggregate
MOE
(
food
and
residential)
=
1
÷
[
[(
1
÷
MOE
food)
+
(
1
÷
MOE
oral)
+
(
1
÷
MOE
dermal)
+
(
1
÷
MOE
inhalation)]]

4
Water
MOE
=
1
÷
[[(
1
÷
Target
Aggregate
MOE)
­
(
1
÷
Aggregate
MOE
(
food
and
residential)]]

5
Allowable
water
exposure
=
Short
or
Intermediate
Term
Oral
NOAEL
÷
MOE
water
6
The
crop
producing
the
highest
level
was
used.

7
DWLOC(
µ
g/
L)
=
[
allowable
water
exposure
(
mg/
kg/
day)
x
body
weight
(
kg)]

[
water
consumption
(
L)
x
10­
3
mg/
µ
g]

Where
body
weight
=
15
kg
for
a
child,
and
60
kg
for
a
woman.

The
other
scenario
involves
the
post­
application
exposure
to
dichlorvos
from
the
use
of
trichlorfon
on
turf.
As
discussed
previously,

data
from
trichlorfon
are
not
available
to
calculate
exposures
resulting
from
this
use
and
the
Agency
has
used
available
data
and
modeling
from
dichlorvos
to
estimate
these
exposures.
The
MOEs
calculated
did
not
exceed
our
level
of
concern
(
i.
e.,
were
greater
than
our
target
MOE
of
30)
and
the
Agency
expects
that,
given
the
negligible
contribution
from
food
and
water,
short­
term
aggregate
risks
do
not
exceed
our
level
of
concern.
Data
for
the
use
of
trichlorfon
on
turf
will
be
required
to
confirm
these
conclusions.
Page
88
of
151
7.3
Intermediate­
Term
Aggregate
Risk
The
intermediate­
term
aggregate
risk
estimate
includes
chronic
dietary
(
food
and
water)
from
dichlorvos
uses,
and
intermediate­
term
non­
occupational
exposures
(
i.
e.,
residential/
recreational
uses).
There
are
no
residential/
recreational
uses
with
an
intermediate­
term
exposure
scenario.
Therefore,
intermediate­
term
aggregate
risks
were
not
evaluated.

7.4
Long­
Term
Aggregate
Risk
The
long­
term
aggregate
risk
estimate
for
dichlorvos
combines
chronic
exposures
from
food,
drinking
water,
and
long­
term
residential
exposures.
There
are
two
long­
term
residential
scenarios:
resin
strips
and
pet
(
flea)
collars.
While
it
is
possible
that
an
individual
could
be
exposed
concurrently
to
dichlorvos
from
the
use
of
resin
strips,
have
a
pet
that
wears
a
dichlorvos
collar
and
consume
food
and
drink
water
with
dichlorvos
residues,
the
probability
of
these
simultaneous
exposures
is
fairly
low,
especially
considering
the
market
share
of
these
residential
uses.
Consequently,
two
separate
scenarios
are
discussed
for
long­
term
aggregate
risk.

The
contribution
of
dichlorvos
in
food
occupies
less
than
one
percent
of
the
risk
cup
for
longterm
exposure.
When
potential
exposure
to
water
is
added,
approximately
23
percent
of
the
risk
cup
is
occupied
leaving
77
percent
(
equating
to
an
MOE
of
39)
for
any
additional
exposures
resulting
from
residential
use.

The
first
scenario
considers
the
pet
collar.
As
discussed
previously
in
this
document,
the
Agency
has
made
a
number
of
conservative
assumptions
in
deriving
a
risk
estimate
for
this
use.
Included
in
these
assumptions
is
that
the
pet
collar
acts
as
a
miniature
resin
strip
which
results
in
inhalation
exposure
proportional
to
that
of
larger
resin
strips
and
that
the
pet
is
in
the
same
room
as
an
individual
for
8
hours
a
day.
Additionally,
exposures
were
calculated
based
on
dermal
contact
(
from
hugging
and
petting
activities)
as
well
as
incidental
oral
(
hand
to
mouth)
exposures
exhibited
by
children.
The
inhalation
MOE
is
calculated
to
be
74
and
the
dermal
and
incidental
oral
MOE
of
83
for
a
comined
MOE
of
39
vs.
our
target
MOE
of
30.
Therefore,
the
long­
term
aggregrate
risk
does
not
exceed
our
level
of
concern
given
that
this
conservative
estimate
from
the
pet
collar
does
not
exceed
the
amount
left
in
the
risk
cup
after
considering
food
and
water.

The
second
scenario
considers
the
largest
resin
strip.
The
registrant
recently
voluntarily
amended
its
registration
to
limit
where
these
strips
can
be
used.
No
use
will
be
permitted
in
living
areas
and
the
labeling
warns
of
exposure
to
the
strips
for
more
than
4
hours.
The
Agency
believes
that
given
the
location
of
where
these
strips
may
be
used
(
e.
g.,
attics,
crawl
spaces,
garages,
etc),
exposure
times
will
be
much
less
than
4
hours
a
day
and/
or
that
daily
exposure
(
repeated
exposure)
may
not
be
likely
depending
on
the
site
of
application
(
e.
g.,
crawl
spaces).
Consequently,
considering
the
room
available
in
the
risk
cup
after
consideration
of
food
and
water
and
that
exposures
are
not
expected
either
daily
or
for
significant
periods
of
time,
our
risk
of
concern
is
not
exceeded
from
this
long­
term
exposure
scenario.
Page
89
of
151
7.5
Aggregate
Cancer
Risk
No
aggregate
cancer
risk
assessment
is
needed.
Dichlorvos
shows
"
suggestive"
evidence
of
carcinogenicity
under
the
1999
Draft
Agency
Cancer
Guidelines.
No
quantitation
is
required.
No
aggregate
cancer
risk
assessment
is
required.

8.0
Cumulative
Risk
Characterization/
Assessment
Section
408(
b)(
2)(
D)(
v)
of
the
Federal
Food,
Drug,
and
Cosmetic
Act
(
FFDCA),
as
amended
by
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.

Dichlorvos
is
a
member
of
the
organophosphate
(
OP)
class
of
pesticides.
Other
members
of
this
class
of
pesticides
are
numerous
and
include
azinphos
methyl,
chlorpyrifos,
chlorpyrifos­
methyl,
diazinon,
dichlorvos,
dicrotophos,
dimethoate,
disulfoton,
methamidophos,
methidathion,
monocrotophos,
naled,
oxydemeton­
methyl,
phorate,
phosmet,
pirimiphos­
methyl,
and
trichlorfon
to
name
a
few.
EPA
considers
organophosphates
to
express
toxicity
through
a
common
biochemical
interaction
with
cholinesterase
which
may
lead
to
a
myriad
of
cholinergic
effects
and,
consequently
the
organophosphate
pesticides
should
be
considered
as
a
group
when
performing
cumulative
risk
assessments.
HED
published
the
final
guidance
that
it
now
uses
for
identifying
substances
that
have
a
common
mechanism
of
toxicity
(
FR
64(
24)
5796­
5799,
February
5,
1999)
"
Proposed
Guidance
of
Cumulative
Risk
Assessment
for
Chemicals
that
have
a
Common
Mechanism
of
Toxicity"
was
made
available
for
public
comment
in
the
Federal
Register
(
65
FR
40644,
June
30,
2000
.
The
Agency
presented
this
approach
to
the
FIFRA/
FQPA
Science
Advisory
Panel
in
late
September,
2000.
The
SAP
reviewed
revised
methods
used
to
conduct
a
preliminary
cumulative
risk
assessment
for
organophosphate
pesticides
in
2002
(
US
EPA,
2002),
found
at
http://
www.
epa.
gov/
scipoly/
sap/
2002/
index.
htm.

The
Agency
has
completed
a
cumulative
risk
assessment
for
OPs,
(
US
EPA,
2001)
and
a
revised
cumulative
risk
assessment
for
OPs,
(
US
EPA,
2002a)
which
can
be
found
on
the
Agency's
web
site
http://
www.
epa.
gov/
pesticides/
cumulative/
rra­
op/.
It
assesses
the
cumulative
effects
of
exposure
to
multiple
OPs,
including
dichlorvos.

Dichlorvos
is
closely
related
to
naled
and
trichlorfon,
which
are
members
of
the
organophosphate
class
of
pesticides.
Naled
and
trichlorfon
both
metabolize
or
degrade
to
dichlorvos
in
food,
water,
or
the
environment.
Therefore,
FQPA
requires
OPP
to
estimate
aggregate
risk
from
consumption
of
Page
90
of
151
food
and
water,
containing
dichlorvos
derived
from
naled
and
trichlorfon
and
from
residential
exposure
to
dichlorvos
from
the
use
of
those
pesticides.
The
current
assessment
addressed
only
the
risks
posed
by
dichlorvos,
resulting
from
the
uses
of
dichlorvos,
naled,
and
trichlorfon.

9.0
Occupational
Exposure/
Risk
Pathway
Risk
is
expressed
as
a
Margin
of
Exposure
(
MOE)

MOE
=
NOAEL
Exposure
where
both
the
NOAEL
and
the
Exposure
are
expressed
in
the
same
units
(
mg/
kg/
day
for
dermal
or
inhalation
exposure
during
application
or
mg/
m3
for
exposure
to
dichlorvos
vapors).
Dermal
exposures
include
a
dermal
absorption
factor
of
11%,
because
the
exposure
is
compared
to
an
oral
NOAEL.
The
target
MOE
for
occupational
scenarios
varies
from
30
to
100.
(
See
Table
4.4).

The
risk
assessment
has
been
changed
from
previous
versions
to
use
the
North
American
Free
Trade
Agreement
(
NAFTA)
recommended
breathing
rate
of
1.0
m3
/
hr
rather
than
the
rate
recommended
in
the
guidelines
or
the
default
breathing
rate
used
in
PHED.
This
change
increases
the
inhalation
MOEs,
and
therefore
decreases
the
estimated
risk
to
occupational
and
residential
handlers.
The
risk
assessment
uses
the
recommended
body
weight
of
70
kg
for
the
acute,
short
term,
and
intermediate
term
risk
assessments.

AMVAC
has
requested
voluntary
cancellation
of
the
following
uses.
Mushroom
house,
greenhouse,
and
warehouse
hand
held
fogger
Lawn,
Turf,
and
Ornamental
uses
Total
release
fogger
Crack
and
Crevice
uses
The
following
label
changes
will
be
made:
A
Restricted
Entry
Interval
(
REI)
of
18
hours
for
mushroom
houses,
and
12
hours
for
greenhouse
uses.

Toxicological
Doses
and
Endpoints
for
Occupational
Exposure
Assessment
are
presented
in
Table
9.0.
Occupational
exposure
and
risk
estimates
for
applicators
are
presented
in
Table
9.1
below.
Occupational
post­
application
exposure
and
risk
estimates
are
presented
in
Table
9.2
below.
Page
91
of
151
Table
9.0.
Summary
of
Toxicological
Doses
and
Endpoints
for
Dichlorvos
for
Use
in
Occupational
Human
Health
Risk
Assessments
Exposure
Scenario
Point
of
Departure
Uncertainty
Factors
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
Acute
Dermal
BMDL10
=
0.8
mg/
kg/
day
dermal
absorption=
11%
UFA
=
10x
UFH
=
10x
Occupational
LOC
MOE
=
100
Rat
acute
oral
cholinesterase
studies
­
RBC
and
Brain
ChE
depression.
NOAEL
=
1
mg/
kg/
day,
LOAEL
=
5
mg/
kg/
day,
BMD
=
1.6
mg/
kg/
day
for
brain
ChE
depression
(
F)

Short­,
Intermediateand
Long­
Term
Dermal
Oral
study
LOAEL=
0.1
mg/
kg/
day
dermal
bsorption=
11%
UFH
=
10x
UFL
=
3x
Occupational
LOC
MOE
=
30
Human
21­
day
oral
study
LOAEL
=
0.1
mg/
kg/
day
based
on
RBC
ChE
depression
Acute
Inhalation
(
1
day)
Oral
study
BMDL10
=
0.8
mg/
kg/
day
(
inhalation
absorption
rate
=
100%)
Air
concentration
Equivalent
=
0.8
mg/
m
3
*
UFA
=
10x
UFH
=
10x
or
3x**
Occupational
LOC
MOE
=
100/
30**
Rat
acute
oral
cholinesterase
studies
­
RBC
and
Brain
ChE
depression.
NOAEL
=
1
mg/
kg/
day,
LOAEL
=
5
mg/
kg/
day,
BMD
=
1.6
mg/
kg/
day
for
brain
ChE
depression
(
F)

Short­
and
Intermediate­
term
Inhalation
of
vapors
Oral
study
LOAEL=
0.1
mg/
kg/
day
UF=
30
Concentration
equivalent=
0.35
mg/
m
3
*
UFH
=
10x
UFL
=
3x
Occupational
LOC
MOE
=
30
Human
21­
day
oral
study
LOAEL
=
0.1
mg/
kg/
day
based
on
RBC
ChE
depression
Short­
and
Intermediate­
Term
Inhalation
during
application
LOAEL=
0.1
mg/
kg/
day
UFH
=
10x
UFL
=
3x
Occupational
LOC
MOE
=
30
Human
21­
day
oral
study
LOAEL
=
0.1
mg/
kg/
day
based
on
RBC
ChE
depression
Long­
Term
Inhalation
of
vapors
BMDL10
=
0.07
mg/
m
3
UFA
=
10x
UFH
=
3x**
Occupational
LOC
=
30
2­
year
Rat
Inhalation
BMD
=
0.15
mg/
m
3
based
on
RBC
ChE
depression
(
F)

Cancer
(
oral,
dermal,
inhalation)
"
suggestive"
evidence
of
carcinogenicity
not
quantifiable
under
the
1999
Draft
Agency
Cancer
Guidelines
Point
of
Departure
(
POD)
=
A
data
point
or
an
estimated
point
that
is
derived
from
observed
dose­
response
data
and
used
to
mark
the
beginning
of
extrapolation
to
determine
risk
associated
with
lower
environmentally
relevant
human
exposures.
NOAEL
=
no
observed
adverse
effect
level.
LOAEL
=
lowest
observed
adverse
effect
level.
UF
=
uncertainty
factor.
UFA
=
extrapolation
from
animal
to
human
(
intraspecies).
UFH
=
potential
variation
in
sensitivity
among
members
of
the
human
population
(
interspecies).
UFL
=
use
of
a
LOAEL
to
extrapolate
a
NOAEL.
UFS
=
use
of
a
short­
term
study
for
long­
term
risk
assessment.
UFDB
=
to
account
for
the
absence
of
key
date
(
i.
e.,
lack
of
a
critical
study).
MOE
=
margin
of
exposure.
LOC
=
level
of
concern.
N/
A
=
Not
Applicable
*
Calculation
of
concentration
equivalent
BMDL10
and
LOAEL
Acute
Inhalation
BMDL10
0.8
mg/
kg/
day
x
0.35
kg
/
0.34
m
3
/
day
=
0.8
mg/
m
3
Short­
and
Intermediate­
term
inhalation
of
vapors
LOAEL
0.1
mg/
kg/
day
x
70
kg
/
20
m
3
/
day
=
0.35
mg/
m
3
**
Since
the
NOAEL
is
expressed
in
concentration
units
(
RfC
methodology),
the
interspecies
extrapolation
factor
is
3x
(
for
the
acute
and
long
term
inhalation
scenarios),
for
a
total
UF
of
30
for
acute
inhalation
and
long
term
inhalation.
Page
92
of
151
9.0.1.
Mushroom
House
(
a).
Application
Application
of
dichlorvos
to
mushroom
houses
may
be
made
by
coarse
spray
and
paint­
on
applications.
Foggers
would
be
permitted
if
the
applicator
is
outside
the
mushroom
house.
The
exposures
for
coarse
spray
applications
were
derived
from
ORETF
data.
The
Outdoor
Residential
Exposure
Task
Force
(
ORETF)
has
recently
completed
several
surrogate
mixer/
loader/
applicator
studies
addressing
lawn
care
operators
(
LCOs).
(
Bangs,
2001;
Jaquith,
2001).
The
hose­
end
sprayer
scenario
from
the
ORETF
studies
will
be
used
to
estimate
exposures
to
applicators
in
mushroom
houses.
Estimates
of
the
surface
areas
that
would
be
painted
or
sprayed
during
dichlorvos
application
were
derived
from
mushroom
culture
textbooks
and
are
considered
to
be
conservative
(
Jaquith
1998d
and
n).
This
application
scenario
is
considered
to
be
intermediate
term
(
several
months)
because
a
single
individual
may
treat
different
mushroom
houses
on
different
days
due
to
the
cyclic
nature
of
mushroom
culture.

Coarse
Spray
and
Paint­
on
Applications.
For
the
coarse
spray,
data
from
the
ORETF
lawn
care
study
were
used;
protective
clothing
varied
with
the
application
method,
and
included
long
pants,
long
sleeved
shirt
and
gloves,
or
coveralls
plus
long
pants,
long
sleeved
shirt
and
gloves.
The
label
does
not
specify
protective
clothing
needed.
Dermal
and
inhalation
exposure
and
total
exposure
resulting
in
an
MOE
of
46
is
not
considered
to
be
of
concern,
compared
to
the
target
MOE
of
30.
If
an
additional
layer
of
protective
clothing
were
added,
the
absorbed
dermal
dose
would
be
cut
approximately
in
half,
and
the
MOE
of
88
would
be
adequate.

(
b).
Post­
application
For
reentry
exposure,
it
was
assumed
that
a
worker
reenters
a
ventilated
mushroom
house
12
or
24
hours
after
treatment
and
is
exposed
for
8
hours.
This
is
a
short
term
exposure
because
workers
may
be
exposed
multiple
times
on
subsequent
days.
The
MOE
at
a
12
hour
REI
of
23
is
less
than
the
target
MOE
of
30,
and
is
of
concern.
The
MOE
at
a
24
hour
REI
of
58
is
greater
than
the
target
MOE
of
30,
and
is
not
of
concern.
AMVAC
has
submitted
an
amendment,
changing
the
label
REI
to
18
hours.

9.0.2.
Greenhouse
(
a).
Application
There
are
currently
no
end
use
product
labels
with
directions
for
use
for
greenhouses.
However,
the
technical
label
for
Dichlorvos
allows
use
of
up
to
2.0
g/
1000
cu.
ft.
Previously,
smoke
generators
were
registered,
and
were
considered
to
result
in
negligible
applicator
exposure
since
the
applicator
vacates
the
premises
immediately
upon
activation
of
the
smoke
generator.
This
application
scenario
is
considered
to
be
short
term
because
treatment
would
not
be
expected
to
occur
in
a
given
greenhouse
more
than
once
a
week.
The
baseline
MOE
is
46,
which
is
not
of
concern.
Page
93
of
151
(
b).
Post­
application
The
dermal
exposure
for
reentry
into
greenhouses
following
the
use
of
dichlorvos
was
obtained
using
data
from
a
greenhouse
culture
textbook,
data
on
turf
transferable
residues
from
a
chlorpyrifos/
dichlorvos
study
(
Goh,
K.
S.,
et.
al.
1986),
and
a
standard
transfer
coefficient
of
2500
cm2/
hr,
from
ExpoSAC
Policy
003.
Inhalation
exposure
estimates
were
modeled
assuming
the
initial
concentration
at
the
maximum
rate,
assuming
first
order
kinetics
and
an
air
exchange
rate
from
a
textbook
(
Mastalerz,
1977).
This
is
considered
to
be
a
short­
term
exposure
scenario
(
Jaquith,
1998d).

The
total
daily
dermal
exposure
that
would
occur
after
a
2
hour
REI
is
estimated
to
be
1.2
µ
g/
kg/
day.
The
dichlorvos
concentrations
available
for
inhalation
exposure
were
modeled
(
Jaquith,
1998d),
and
concentrations
depended
on
the
ventilation
used.
The
estimated
respiratory
component
of
exposure
would
be
0.00035
mg/
m3.
The
resulting
MOE
with
a
2
hour
REI
of
78
is
not
of
concern,
compared
to
the
target
MOE
of
30.
At
a
12
hr
REI,
the
total
MOE
is
>
650
and
is
not
of
concern,
compared
to
the
target
MOE
of
30.

9.0.3.
Domestic
Animal
Premises
(
food
and
nonfood)
and
Direct
Animal
Sprays,
Feedlots,
Manure
Treatment,
Garbage
Dumps,
and
Baits
(
a).
Application
Dairy
barn
application
and
direct
application
to
dairy
cattle
were
used
as
the
reference
facility
for
these
exposure
assessments
(
Jaquith
1998l).
There
are
no
data
addressing
the
use
of
dichlorvos
in
other
types
of
animal
facilities.
Worker
exposure
from
direct
application
to
animals
is
based
on
dairy
cattle
treatment.
Although
permitted
on
product
labels,
the
Agency
does
not
believe
that
direct
application
to
livestock
animals
with
a
handheld
sprayer
is
used.
Rather,
some
type
of
automated
equipment
is
used
to
apply
dichlorvos
directly
to
animals.
Space
and
premise
treatments
also
help
control
insects
on
animals.
Since
several
registered
products
provide
guidance
on
use
with
a
handheld
sprayer,
the
exposure
and
risk
are
estimated
here
for
that
application
method,
which
is
expected
to
result
in
a
much
higher
exposure
than
automated
methods.
While
some
labels
indicate
that
daily
application
(
probably
for
direct
application
to
cattle)
is
allowable,
the
use
assessment
indicates
that
the
material
is
applied
at
2
week
intervals
(
Dow,
M.,
1985).
This
assessment
assumes
daily
applications
over
several
months,
and
is
therefore
considered
to
be
an
intermediate
term
scenario.

Cattle.
Exposure
assessments
for
direct
application
to
dairy
cattle
using
hand­
held
sprayers
as
a
surface
spray
or
space
spray
were
conducted
using
PHED
V1.1.
Applicators
were
assumed
to
be
wearing
long
sleeved
shirt,
long
pants,
and
gloves.
Gloves
are
not
currently
required
on
the
label.
Absorbed
dermal
doses
were
estimated
to
range
from
0.009
to
0.22
µ
g/
kg/
day
and
respiratory
doses
from
0.008
to
0.039
µ
g/
kg/
day,
depending
on
application
equipment.
These
total
MOEs
would
range
from
440
to
59000,
and
are
not
considered
to
be
of
concern.
Page
94
of
151
Poultry.
Applicator
exposure
data
for
cattle
cannot
be
extrapolated
to
poultry,
because
of
the
different
application
method
and
less
frequent
applications.
Individual
animals
are
less
likely
to
be
treated
directly
and
the
equipment
is
more
likely
to
be
automated.
As
a
result,
exposure
from
applying
dichlorvos
to
poultry
is
expected
to
be
much
lower
than
for
cattle.
Therefore,
no
separate
assessment
has
been
done.

Domestic
Animal
Premises.
Barn
sizes
were
obtained
from
the
dichlorvos
Qualitative
Use
Assessment
(
QUA)
(
Dow,
M.,
1985).
Assuming
that
a
worker
wears
long
sleeve
shirt,
long
trousers,
shoes
and
impervious
gloves
at
a
minimum,
risks
from
dichlorvos
application
to
domestic
animal
premises
are
lower
than
the
risks
from
direct
application
to
cattle,
with
total
MOEs
from
440
to
5900,
and
do
not
exceed
the
Agency's
level
of
concern.
Gloves
are
not
currently
required
on
all
dichlorvos
labels.

Feedlots
include
stockyards,
corrals,
holding
pens
and
other
areas
where
large
groups
of
animals
are
contained.
EPA
assumes
that
some
type
of
power
sprayer
capable
of
treating
a
large
number
of
animals
in
a
short
time
is
probably
used.
A
short
application
time
period
in
an
outdoor
or
partially
enclosed
area
would
minimize
exposure
to
less
than
that
of
dairy
applications.

Manure
Treatment.
The
application
equipment
used
for
manure
applications
may
be
similar
to
those
used
in
a
dairy
barn;
however,
the
application
time
would
probably
be
less
and
the
treated
area
would
be
well
ventilated
­
either
outdoors
or
in
a
partially
enclosed
area.
The
MOE
for
applicators
is
expected
to
be
greater
than
the
target
MOE
for
manure
use.

(
b).
Reentry
There
are
no
data
addressing
potential
reentry
into
animal
facilities.
Re­
entry
exposure
to
animal
premises
would
not
be
expected
to
exceed
reentry
exposure
for
greenhouses,
and
would
be
expected
to
be
considerably
less,
since
animal
premises
are
usually
outdoors
or
well
ventilated,
where
minimal
dermal
contact
is
expected.

9.0.4.
Food
Manufacturing
Plant,
Warehouse
Treatment
(
a).
Application
Dichlorvos
can
be
applied
to
warehouses
with
wall­
mounted
automatic
foggers.
Exposure
to
mixer/
loaders
through
automatic
application
is
expected
to
be
negligible;
however,
there
would
still
be
reentry
exposure.

(
b).
Post­
application
In
estimating
reentry
exposure,
EPA
assumed
24
hours
elapsed
before
reentry
is
allowed,
the
label
REI;
and
that
workers
in
food
manufacturing
plants
spend
8
hours
per
day
in
the
treated
area,
and
2
hours
per
day
in
warehouses.
Absorbed
dermal
exposure
was
measured
for
the
hands
only,
which
is
likely
to
be
the
greatest
route
of
dermal
exposure,
and
represents
an
average
of
the
total
exposure
measured
for
three
work
stations,
and
was
negligible
compared
to
the
inhalation
exposure.
Page
95
of
151
This
exposure
scenario
was
considered
to
be
acute
due
to
rapid
dissipation
of
dichlorvos
(
1
day)
and
sporadic
use.
(
Jaquith,
D.,
2000a;
Jaquith,
D,
1993c).

The
dermal
exposure
estimate
is
0.00022
mg/
kg/
day
for
food
manufacturing
plants.
The
mean
air
concentration
of
dichlorvos
in
a
food
manufacturing
plant
is
estimated
to
be
0.053
mg/
m3
,
24
hours
after
application,
which
results
in
an
exposure
of
0.006
mg/
kg/
day.
The
estimated
air
concentration
in
a
warehouse
after
a
24
hour
REI
is
0.074
mg/
m3
.
This
is
an
acute
exposure
scenario
with
an
MOE
of
130
(
target
MOE
is
100)
for
food
manufacturing
plants,
and
650
for
warehouses,
neither
of
which
is
of
concern.

9.0.5.
Railcars
and
Trucks
(
a).
Application
Dichlorvos
can
be
applied
to
railcars
and
trucks
as
a
fog
or
as
a
surface
spray.
This
is
a
short
term
exposure
scenario.
One
to
ten
railcars
or
trucks
could
be
treated
in
a
single
day.
Application
with
a
surface
spray
would
have
MOEs
of
320,
compared
to
a
target
MOE
of
30,
which
would
not
be
of
concern.

(
b).
Post­
application
In
estimating
reentry
exposure,
EPA
assumed
6
hours
elapsed
before
reentry
is
allowed,
and
that
workers
could
spend
1
hour
per
truck
or
railcar
and
could
load
4
railcars
or
trucks
per
day.
Workers
loading
rail
cars
or
trucks
would
not
be
expected
to
have
dermal
exposure
to
dichlorvos.
The
air
concentration
was
estimated
using
initial
air
concentrations
calculated
from
the
application
rate,
and
assuming
ventilation
similar
to
a
food
processing
establishment.
This
exposure
scenario
was
considered
to
be
short
term
due
to
rapid
dissipation
of
dichlorvos.
(
Jaquith,
D.,
2005).
The
air
concentration
6
hours
after
treatment
is
estimated
to
be
0.018
mg/
m3.
The
MOE
would
be
94,
which
is
not
of
concern,
compared
to
the
target
MOE
of
30.
There
is
considerable
uncertainty
about
the
air
exchange
rate.
Under
the
conditions
described,
the
air
exchange
rate
could
be
as
low
as
1/
3
per
hour.

9.0.6.
Insect
Traps
Exposure
is
believed
to
be
negligible
since
the
pesticide
is
in
the
form
of
an
impregnated
strip
in
a
sealed
package,
which
is
opened
and
the
applicator
leaves,
and
the
traps
are
placed
in
outdoor
areas
(
such
as
forests)
where
there
is
no
human
exposure.

9.0.7.
Occupational
Uses
of
Resin
Strips
The
dichlorvos
label
contains
the
following
use
patterns
and
restrictions.

Garbage
Cans,
Trash
Dumpsters,
Catch
Basins,
Utility
Enclosures.
Keep
lid
on
can
and
dumpster
closed.
Page
96
of
151
Animal
Buildings,
Milk
Rooms.
Do
not
contaminate
food,
water
or
foodstuffs.
Do
not
contaminate
milk
or
milking
equipment.

Agricultural
Commodities:
Bulk
Storage
of
raw
grains,
corn,
soybeans,
cocoa
beans,
and
peanuts.
No
restrictions.

Reptile
Houses
and
Terrariums.
Make
sure
that
the
reptiles
can
not
touch
or
contact
the
strip.

Exposure
to
dichlorvos
from
these
use
patterns
is
expected
to
be
small
compared
to
the
use
of
resin
strips
in
homes,
provided
that
workers
are
in
the
facilities
treated
for
short
periods
of
time.
Refer
to
table
6.3
for
exposure
and
risk
information.
Page
97
of
151
Table
9.1
Occupational
Applicator
Exposure
and
Risk
Estimates
1
Scenario
Endnote
Duration
#
ai/
day
Dermal
unit
exposure
Inhalation
unit
exposure
Dermal
Exposure
Inhalation
Exposure
Total
Exposure
Dermal
MOE
Inhalation
MOE
Total
MOE
Mushroom
house
&
Greenhouse
2
­
ORETF
Hose
End
Sprayer
Intermediate
term
2.6
0.52
0.001
0.00212
0.00004
0.0022
47
2700
46
­
ORETF
Hose
End
Sprayer
+

coveralls
Intermediate
term
2.6
0.27
0.001
0.00110
0.00004
0.00061
91
2700
88
Direct
animal
treatment
3
­
Hand
Held
Sprayer
Intermediate
term
0.092
0.17
0.017
0.000025
0.000023
0.000047
4100
4400
2100
­
Backpack
Sprayer
(
471)
Intermediate
term
0.092
2.6
0.017
0.000376
0.000023
0.000399
270
4400
250
­
Backpack
Sprayer
(
416)
Intermediate
term
0.092
0.27
0.017
0.000039
0.000023
0.000062
2600
4400
1600
­
Portable
Sprayer
on
Cart
Intermediate
term
0.092
0.69
0.052
0.000100
0.000068
0.000168
1000
1500
600
Dairy
barns
­
space
spray
4
­
Hand
Held
Sprayer
Short
term
0.033
0.17
0.017
0.000009
0.000008
0.000017
11000
12000
5900
­
Backpack
Sprayer
(
471)
Short
term
0.033
2.6
0.017
0.000135
0.000008
0.000143
740
12000
700
­
Backpack
Sprayer
(
416)
Short
term
0.033
0.27
0.017
0.000014
0.000008
0.000022
7100
12000
4500
­
Portable
Sprayer
on
Cart
Short
term
0.033
0.69
0.052
0.000036
0.000025
0.000060
2800
4100
1700
Dairy
barns
­
surface
spray
­
Hand
Held
Sprayer
Short
term
0.053
0.17
0.017
0.000014
0.000013
0.000027
7100
7600
3700
­
Backpack
Sprayer
(
471)
Short
term
0.053
2.6
0.017
0.000217
0.000013
0.000230
460
7600
440
­
Backpack
Sprayer
(
416)
Short
term
0.053
0.27
0.017
0.000022
0.000013
0.000036
4400
7600
2800
­
Portable
Sprayer
on
Cart
Short
term
0.053
0.69
0.052
0.000057
0.000039
0.000097
1700
2500
1000
Rail
cars
and
trucks
5
­
Surface
Spray
Short
term
0.28
0.67
0.0032
0.00030
0.000013
0.00031
330
7700
320
Feedlots
6
Short
term
Manure
7
Short
term
Garbage
Dumps
8
Short
term
No
data;
not
expected
to
exceed
dairy
barn
exposure
NOTES:
The
parameters
and
assumptions
used
in
calculating
the
margins
of
exposure
are
found
in
the
endnotes
below
,
Risk
is
expressed
as
a
Margin
of
Exposure
(
MOE)

MOE
=
NOAEL
,
where
both
the
NOAEL
and
the
Exposure
are
expressed
in
mg/
kg/
day
or
mg/
m
3
Exposure
Page
98
of
151
The
target
MOE
for
occupational
exposure
scenarios
is
30.

1.
Occupational
Exposure
assumptions.
An
average
worker
weighs
70
kg
and
has
a
respiratory
volume
of
1.0
m
3
/
hour
(
NAFTA
Value).
At
a
minimum,
the
following
protective
clothing
was
used
in
the
exposure
scenarios:
gloves,
long­
sleeve
shirt,
long
pants
2.
Mushroom
Houses
and
Greenhouses
Mushroom
Houses
­
coarse
spray.
A
typical
mushroom
operation
is
believed
to
consist
of
10
houses,
each
with
a
volume
of
30000
ft
3
(
850
m
3
).
The
label
does
not
specify
protective
clothing
needed.
If
an
individual
treats
all
10
houses
at
a
rate
of
2
grams
per
1000
ft
3
the
amount
handled
in
a
day
would
be:

Amount
handled
(
lb
ai/
day)
=
30000
ft
3
/
house
x
10
houses/
day
x
2
g/
1000
ft
3
=
1.3
lb
ai/
day
454
g/
lb
ai
Workers
are
assumed
to
be
wearing
a
single
layer
of
clothing
and
gloves.
A
second
assessment
was
done
for
applicators
wearing
coveralls.
Data
from
the
ORETF
lawn
care
study
were
used
(
liquid
formulation,
hose
end
sprayer).

AMVAC
does
not
have
a
coarse
spray
registered.
There
was
a
canceled
product,
EPA
Reg.
No.
72­
375
that
had
use
directions
for
the
coarse
spray
or
paint­
on
application
to
mushroom
houses.
The
use
specified
0.25
lb
of
a
0.5%
solution
to
treat
100
sq
ft.
If
we
assume
that
a
typical
mushroom
house
is
6000
sq
ft,
the
amount
handled
per
day
would
be
about1.5
lb
ai/
day.
Thus,
the
mushroom/
greenhouse
assessment
presented
in
this
table
estimates
a
somewhat
higher
exposure
than
what
would
be
expected.

Greenhouse
­
The
average
greenhouse
has
an
estimated
volume
was
85,000
ft
3.
A
typical
operation
was
assumed
to
consist
of
10
greenhouses
which
could
be
treated
in
a
single
day.
Treatment
was
estimated
to
be
3.75
minutes
per
house
or
26
minutes
(
0.44
hrs)
per
day.
Dichlorvos
is
applied
at
the
rate
of
1.4
grams
of
active
ingredient
per
1,000
ft
3
.
Workers
were
assumed
to
be
a
single
layer
of
clothing
and
gloves.
Treatment
would
not
be
expected
to
occur
in
a
given
greenhouse
more
than
once
a
week,
resulting
in
a
short
term
exposure
scenario.
Workers
are
assumed
to
weigh
70
kg.
The
unit
exposures
were
14
mg/
lb
ai
handled
for
dermal
exposure,
and
0.19
mg/
lb
ai
handled
for
inhalation
exposure.

The
typical
application
rate
for
dichlorvos
in
a
greenhouse
is
1.4
g
per
1000
ft
3
.
The
amount
handled
per
greenhouse
would
be:

Amount
handled
(
lb
ai/
greenhouse)
=
1.4
g
ai/
1000
ft
3
x
85000
ft
3
/
greenhouse
=
120
g
ai/
greenhouse
=
0.26
lb
ai/
greenhouse
The
amount
handled
per
day
would
be:

Amount
handled
(
lb
ai/
day)
=
0.26
lb
ai/
greenhouse
x
10
greenhouses/
day
=
2.6
lb
ai/
day
3.
Domestic
Food/
Non­
food
Animals
(
non­
poultry).
Worker
exposure
from
direct
application
to
animals
is
based
on
dairy
cattle
treatment.
A
one
percent
solution
of
dichlorvos
is
applied
with
a
handheld
sprayer.
An
average
herd
of
dairy
cattle
consists
of
65
head,
each
requiring
24
seconds
to
spray,
two
times
per
day
during
treatment.
Fly
control
is
required
from
May
to
October
with
application
expected
to
be
occurring
weekly
rather
than
2
x
per
day
during
this
time
(
26
times
per
year).

Although
permitted
on
product
labels,
EPA
does
not
believe
that
direct
application
with
a
handheld
sprayer
is
used.
Rather,
some
type
of
automated
equipment
is
used
to
apply
dichlorvos
directly
to
animals.
Space
and
premise
treatments
also
help
control
insects
on
animals.
Since
several
registered
products
provide
guidance
on
use
with
a
handheld
sprayer,
the
exposure
and
risk
are
estimated
here
for
that
application
method,
which
is
expected
to
result
in
a
much
higher
exposure
than
automated
methods.
The
exposure
assessment
for
direct
application
to
dairy
cattle
using
a
handheld
sprayer
was
conducted
using
PHED
V1.1.
Applicators
were
assumed
to
wear
long
sleeve
shirts,
long
pants,
and
gloves.
Page
99
of
151
Domestic
Food/
Non­
food
Animals
(
poultry).
Data
for
cattle
cannot
be
extrapolated
to
poultry,
because
of
the
different
application
method
and
less
frequent
applications.
However,
individual
animals
are
less
likely
to
be
treated
directly
and
the
equipment
is
more
likely
to
be
automated.
As
a
result,
exposure
from
applying
dichlorvos
to
poultry
is
expected
to
be
much
lower
than
for
cattle,
and
no
separate
assessment
is
done.

4.
Domestic
Animal
Premises
­
Dairy
Barns.
An
average
dairy
barn
has
the
dimensions
30
ft
x
100
ft
x
9
ft
(
total
area
covered
is
5,340
ft
2
).
(
Dow,
M.,
1985).
Dichlorvos
is
applied
at
two
week
intervals
for
22
weeks,
one
barn
per
day.
A
1.0
percent
solution
of
dichlorvos
is
applied
using
a
low
pressure
hand
sprayer
at
a
rate
of
0.0115
lb
a.
i.
per
1000
ft
2
.
A
worker
wears
long
sleeve
shirt,
long
trousers,
shoes
and
impervious
gloves
at
a
minimum.
The
unit
exposure
varies
depending
on
the
equipment
used.

5.
Rail
cars
and
trucks.
Calculation
is
shown
for
treating
10
rail
cars
or
trucks
per
day.
Dermal
absorption
is
assumed
to
be
11
percent.
Applicators
are
assumed
to
wear
long
sleeve
shirts,
long
pants,
gloves,
and
a
respirator
(
90%
protection).
Coveralls,
although
required
on
some
labels,
are
not
included
for
surface
application.
An
applicator
treating
10
rail
cars
per
day
handles
0.28
lb
ai/
day.
The
dermal
unit
exposure
is
0.67
mg/
lb
ai,
and
the
inhalation
unit
exposure
is
0.0032
mg/
lb
ai.

0.28
lb
dichlorvos
x
0.67
mg/
lb
ai
x
0.11
(
dermal
absorpting
factor)
=
0.00030
mg/
kg/
day
70
kg
applicator
0.28
lb
dichlorvos
x
0.0032
mg/
lb
ai
=
0.000013
mg/
kg/
day
70
kg
applicator
6.
Feedlots
include
stockyards,
corrals,
holding
pens
and
other
areas
where
large
groups
of
animals
are
contained.
EPA
assumes
that
some
type
of
power
sprayer
capable
of
treating
a
large
number
of
animals
in
a
short
time
is
probably
used.
A
short
application
time
period
in
an
outdoor
or
partially
enclosed
area
would
minimize
exposure
to
less
than
that
of
dairy
applications.

7.
Manure.
The
MOE
is
expected
to
be
greater
than
100
for
manure
use.
Application
equipment
may
be
similar
to
those
used
in
a
dairy
barn;
however,
the
application
time
would
probably
be
less
and
the
treated
area
would
be
well
ventilated
­
either
outdoors
or
in
a
partially
enclosed
area.

8.
Garbage
Dumps.
Exposure
at
a
garbage
dump
is
believed
to
be
less
than
dairy
exposure.
Page
100
of
151
Table
9.2.
Summary
of
Occupational
Post­
Application
Exposure
and
Risk
Estimates
for
Dichlorvos
Current
Exposure
(
mg/
kg/
day)
Current
MOE
MOE
USES
NOTES
EXPOSURE
PATTERN1
Dermal
Inhalation
Dermal
Inhalation
Total
OCCUPATIONAL
EXPOSURE
1
Target
MOEs
for
all
short
term
post­
application
Occupational
Scenarios
are
30,
and
for
acute
postapplication
scenarios,
are
100.

i.
Mushroom
house
2
Reentry
(
12­
hour
REI)
Short­
term
0.0002
0.044
mg/
m
3
450
24
23
Reentry
(
24­
hour
REI)
Short­
term
0.0002
0.016
mg/
m
3
450
66
58
ii.
Greenhouse
3
Reentry
(
2
hour
REI)
Short­
term
0.0012
0.00035
mg/
m
3
80
3000
78
Reentry
(
12
hour
REI)
Short­
term
0.00012
<
0.00035
mg/
m
3
800
>
3000
>
650
Reentry
(
24
­
hour
REI)
Short­
term
<
0.00012
<
0.00035
mg/
m
3
>
800
>
3000
>
650
iii.
Food
Manufacturing
Plant
­

Reentry
(
24
hour
REI)
4
acute
0.00022
0.053
mg/
m
3
(
0.006
mg/
kg/
day)
3600
130
130
iv.
Warehouse
treatment
­

Reentry
(
24
hour
REI,
1
hr
exposure)
5
acute
0.00022
0.074
mg/
m
3
(
0.001
mg/
kg/
day)
3600
800
650
v.
Railcars
and
trucks
(
8
hr
REI)
6
Short­
term
0.0187
mg/
m
3
(
0.0010
mg/
kg/
day)
94
94
NOTES:
The
following
notes
define
the
assumptions
used
in
calculating
the
margins
of
exposure.
Page
101
of
151
1.
Risk
is
expressed
as
a
Margin
of
Exposure
(
MOE)

MOE
=
NOAEL
,
where
both
the
NOAEL
and
the
Exposure
are
expressed
in
mg/
kg/
day
or
mg/
m
3
Exposure
The
target
MOE
for
all
short
term
post­
application
occupational
exposure
is
30,
and
for
all
acute
post­
application
scenarios
is
100.

Occupational
Exposure
assumptions.
An
average
worker
weighs
70
kg
and
has
a
respiratory
volume
of
1.0
m
3
/
hour
(
NAFTA
Value).
At
a
minimum,
the
following
protective
clothing
was
used
in
the
exposure
scenarios:
gloves,
long­
sleeve
shirt,
and
long
pants.
Addition
of
a
respirator
to
the
PPE
requirements
would
reduce
estimated
inhalation
exposure
by
90%,
which
would
not
change
the
MOEs
by
more
than
a
factor
of
2.

2.
Mushroom
Houses
­
reentry.
For
reentry
exposure,
it
was
assumed
that
a
worker
reenters
a
ventilated
mushroom
house
12
or
24
hours
after
treatment
and
is
exposed
for
8
hours.
The
post­
application
exposures
for
mushroom
houses
were
derived
from
a
study
conducted
by
the
California
Department
of
Food
and
Agriculture
(
CDFA)

(
now
the
California
EPA)
in
which
air
and
surface
residues
were
measured
in
mushroom
houses
where
dichlorvos
had
been
applied
(
Maddy
1981,
Jaquith
1998d).

This
was
a
limited
study
measuring
surface
residues
and
air
concentrations
in
2­
4
mushroom
houses
over
24
hours.

Wipe
sampling
was
only
conducted
in
2
mushroom
houses,
preventing
any
analysis
of
the
distribution
of
surface
residues
in
these
facilities.
The
highest
surface
concentration,
0.026
µ
g/
cm
2
,
was
reported
3
hours
after
application.
The
last
sampling
point
was
at
12
hours
after
application,
when
the
surface
residues
averaged
0.007
µ
g/
cm
2
.
There
was
no
clear
trend
in
the
air
concentrations.
Air
samples
were
collected
at
30
minutes,
and
1,
3,
6,
12,
and
24
hours.
Only
two
samples
were
taken
at
the
24
hour
sampling
period.
The
air
concentrations
of
dichlorvos
averaged
0.022,
0.044,
and
0.016
mg/
m
3
,
at
6,
12,
and
24
hours
after
treatment,

respectively.
The
transfer
coefficient
was
obtained
from
the
ExpoSAC
policy
003,
to
be
2500
cm
2
/
hr.
Because
of
the
aeration
pattern
of
mushroom
houses,
the
volatility
of
dichlorvos,
and
dissipation
of
dichlorvos
in
mushroom
houses,
this
is
considered
to
be
a
short
term
exposure
scenario.
Respirators
are
not
worn
during
reentry.

Dermal
Exposure
(
µ
g/
kg/
day)
=
0.007
µ
g/
cm
2
x
2500
cm
2
/
hr
x
8
hr/
day
x
1/
70
kg
x
0.11
(
Absorb)

=
0.22
µ
g/
kg/
day
=
0.00022
mg/
kg/
day
Estimated
dermal
post­
application
risk
=
NOAEL
=
0.1
mg/
kg/
day
=
450
(
Target
MOE
=
30,
ARI
=
450/
30
=
15)

Exposure
0.00022
mg/
kg/
day
The
inhalation
risk
estimate
includes
a
factor
to
adjust
for
the
hours
of
exposure.
The
endpoint
converted
to
concentration
units
assumed
24
hours
exposure
per
day.

Workers
in
mushroom
houses
are
exposed
for
8
hours.

Estimated
inhalation
post­
application
risk
=
NOAEL
=
0.35
mg/
m
3
x
24hr
=
24
(
Target
MOE
=
30)

(
12
hour
REI)
Exposure
0.044
mg/
m
3
8
hr
The
label
REI
is
now
18
hours.

3.
Greenhouse
­
reentry.
The
dermal
exposure
for
reentry
into
greenhouses
following
the
use
of
dichlorvos
was
obtained
using
data
from
a
greenhouse
culture
textbook,

data
on
turf
transferable
residues
from
a
chlorpyrifos/
dichlorvos
turf
study
(
Goh,
K.
S.,
et.
al.
1986),
and
a
transfer
coefficient
of
2500
cm
2
/
hr,
from
the
ExpoSAC
Policy
003.
Inhalation
exposure
estimates
were
modeled
assuming
the
initial
concentration
at
the
maximum
rate,
assuming
first
order
kinetics
and
an
air
exchange
rate
from
a
textbook
(
Mastalerz,
1977).
This
is
considered
to
be
a
short­
term
exposure
scenario
(
Jaquith,
1998d).
Page
102
of
151
The
dislodgeable
foliar
residues
reported
in
the
Goh
study
were
0.04
µ
g/
cm
2
,
2
­
6
hours
after
application,
and
0.004
µ
g/
cm
2
,
10
hours
after
application
of
2
g
dichlorvos/
1000
ft
3
.

The
total
daily
dermal
exposure
that
would
occur
after
a
2
hour
REI
is
estimated
to
be:

Dermal
Exposure
(
µ
g/
kg/
day)
=
0.04
µ
g/
cm
2
x
2500
cm
2
/
hr
x
8
hrs/
day
x
0.11
(
dermal
absorption
factor)
x
1/
70
kg
=
1.25
µ
g/
kg/
day
(
0.00125
mg/
kg/
day)

Dermal
MOE
=
NOAEL
=
0.1
mg/
kg/
day
=
80
Exposure
0.00125
mg/
kg/
day
Estimated
inhalation
post­
application
risk
=
NOAEL
=
0.35
mg/
m
3
x
24
hr
=
3000
(
2
hour
REI)
Exposure
0.00035
mg/
m
3
8
hr
4.
Reentry
­
Food
manufacturing
plant.
Dichlorvos
can
be
applied
to
food
processing
facilities
with
wall­
mounted
automatic
foggers.
In
estimating
reentry
exposure
to
food
processing
facilities,
EPA
assumed
24
hours
elapsed
before
reentry
is
allowed,
as
required
on
labels;
and
that
workers
spend
8
hours
per
day
on
the
day
following
treatment.
Dichlorvos
is
applied
at
the
rate
of
2.0
grams
active
ingredient
per
1,000
ft
3
over
a
period
of
125
minutes
per
application.
Hand
rinses
were
done
and
air
concentrations
were
measured
at
0,
3,
6,
10,
22,
and
42
hours
after
application.
Dermal
exposure
was
measured
for
the
hands
only
and
represents
an
average
of
the
total
exposure
measured
for
three
work
stations.
Because
significant
exposure
occurs
for
only
one
day
and
occurs
sporadically,
this
is
considered
an
acute
reentry
scenario
and
MOEs
are
calculated
using
the
BMDL10
of
0.8
mg/
kg
for
inhibition
of
rat
cholinesterase.

The
dermal
exposure
calculated
in
the
original
review
(
Jaquith
1993c),
0.00027
mg/
kg/
day,
has
been
corrected
for
the
application
rate
(
2.0/
2.4),
resulting
in
a
dermal
exposure
estimate
of
0.00022
mg/
kg/
day.

The
dermal
MOE
=
0.8/.
00022
=
3600
Mean
air
concentrations
of
dichlorvos
in
a
food
handling
establishment
following
treatment
using
a
fogger
at
2.4
g
ai/
1000
ft
3
.
Means
include
samples
from
all
sites
and
two
different
heights.
(
Jaquith,
D.,
2000a;
Jaquith,
D,
1993c).

Hours
After
Application
Mean
Conc.
(
mg/
m
3
)
Conc.
Corrected
for
application
rate
(
mg/
m
3
)

0
10.0
8.3
3
2.7
2.2
6
0.62
0.52
10
0.37
0.31
22
0.13
0.11
42
0.052
0.043
An
exponential
decay
curve
C
=
C0
x
e
­
kt
was
fit
to
the
data
where
C0
=
0.93
mg/
m
3
and
k
=
0.10
/
hour.
The
corresponding
equation
for
average
concentration
over
the
interval
from
t1
to
t2
is
Cavg
=
C0
x
(
e
­
kt1
­
e­
kt2
)
/
k(
t2­
t1).
For
the
interval
from
24
to
32
hours,
the
average
concentration
is
0.053
mg/
m
3
.
The
dose
on
a
mg/
kg
basis
is:
Page
103
of
151
Dose
(
mg/
kg)
=
0.053
mg/
m
3
x
1.0
m
3
/
hr
x
8
hr
÷
70
kg
=
0.006
mg/
kg.

The
acute
inhalation
MOE
is:
MOE
=
0.8
÷
0.006
=
130
5.
Reentry
­
warehouse.
Dichlorvos
can
be
applied
to
food
warehouses
with
wall­
mounted
automatic
foggers.
In
estimating
reentry
exposure
to
warehouse
facilities,
EPA
assumed
24
hours
elapsed
before
reentry
is
allowed,
as
required
on
labels;
and
that
workers
spend
60
minutes
per
day
in
the
treated
area.
Dichlorvos
is
applied
at
the
rate
of
2.0
grams
active
ingredient
per
1,000
ft
3
over
a
period
of
125
minutes
per
application.
Dermal
exposure
was
measured
for
the
hands
only
and
represents
an
average
of
the
total
exposure
measured
for
three
work
stations.
Because
significant
exposure
occurs
for
only
one
day
and
occurs
sporadically,
this
is
considered
an
acute
reentry
scenario
and
MOEs
are
calculated
using
the
BMDL10
of
0.8
mg/
kg
for
inhibition
of
rat
cholinesterase.

The
dermal
exposure
is
described
in
footnote
(
4).

The
methodology
for
inhalation
exposure
and
risk
are
described
in
footnote
(
4).
Assuming
a
worker
reenters
a
treated
warehouse
24
hours
after
application
and
works
for
one
hour,
the
average
dichlorvos
concentration
in
the
interval
from
24
to
25
hours
is
0.074
mg/
m
3
.
The
dose
on
a
mg/
kg
basis
is:

0.074
mg/
m
3
x
1.0
m
3
/
hr
x
1
hr
/
70
kg
=
0.0010
mg/
kg/
day
MOE
=
0.8
mg/
kg/
day
=
800
0.0010
mg/
kg/
day
6.
Reentry
­
railcars
and
trucks.
Dichlorvos
can
be
applied
to
railcars
and
trucks
as
a
space
spray,
or
as
a
surface
spray.
Some
labels
allow
up
to
2
g
ai/
1000
ft
3
,
others
allow
up
to
2.5
g
ai/
1000
ft
3
.
The
initial
concentration
of
dichlorvos
from
2.5
g
ai/
1000
ft
3
would
be
88
mg/
m
3
.
The
concentration
at
later
time
intervals
can
be
calculated
from
the
equation,
Ct
=
C0
x
e
­
kt
,
where
k
=
1,
based
on
an
assumed
air
exchange
rate
of
1
air
change
per
hour.
In
estimating
reentry
exposure,
EPA
assumed
8
hours
elapsed
before
reentry
is
allowed,
and
that
workers
could
spend
1
hour
per
truck
or
railcar
and
could
load
4
railcars
or
trucks
per
day.
Workers
loading
rail
cars
or
trucks
would
not
be
expected
to
have
dermal
exposure
to
dichlorvos.
The
air
concentration
was
estimated
using
initial
air
concentrations
calculated
from
the
application
rate,
and
assuming
ventilation
similar
to
a
food
processing
establishment
(
k=
1).
This
exposure
scenario
was
considered
to
be
short
term
due
to
rapid
dissipation
of
dichlorvos.
(
Jaquith,
D.,
2005).

Integrating
the
equation
for
a
period
of
8
to
9
hours,

Ct
=
­
88
mg/
m
3
x
(
e
­
9
­
e
­
8
)
=
0.0187
mg/
m
3
0.0187
mg/
m
3
x
1.0
m
3
/
hr
x
1
hr/
truck
x
4
trucks
/
70
kg
=
0.0011
mg/
kg/
day
MOE
=
0.1
mg/
kg/
day
=
94
0.0011
mg/
kg/
day
There
is
considerable
uncertainty
about
the
air
exchange
rate.
Under
the
conditions
described,
the
air
exchange
rate
could
be
as
low
as
1/
3
per
hour
Page
104
of
151
10.0
Data
Needs
and
Label
Requirements
10.1
Toxicology
There
are
no
outstanding
toxicology
data
requirements.

10.2
Product
Chemistry
The
discrepancy
in
the
percent
of
active
ingredient
in
several
of
the
technicals
must
be
resolved.

10.3
Residue
Chemistry
The
residue
chemistry
database
for
dichlorvos
is
reasonably
complete.
All
labels
must
conform
to
the
use
pattern
reflected
in
the
residue
data
submitted.
The
following
data
requirements
remain
outstanding.

GLN
860.1380:
Storage
Stability
Data
The
Reregistration
requirements
for
storage
stability
data
are
not
fulfilled.
Information
pertaining
to
the
storage
intervals
and
conditions
of
samples
of
the
following
commodities,
from
studies
that
were
reviewed
in
the
Residue
Chemistry
Chapter
of
the
Guidance
Document,
must
be
submitted:
packaged
and
bagged
raw
agricultural
commodities
and
processed
food;
bulk
stored
raw
agricultural
commodities;
milk;
eggs;
and
meat,
fat,
and
meat
byproducts
of
dairy
cows
and
poultry.
Alternatively,
the
registrant
may
demonstrate
that
there
are
sufficient
residue
data
which
are
supported
by
storage
stability
data
to
support
all
registered
uses
of
dichlorvos.

The
available
storage
stability
data
indicate
that
residues
of
dichlorvos
are
stable
under
frozen
storage
conditions
for
up
to
90
days
in/
on
plant
commodities,
up
to
4.5
months
in/
on
peanuts,
and
up
to
8
weeks
in
animal
commodities.

GLN
860.1480:
Meat,
Milk,
Poultry,
Eggs
The
Reregistration
requirements
for
data
pertaining
to
this
guideline
topic
are
not
completely
fulfilled.
A
dermal
magnitude
of
the
residue
study
must
be
submitted
for
swine.
No
additional
data
are
required
for
milk
and
edible
tissues
of
ruminants,
and
for
eggs
and
edible
tissues
of
poultry.
Swine
use
is
on
the
labels
for
EPA
Reg.
Nos.
572­
246
and
47000­
130.

10.4
Occupational
and
Residential
Exposure
All
labels
must
conform
to
the
parameters
used
in
this
risk
assessment.
Protective
clothing
requirements
at
least
as
stringent
as
that
used
in
this
risk
assessment
must
be
added
to
the
label.
Labels
permitting
fogging
must
be
clarified
to
state
that
hand­
held
foggers
are
not
permitted,
and
that
the
applicator
must
be
outside
the
treated
area
during
application.
Page
105
of
151
The
greenhouse
exposure
study
requirement
has
been
satisfied
by
a
generic
study
on
malathion,
which
allowed
the
Agency
to
determine
a
transfer
coefficient
for
harvesting
greenhouse
grown
cut
flowers.
MRID
46513901,
(
Dole,
T
and
M.
Lloyd,
2005)

Dichlorvos
from
trichlorfon.
Outstanding
exposure
data
requirements
exist
for
trichlorfon.
A
TTR
study
with
analyses
for
trichlorfon
and
dichlorvos
in
the
turf
and
in
the
toddler
breathing
zone
above
the
turf
(
18")
is
requested
to
confirm
the
exposure
estimates
in
this
document.
The
study
must
be
conducted
at
an
appropriate
pH
(
approx.
7).
A
field
dissipation
study
may
be
substituted,
provided
it
meets
these
requirements.

GDLN
875.2100
Foliar
Residue
Dissipation
Study
(
replaces
GDLN
132­
1(
a))
GDLN
875.2400
Dermal
Exposure
(
replaces
GDLN
133­
3,
Dermal
Passive
Dosimetry)
GDLN
875.2500
Inhalation
Exposure
(
replaces
GDLN
133­
4,
Inhalation
Passive
Dosimetry)
Page
106
of
151
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Appendices
1.0
TOXICOLOGY
DATA
REQUIREMENTS
The
toxicology
data
requirements
(
40
CFR
158.340)
for
food
uses
for
dichlorvos
are
in
Table
1.
Use
of
the
new
guideline
numbers
does
not
imply
that
the
new
(
1998)
guideline
protocols
were
used.

Technical
Test
Required
Satisfied
870.1100
Oral
Toxicity......................................................................
870.1200
Dermal
Toxicity.................................................................
870.1300
Inhalation
Toxicity.............................................................
870.2400
Primary
Eye
Irritation
.........................................................
870.2500
Primary
Dermal
Irritation....................................................
870.2600
Dermal
Sensitization..........................................................
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
870.3100
Oral
Subchronic
(
rodent)
..................................................
870.3150
Oral
Subchronic
(
nonrodent)
............................................
870.3200
21­
Day
Dermal
..................................................................
870.3250
90­
Day
Dermal
..................................................................
870.3465
90­
Day
Inhalation
..............................................................
yes
yes
no
no
yes
yes
yes
a
yes
870.3700a
Developmental
Toxicity
(
rodent)........................................
870.3700b
Developmental
Toxicity
(
nonrodent)
.................................
870.3800
Reproduction.....................................................................
yes
yes
yes
yes
yes
yes
870.4100a
Chronic
Toxicity
(
rodent)
...................................................
870.4100b
Chronic
Toxicity
(
nonrodent).............................................
870.4200a
Oncogenicity
(
rat)
..............................................................
870.4200b
Oncogenicity
(
mouse)
.......................................................
870.4300
Chronic/
Oncogenicity........................................................
yes
yes
yes
yes
yes
yes
b
yes
yes
b
yes
yes
870.5100
Mutagenicity 
Gene
Mutation
­
bacterial..........................
870.5300
Mutagenicity 
Gene
Mutation
­
mammalian.....................
870.5xxx
Mutagenicity 
Structural
Chromosomal
Aberrations
.......
870.5xxx
Mutagenicity 
Other
Genotoxic
Effects............................
yes
yes
yes
yes
yes
yes
yes
yes
870.6100a
Delayed
Neurotox.
(
hen)
..................................................
870.6100b
90­
Day
Neurotoxicity
(
hen)
...............................................
870.6200a
Neurotox.
Screening
Battery
(
rat)
....................................
870.6200b
90
Day
Neuro.
Screening
Battery
(
rat)
.............................
870.6300
Developmental
Neurotoxicity.............................................
yes
no
yes
yes
yes
yes
yes
yes
yes
870.7485
General
Metabolism..........................................................
870.7600
Dermal
Penetration
...........................................................
yes
yes
yes
yes
Special
Studies
for
Ocular
Effects
Oral
(
rat)
............................................................................
Subchronic
Oral
(
rat).........................................................
Six­
month
Oral
(
dog).........................................................
no
no
no
a
=
subchronic
(
oral)
dog
study
is
satisfied
by
chronic
dog
study
b
=
chronic
toxicity
in
rats
and
oncogenicity
in
rats
are
satisfied
by
chronic
toxicity/
carcinogenicity
rat
study
Page
116
of
151
2.0
REFERENCES
FOR
TOXICOLOGY
STUDIES
Alternative
Selection
for
Acute
RfD:

Study
Selected:
Acute
Cholinesterase
Study
­
Humans
Non­
guideline
MRID:
44248802
Title:
Dichlorvos:
A
Study
to
Investigate
the
Effect
of
a
Single
Oral
Dose
on
Erythrocyte
Cholinesterase
Inhibition
in
Healthy
Male
Volunteers;
Gledhill,
AJ;
March
25,
1997
Executive
Summary:
Dichlorvos
was
administered
in
a
single
oral
dose
of
70
mg
(
equivalent
to
1
mg/
kg
bw)
in
corn
oil
by
capsule
to
fasted
young
healthy
male
volunteers.
Prior
to
dosing,
baseline
RBC
cholinesterase
activity
was
measured
on
study
days
­
22,
­
20,
­
18,
­
15,
­
13,
­
11,
­
8,
­
6,
­
4
and
immediately
prior
to
dosing.
The
study
subjects
were
medically
supervised
for
clinical
signs
and
body
temperature
changes
for
24
hours
and
for
RBC
cholinesterase
inhibition
for
up
to
fourteen
days
after
administration
of
the
DDVP
capsules.
Plasma
cholinesterase
was
not
measured
in
this
study.

Under
study
conditions,
no
adverse
clinical
signs
or
changes
in
body
temperature
were
reported.
When
the
group
mean
RBC
cholinesterase
activities
were
analyzed,
there
were
statistically
significant
reductions
(
p 
0.01)
from
the
predose
mean
on
days
5/
6,
day
7,
and
day
14.
These
statistically
significant
reductions
represent
percent
decreases
of
10,
12,
and
11%,
respectively.
No
reduction
in
RBC
cholinesterase
activity
was
apparent
at
other
reporting
periods.
The
individual
predose
values
used
to
calculate
the
mean
RBC
cholinesterase
activity
varied
by
17%
for
volunteer
1,
16%
for
volunteer
2,
6%
for
volunteer
3,
10%
for
volunteer
4,
7%
for
volunteer
5,
and
9%
for
volunteer
6.

The
NOAEL
for
RBC
cholinesterase
depression
is
1.0
mg/
kg
bw
and
a
LOAEL
was
not
established
in
the
study.

Although
the
study
results
indicate
that
a
significant
decrease
in
mean
RBC
cholinesterase
was
first
observed
at
5/
6
days
after
treatment,
with
significance
also
seen
at
7
and
14
days
posttreatment,
measurements
at
posttreatment
days
1
and
3
were
not
significantly
different
from
baseline.
These
results
are
inconsistent
with
known
information
on
the
chemical.
Namely,
given
the
rapid
bioavailability
and
metabolism
of
dichlorvos,
it
is
unlikely
that
a
significant
decrease
in
RBC
cholinesterase
would
first
be
observed
at
day
5/
6
posttreatment
and
not
also
at
days
1
and
3
posttreatment.
The
statistical
significance
observed
could
be
attributed
to
variation
among
individual
participants.

Lack
of
information
on
time
of
peak
effect.

In
the
acute
human
study,
the
first
cholinesterase
measurement
was
recorded
24
hours
after
dosing.
In
the
study
(
MRID
46153303)
on
the
measurement
of
RBC
and
brain
ChE
activity
in
pre­
weaning
and
adult
female
rats
treated
with
a
single
dose
of
15
mg/
kg
dichlorvos,
time­
course
data
demonstrate
that
the
time
of
peak
effect
for
both
RBC
and
brain
ChE
measurements
is
1­
3
hours
Page
117
of
151
post­
dosing.
Therefore,
the
absence
of
biologically
significant
RBC
ChE
depression
in
the
human
study
may
be
due
to
the
absence
of
blood
sampling
at
the
time
of
peak
effect
(
1­
3
hours),
since
in
the
human
study,
the
first
measurement
did
not
occur
until
24
hours
after
dosing.

Based
on
the
information
on
time
to
peak
effect,
we
conclude
that
the
lack
of
cholinesterase
measurements
prior
to
24
hours
post­
treatment
in
the
acute
human
study
may
have
influenced
the
apparent
NOAEL.
We
have
therefore
opted
not
to
use
the
acute
human
study
for
regulatory
purposes.

CITATION:
G.
Milburn
(
2003)
Dichlorvos:
developmental
neurotoxicity
study
in
rats.
Central
Toxicology
Laboratory,
Alderley
Park,
Macclesfield,
Cheshire,
UK.
Laboratory
report
number
CTL/
RR0886/
Regulatory/
Report,
November
10,
2003.
MRID
46153302.
Unpublished.

G.
Milburn
(
2003)
Dichlorvos:
preliminary
developmental
neurotoxicity
study
in
rats.
Central
Toxicology
Laboratory,
Alderley
Park,
Macclesfield,
Cheshire,
UK.
Laboratory
report
number
CTL/
RR00885/
Regulatory/
Report,
October
13,
2003.
MRID
46153301.
Unpublished.

SPONSOR:
Amvac
Chemical
Corporation.
EXECUTIVE
SUMMARY:

In
a
developmental
neurotoxicity
study
(
2003,
MRID
46153302,
study
RR0886)
Dichlorvos
(
99.0%
a.
i.,
batch
#
ST120700)
was
administered
to
30
time­
mated
female
Alpk:
APfSD
(
Wistar­
derived)
rats
per
group
by
gavage
in
de­
ionized
water
at
dose
levels
of
0,
0.1,
1.0,
or
7.5
mg/
kg
bw/
day
from
gestation
day
(
GD)
7
through
postnatal
day
(
PND)
7
and
direct
treatment
of
the
F1
offspring
was
carried
out
during
PND
8­
22,
inclusive.
On
PND
5,
litters
were
culled
to
8
pups
(
4/
sex
as
closely
as
possible),
and
litters
containing
fewer
than
7
pups
and/
or
fewer
than
3
pups
of
each
sex
were
removed
from
the
study.
The
dams
were
subjected
to
a
functional
observational
battery
(
FOB)
on
GDs
10
and
17
and
on
PNDs
2
and
9.
The
F1
offspring
were
observed
for
attainment
of
preputial
separation
or
vaginal
patency.
Animals
were
allocated
from
within
litters
for
use
in
the
following
investigations:
functional
observational
battery
assessments
(
PNDs
5,
12,
22,
36,
46,
and
61);
locomotor
activity
assessment
(
PNDs
14,
18,
22,
and
60);
auditory
startle
habituation
(
PNDs
23
and
61),
water
maze
testing
(
PND
24­
27
or
PND
59­
62);
and
post
mortem
investigations
including
brain
weight,
neuropathology,
and
morphometry
(
PNDs
12
and
63).
Dosing
was
based
on
a
preliminary
developmental
neurotoxicity
study
in
rats
(
MRID
46153301).

One
high­
dose
female
was
sacrificed
on
LD
3
due
to
clinical
signs
(
pallor,
piloerection,
and
slightly
hunched
posture
and
thin
appearance)
and
had
a
pale
liver
at
necropsy.
One
mid­
dose
female
died
on
GD
24
due
to
parturition
difficulties.
There
were
no
treatment­
related
effects
on
maternal
body
weight,
FOB
parameters,
or
gestation
length.
The
maternal
NOAEL
is
7.5
mg/
kg/
day,
the
highest
dose
tested.
A
maternal
LOAEL
was
not
established.
Page
118
of
151
During
LD
1­
5,
the
control,
low­,
mid­,
and
high­
dose
groups,
respectively,
had
pup
mortality
of
22.6,
17.4,
17.5,
and
28.1%,
and
there
were
total
litter
losses
of
20.0,
10.0,
17.9,
and
18.5%
of
the
litters
in
these
same
respective
groups.
There
were
2
total
litter
resorptions
in
the
high­
dose
group.
The
number
of
litters
available
which
were
used
for
F1
offspring
was
23,
21,
21,
and
14
and
the
viability
indices
were
77.4,
82.6,
82.5,
and
69.0%
for
the
control,
low,
mid,
and
high
dose
groups,
respectively.

Due
to
the
low
number
of
pups
available
in
the
high
dose
group,
it
was
necessary
to
combine
this
study
(
RR0886)
with
a
repeat
study
(
2004,
MRID
46239801;
study
No.
RR0988)
consisting
of
controls
and
a
dose
level
of
7.5
mg/
kg
in
order
to
have
sufficient
pups
for
all
assessments.

The
DNT
Committee
determined
that
the
two
DNT
studies
combined
(
RR0886
and
RR0988)
had
acceptable
numbers
of
total
pups
examined
in
the
controls
and
high
dose
groups
(>
35
pups/
sex
examined
in
combined
studies)
and,
therefore,
the
developmental
results
of
the
combined
studies
could
be
evaluated
for
the
NOAEL/
LOAEL.
The
classification
of
the
studies
taken
together
was
changed
from
unacceptable/
non­
guideline
to
Acceptable/
non­
guideline.
A
comparison
of
the
developmental
findings
showed
that
the
auditory
startle
reflex
habituation
Vmax
in
PND
23
high
dose
males
in
study
RR0886
had
statistically
significant
increases
(
37­
49%)
in
4
out
of
5
blocks
and
study
RR0988
had
increases
(
7­
15%),
although
not
statistically
significant,
in
this
same
Vmax
parameter
in
PND
23
high
dose
males
in
5
out
of
5
blocks
in
comparison
to
controls
for
each
study.

Therefore,
the
developmental/
offspring
NOAEL
was
determined
to
be
1.0
mg/
kg/
day
(
based
on
study
RR0886)
and
the
developmental/
offspring
LOAEL
was
7.5
mg/
kg/
day
(
based
on
both
studies
RR0886
and
RR0988)
with
the
effect
being
increases
in
auditory
startle
reflex
habituation
Vmax
in
PND
23
high
dose
males
in
both
studies.

This
study
when
combined
with
the
accompanying
study
is
classified
Acceptable/
non­
guideline
and
may
be
used
for
regulatory
purposes.
It
does
satisfy
the
guideline
requirement
for
a
developmental
neurotoxicity
study
in
rats
[
OPPTS
870.6300,
§
83­
6;
OECD
426
(
draft)],
pending
review
of
the
positive
control
data.

CITATION:
G.
M.
Milburn
(
2004)
Dichlorvos:
supplemental
developmental
neurotoxicity
study
in
rats.
Central
Toxicology
Laboratory,
Alderley
Park,
Macclesfield,
Cheshire,
UK
SK10
4TJ.
Laboratory
report
number
CTL/
RR0988/
Regulatory/
Report,
January
28,
2004.
MRID
46239801.
Unpublished.

SPONSOR:
Amvac
Chemical
Corporation.

EXECUTIVE
SUMMARY:
In
a
preliminary
developmental
neurotoxicity
study
(
MRID
46153301)
Dichlorvos
(
99.0%
a.
i.,
batch
#
ST120700)
was
administered
by
gavage
in
de­
ionized
water
to
15
time­
mated
female
Alpk:
APfSD
(
Wistar­
derived)
rats
per
dose
at
dose
levels
of
0,
0.1,
1.0,
or
7.5
mg/
kg
bw/
day
from
gestation
day
(
GD)
7
through
postnatal
day
(
PND)
22.
In­
life
observations
included
maternal
clinical
signs,
body
weight,
and
food
consumption
(
during
gestation)
and
the
number,
survival,
clinical
signs,
and
body
weight
of
the
pups.
Erythrocyte
(
RBC)
and
whole
Page
119
of
151
brain
acetylcholinesterase
(
AChE)
activities
were
measured
as
follows:
in
5
dams/
group
on
GD
22;
in
5
dams/
group
on
PND
22;
in
selected
fetuses
from
the
dams
killed
on
GD
22
(
blood
from
sufficient
fetuses
to
attain
adequate
pooled
sample
volume
and
whole
brain
from
4
fetuses/
sex/
litter);
and
in
5
pups/
sex/
group
(
1
per
litter
where
possible)
on
each
of
PNDs
2,
8,
15,
and
22.
Plasma
AChE
activity
was
not
measured.

There
were
no
maternal
deaths
during
the
study.
Three
dams
had
abnormal
clinical
signs:
one
control
dam
with
piloerection
on
day
26;
one
mid­
dose
dam
with
observations
of
paleness
(
days
24­
26),
hunched,
subdued
behavior
(
day
26),
and
a
total
litter
loss
by
day
26
(
LD
3);
and
one
high­
dose
dam
with
irregular
breathing
on
days
25­
27.
There
were
no
treatment­
related
effects
on
maternal
food
consumption,
maternal
body
weight,
or
gestation
length.
The
study
author
mentioned
body
weight
decreases
in
high­
dose
dams
beginning
on
LD
11,
but
these
were
of
insufficient
magnitude
to
be
considered
biologically
significant
(
just
3­
4%
less
than
controls).
Under
the
conditions
of
this
study,
the
LOAEL
for
maternal
systemic
toxicity
(
other
than
acetylcholinesterase
inhibition)
is
not
identified,
and
the
NOAEL
is
greater
than
or
equal
to
7.5
mg/
kg
bw/
day.

There
were
no
treatment­
related
effects
on
the
overall
proportion
of
pups
born
alive,
the
mean
percentage
of
live
pups
per
litter,
or
live
litter
size
on
LD
1.
Pup
survival,
body
weight,
and
clinical
signs
were
unaffected
by
treatment.
Two
dams
had
total
litter
losses:
one
mid­
dose
dam
had
a
total
litter
loss
by
LD
3,
and
one
low­
dose
dam
had
a
total
litter
loss
(
of
1
pup)
by
LD
2.
An
increased
proportion
of
male
pups
in
the
mid­
dose
group
(
64.8%
vs.
46.2%
for
controls;
p<
0.01)
was
considered
incidental
to
treatment
because
there
was
no
similar
finding
at
the
highest
dose
level.
Under
the
conditions
of
this
study,
the
LOAEL
for
offspring
toxicity
(
other
than
acetylcholinesterase
inhibition)
is
not
identified,
and
the
NOAEL
is
greater
than
or
equal
to
7.5
mg/
kg
bw/
day.

In
maternal
animals,
RBC
AChE
activity
was
biologically
significantly
inhibited
at
the
mid­
and
highdose
treatment
levels
on
GD
22
by
25%
and
48%,
respectively
(
p<
0.01)
and
on
LD
22
by
24%
and
50%,
respectively
(
p<
0.05
and
p<
0.01).
RBC
AChE
activity
was
also
inhibited
in
high­
dose
male
and
female
(
GD
22)
fetuses
by
28%
(
p<
0.5)
[
p<
0.05]
and
21%
(
n.
s.),
respectively.
There
were
no
treatment­
related
effects
on
RBC
AChE
activity
in
male
or
female
pups.
The
LOAEL
for
dichlorvos
erythrocyte
acetylcholinesterase
inhibition
in
maternal
rats
is
1.0
mg/
kg
bw/
day,
with
a
NOAEL
of
0.1
mg/
kg
bw/
day.
The
LOAEL
for
erythrocyte
acetylcholinesterase
inhibition
in
offspring
or
fetuses
is
7.5
mg/
kg
bw/
day
(
based
on
male
and
female
fetuses
on
GD
22),
and
the
NOAEL
is
1.0
mg/
kg
bw/
day.

In
maternal
animals,
whole
brain
AChE
activity
was
biologically
significantly
inhibited
in
high­
dose
animals
on
GD
22
and
LD
22
by
59%
and
67%,
respectively
(
p<
0.01).
Brain
AChE
activity
was
also
inhibited
in
high­
dose
male
and
female
(
GD
22)
fetuses
by
16%
(
p<
0.5)
[
p<
0.05]
and
21%,
respectively
(
p<
0.01).
There
were
no
treatment­
related
effects
on
brain
AChE
activity
in
male
or
female
pups.
The
LOAEL
for
brain
acetylcholinesterase
inhibition
in
maternal
animals
is
7.5
mg/
kg
bw/
day,
with
a
NOAEL
of
1.0
mg/
kg
bw/
day.
The
LOAEL
for
brain
acetylcholinesterase
inhibition
in
offspring
or
fetuses
is
7.5
mg/
kg
bw/
day
(
based
on
male
and
female
fetuses
on
GD
22),
and
the
NOAEL
is
1.0
mg/
kg
bw/
day.
Page
120
of
151
Based
on
the
results
of
this
study,
dose
levels
of
0,
0.1,
1.0,
and
7.5
mg/
kg
bw/
day
were
chosen
for
the
main
study.

CITATION:
Milburn,
G.
M..
(
2003)
Dichlorvos:
time
course
of
cholinesterase
inhibition
in
pre­
weaning
and
adult
rats.
Central
Toxicology
Laboratory,
Cheshire,
UK
SK10
4TJ.
Doc.
No.
CTL/
AR7310/
Regulatory/
Report.
26­
SEPT­
2003.
MRID
46153303.
Unpublished.

Twomey,
K.
(
2002)
Dichlorvos
(
DDVP):
Acute
cholinesterase
inhibition
study
in
rats.
Central
Toxicology
Laboratory,
Cheshire,
UK
SK104T3.
Laboratory
report
number
CTL/
AR7079/
SUM/
Regulatory/
Report;
Study
No.
AR7079,
30­
MAY­
2002.
MRID
45805701.
Unpublished.

Twomey,
K.
(
2002)
Dichlorvos
(
DDVP):
Second
acute
cholinesterase
inhibition
study
in
rats.
Central
Toxicology
Laboratory,
Cheshire,
UK
SK104TJ.
Laboratory
report
number
CTL/
AR7126/
SUM/
Regulatory/
Report;
Study
No.
AR7126,
19­
JUNE­
2002.
MRID
45805702.
Unpublished.

Twomey,
K.
(
2002)
Dichlorvos
(
DDVP):
Third
acute
cholinesterase
inhibition
study
in
rats.
Central
Toxicology
Laboratory,
Alderley
Park,
Macclesfield,
Cheshire,
UK
SK104TJ.
Laboratory
report
number
CTL/
AR7138/
Regulatory/
Report;
Study
No.
AR7138,
26­
JUNE­
2002.
MRID
45805703.
Unpublished.

Moxon,
M.
E.
(
2002)
Dichlorvos:
Acute
cholinesterase
inhibition
study
in
preweaning
rats.
Central
Toxicology
Laboratory,
Cheshire,
UK
SK104T3.
Laboratory
report
number
CTL/
AR7147/
Regulatory/
Report;
Study
No.
AR7147,
22­
NOV­
2002.
MRID
45842301.
Unpublished.

Moxon,
M.
E.
(
2003)
Dichlorvos:
Repeat
dose
cholinesterase
inhibition
study
in
pre­
weaning
and
young
adult
rats.
Central
Toxicology
Laboratory,
Cheshire,
UK
SK104TJ.
Laboratory
report
number
CTL/
KR1490/
Regulatory/
Report;
Study
No.
KR1490,
24­
OCT­
2002.
MRID
46153304.
Unpublished.

SPONSOR:
AMVAC,
Los
Angeles,
CA
EXECUTIVE
SUMMARY:
In
a
series
of
special
comparative
cholinesterase
inhibition
(
ChEI)
studies,
Dichlorvos
(
DDVP;
99%
a.
i.,
lot
#
ST
120700)
was
administered
by
gavage
to
groups
of
either
Sprague­
Dawley
or
Wistar
rats.
For
time­
course
evaluation
(
MRID
46153303)
5
females/
group
were
given
a
single
oral
dose
of
0
or
15
mg/
kg
on
PND
15
or
42
and
sacrificed
1,
3,
8,
24,
or
72
hours
later.
In
three
acute
studies
(
MRIDs
45805701,
45805702,
45805703)
groups
of
5
adult
rats/
sex
were
given
a
single
oral
dose
of
0,
1,
5,
15,
or
35
mg/
kg
and
sacrificed
one
hour
post­
dosing
or
on
post­
dosing
days
8
and
15.
In
a
fourth
acute
study,
groups
of
5
pre­
weaning
Page
121
of
151
rats/
sex
were
given
a
single
oral
dose
of
0,
1,
5,
or
15
mg/
kg
on
PND
8,
15,
or
22
and
terminated
one
hour
post­
dosing.
Finally
repeated
administration
was
studied
by
giving
seven
daily
doses
of
0,
0.1,
7.5,
or
15
mg/
kg/
day
to
groups
of
5
rats/
sex
beginning
on
either
PND
12
or
42;
animals
were
sacrificed
one
hour
after
the
last
dose.
RBC
and
brain
ChE
activities
were
measured
in
all
animals
in
each
study.
Plasma
enzyme
activity
was
not
measured
in
any
study.

Based
on
the
analytical
data
for
MRID
45805701,
the
low­
dose
animals
were
actually
dosed
with
2.1
mg/
kg,
rather
than
the
desired
dose
of
1.0
mg/
kg/
day.
For
the
remaining
studies,
the
analytical
data
indicated
that
the
mixing
procedure
was
adequate
and
that
the
difference
between
nominal
and
actual
dosage
to
the
study
animals
was
acceptable
for
all
studies.

At
a
single
dose
of
35
mg/
kg,
one
female
died
with
cholinergic
signs
and
four
males
were
killed
for
humane
reasons
due
to
severe
toxicity.
The
remaining
animals
of
both
sexes
given
35
mg/
kg
displayed
some
or
all
of
the
following
signs:
decreased
activity,
lachrymation,
miosis,
irregular
breathing,
clonic
convulsions,
tremors/
fasciculations,
prostration,
decreased
righting
and
splay
reflexes,
and
salivation.
A
single
dose
of
15
mg/
kg
resulted
in
miosis
and
fasciculations
in
one
adult
female,
and
tremors
in
one
male
and
one
female
on
PND
8
and
one
female
on
PND
22.
No
treatment
related
clinical
signs
were
observed
in
animals
of
the
1
or
5
mg/
kg
dose
groups
following
acute
exposure.

Following
repeated
exposure
of
pre­
weaning
rats,
tremors
were
observed
in
5/
5
males
and
5/
5
females
at
15
mg/
kg/
day
on
3­
5
days
of
the
dosing
interval.
In
young
adult
rats
at
15
mg/
kg/
day,
tremors
were
observed
in
3/
5
males
and
5/
5
females
on
one
to
four
days
of
the
dosing
interval.
In
addition,
tremors
were
seen
in
one
adult
male
after
the
last
dose
of
7.5
mg/
kg/
day.
No
clinical
signs
of
toxicity
were
observed
in
the
remaining
groups.

Acute
exposure
to
doses
 
5
mg/
kg
resulted
in
clear
dose­
related
inhibition
of
enzyme
activity
in
both
compartments
in
all
groups.
At
1
mg/
kg,
RBC
enzyme
activity
was
significantly
inhibited
in
PND
8
females,
and
PND
15
males
and
females,
but
not
adults.
Brain
enzyme
activity
from
animals
treated
with
1
mg/
kg
was
not
significantly
inhibited
in
adult
or
pre­
weaning
males
and
females.
Although
there
was
inhibition
of
brain
enzyme
activity
at
the
low
dose
in
MRID
45805701,
the
actual
analytical
dose
at
this
level
was
2.1
mg/
kg
and
not
1
mg/
kg.
Repeat
of
the
1
mg/
kg
dose
level
was
identified
as
a
NOAEL
for
brain
enzyme
inhibition
as
demonstrated
in
other
acute
studies.

Two
studies
included
recovery
groups
held
for
up
to
15
days
post­
exposure.
RBC
enzyme
activity
of
males
and
females
treated
with
35
mg/
kg
remained
slightly
inhibited
by
9­
15%
at
8
days
after
exposure.
This
is
not
considered
biologically
significant.
No
inhibition
of
RBC
enzyme
activity
was
seen
at
any
other
dose
at
8
or
15
days
post­
dosing.
Brain
enzyme
activity
was
not
affected
at
any
dose
during
the
recovery
interval.
Brain
and
RBC
enzyme
activities
were
maximally
inhibited
one
hour
after
dosing
in
both
adult
and
pre­
weaning
female
rats.
Thereafter,
ChE
inhibition
in
both
compartments
decreased
to
approximately
control
levels
by
8
hours
post­
dosing.

Dose­
related
inhibition
of
RBC
and
brain
ChE
activities
was
also
apparent
after
repeated
dosing
in
both
adult
and
pre­
weaning
rats.
Biologically
significant
inhibition
of
RBC
enzyme
activity
(>
50%)
occurred
at
doses
of
7.5
and
15
mg/
kg/
day
in
both
sexes
of
adults
and
pre­
weaning
and
at
the
low
Page
122
of
151
dose
for
adult
animals
(
11­
17%).
Brain
enzyme
activity
was
statistically
and
biologically
inhibited
in
both
sexes
at
doses
of
7.5
and
15
mg/
kg/
day
for
adults
(>
50%)
and
at
all
doses
for
pups
(>
20%).

For
acute
exposure:

the
adult
LOAEL
for
brain
ChEI
is
5
mg/
kg
for
males
and
females
the
adult
NOAEL
for
brain
ChEI
is
1
mg/
kg
for
males
and
females;

the
offspring
LOAEL
for
brain
ChEI
is
5
mg/
kg
(
both
sexes)
the
offspring
NOAEL
for
brain
ChEI
is
1
mg/
kg
(
both
sexes)

the
adult
LOAEL
for
red
blood
cell
ChEI
is
5
mg/
kg
(
both
sexes)
the
adult
NOAEL
for
red
blood
cell
ChEI
is
1
mg/
kg
(
both
sexes);

the
offspring
LOAEL
for
red
blood
cell
ChEI
is
1
mg/
kg
(
both
sexes)
the
offspring
NOAEL
for
red
blood
cell
ChEI
is
not
identified.

For
acute
exposure,
the
overall
adult
LOAEL
for
cholinesterase
inhibition
in
rats
is
5
mg/
kg
based
on
enzyme
inhibition
in
brain
and
red
blood
cells;
the
adult
NOAEL
is
1
mg/
kg.

For
acute
exposure,
the
overall
offspring
LOAEL
for
cholinesterase
inhibition
in
rats
is
1
mg/
kg
based
on
enzyme
inhibition
in
red
blood
cells;
the
offspring
NOAEL
was
not
identified.

For
repeated
exposure:

the
adult
LOAEL
for
brain
ChEI
is
7.5
mg/
kg/
day
(
both
sexes)
the
adult
NOAEL
for
brain
ChEI
is
0.1
mg/
kg/
day;

the
offspring
LOAEL
for
brain
ChEI
is
0.1
mg/
kg/
day
(
both
sexes)
the
offspring
NOAEL
for
brain
ChEI
is
not
identified;

the
adult
LOAEL
for
red
blood
cell
ChEI
is
0.1
mg/
kg/
day
(
both
sexes)
the
adult
NOAEL
for
red
blood
cell
ChEI
is
not
identified;

the
offspring
LOAEL
for
red
blood
cell
ChEI
is
7.5
mg/
kg/
day
(
both
sexes)
the
offspring
NOAEL
for
red
blood
cell
ChEI
is
0.1
mg/
kg/
day;

For
repeated
exposure,
the
overall
adult
LOAEL
for
cholinesterase
inhibition
in
rats
is
0.1
mg/
kg/
day
based
on
enzyme
inhibition
in
red
blood
cells;
the
adult
NOAEL
is
not
identified.

For
repeated
exposure,
the
overall
offspring
LOAEL
for
cholinesterase
inhibition
in
rats
is
0.1
mg/
kg/
day
based
on
enzyme
inhibition
in
brain;
the
offspring
NOAEL
is
not
identified.

The
cholinesterase
activity
measurements
following
an
acute
oral
dose
of
dichlorvos
demonstrate
approximately
equal
susceptibility
between
juvenile
and
adult
rats.
In
contrast,
results
from
repeated
Page
123
of
151
exposures
show
that
juvenile
rats
are
more
susceptible
than
adults
for
brain
ChEI.
In
pups
the
brain
ChE
activity
appeared
to
be
more
sensitive
than
RBC
enzyme
activity.
This
susceptibility
for
brain
cholinesterase
was
observed
in
terms
of
the
dose
level
at
which
an
effect
was
observed
(
i.
e.,
the
LOAEL
for
brain
cholinesterase
inhibition
was
lower
for
juveniles
than
for
adults).
However,
the
LOAEL
for
RBC
enzyme
inhibition
was
lower
for
adults
than
for
juvenile
rats.
The
fact
that
brain
enzyme
activity
in
young
animals
was
the
most
sensitive
to
inhibition
by
the
test
article
is
of
concern
for
potential
developmental
neurotoxicity.

Taken
together
these
studies
are
classified
Acceptable/
Non­
guideline
for
the
determination
of
RBC
and
brain
cholinesterase
activities
following
treatment
with
dichlorvos
in
adult
and
juvenile
rats.
Main
deficiencies
include
omission
of
plasma
measurements
and
lack
of
assessment
in
dams
and
fetuses
on
GD
20.

870.6100
(
81­
7)
Acute
Delayed
Neurotoxicity
­
Hen.
MRID
41004702
CITATION:
Beavers,
J.;
Driscoll,
C.;
Dukes,
V.;
et
al.
(
1988)
DDVP:
An
Acute
Delayed
Neurotoxicity
Study
in
Chickens:
Final
Report:
Project
No.
246­
103.
Unpublished
study
prepared
by
Wildlife
International
Ltd.
86
p.
(
MRID
41004702
EXECUTIVE
SUMMARY:
In
an
acceptable
acute
delayed
neurotoxicity
study
(
MRID
41004702),
groups
of
ten
chickens
were
exposed
either
to
vehicle
(
distilled
water),
DDVP
at
16.5
mg/
kg,
or
the
positive
control,
Tri­
o­
tolyl
Phosphate
(
TOCP),
at
600
mg/
kg
in
corn
oil.
All
birds
treated
with
DDVP
were
administered
an
intramuscular
injection
of
atropine
sulfate
at
5
mg/
kg
concurrent
with
DDVP
dosing
(
the
oral
LD50
value
of
DDVP
in
chickens
not
administered
atropine
is
reported
at
16.15
mg/
kg);
atropine
also
was
administered
at
2
mg/
kg
on
an
individual
basis
as
needed
to
DDVP­
treated
birds.

After
21
days,
DDVP­
treatment
and
vehicle
control
birds
were
redosed
(
with
atropine
treatment
as
previously)
and
observed
for
an
additional
21
days
before
sacrifice.
TOCP­
treated
birds
were
sacrificed
21
days
after
the
initial
dose.

During
the
first
forced
locomotor
activity
evaluation
on
day
3,
two
hens
(
G30
and
G37)
of
the
DDVP­
treated
group
displayed
slight
to
moderate
ataxia,
and
refused
to
walk
or
perform
the
second
walk.
By
day
7
(
the
second
evaluation)
hen
G37
was
noted
as
being
slightly
ataxic
when
dropped,
appeared
normal
during
the
hop,
but
refused
to
walk
alone.
This
bird
appeared
normal
when
standing
or
walking
in
a
group,
but
refused
to
move
when
alone;
this
hen
continued
to
refuse
to
walk
alone
at
each
evaluation
except
for
day
25.
On
days
36
and
39,
the
same
hen
also
refused
to
hop.
However,
when
observed
in
a
group,
this
bird
did
not
appear
ataxic,
and
appeared
to
move
in
a
normal
manner.

On
histopathological
examination,
bird
G37
showed
swelling
of
the
axis
cylinder
and
nerve
fiber
degeneration
in
the
sciatic
nerve.
Nerves
from
5/
10
positive
control
(
TOCP­
treated)
hens
showed
evidence
of
peripheral
neuropathy,
while
those
from
5/
10
hens
showed
no
significant
neural
degenerative
lesions;
however,
3/
5
of
these
hens
had
exhibited
slight
to
moderate
ataxia
during
Page
124
of
151
locomotor
assessments.
In
summary,
there
were
no
brain
or
spinal
cord
degenerative
changes
in
any
of
the
control,
TOC,
or
DDVP­
treated
groups.
However,
there
were
sciatic
nerve
degenerative
changes
in
0/
10,
5/
10,
and
1/
10
in
the
negative
control,
TOCP,
and
DDVP
groups,
respectively.

Although
the
authors
considered
the
results
equivocal,
the
findings
have
been
interpreted
by
HED
as
indicating
a
positive
result
for
DDVP
for
acute
delayed
neurotoxicity.

870.3100
(
82­
1)
13­
Week
Gavage
Study
in
Sprague­
Dawley
Rats
­
MRID
41004701
CITATION:
Kleeman,
J.
(
1988)
13­
Week
Gavage
Toxicity
Study
with
DDVP
in
Rats:
Final
Report:
Project
ID:
HLA
6274­
102.
Unpublished
study
pre­
pared
by
Hazleton
Laboratories
America,
Inc.
294
p.
MRID
41004701.

EXECUTIVE
SUMMARY:
In
an
acceptable
13­
week
subchronic
study
(
MRID
41004701),
Crl:
CDR(
SD)
BR
rats,
10/
sex/
group,
were
gavaged
with
0,
0.1,
1.5
or
15
mg
DDVP/
kg/
day,
5
days/
week,
"
for
at
least
13
weeks."
The
following
(
Table
5)
summarizes
possible
effects:

Table
5.

Controls
0.1
mg
DDVP/
kg/
day
1.5
mg
DDVP/
kg/
day
15
mg
DDVP/
kg/
day
Effect
M
F
M
F
M
F
M
F
Reduced
RBC
count,
hemoglobin
&
hematocrit
Week
14
­
­
­
­
+
­
+
+

Higher
Mean
Corpuscular
Volume
­
­
­
­
­
­
­
+

Higher
Cholesterol
­
­
­
­
­
­
+
­

Reduced
Plasma
ChE
Week
7
Week
14
­
­
­
­
­
­
­
­
+
+
+
+
+
+
+
+

Reduced
RBC
ChE
Week
7
Week
14
­
­
­
­
­
­
­
+
+
+
+
+
+
+
+
+

Reduced
Brain
ChE
(
termination)
­
­
­
­
­
­
+
+

In
addition,
salivation
and/
or
urine
stains
were
noted
in
some
high­
dose
males
and
females
at
approximately
30
to
60
minutes
post­
dosing.
According
to
Table
12
(
p.
52)
of
MRID
41004701,
at
terminal
sacrifice
2/
10
high­
dose
and
1/
10
low­
dose
females
(
but
no
control
females)
had
generalized
retinal
atrophy.
On
page
79
"
unilateral
retinal
degeneration"
occurred
in
1/
9
control
females,
1/
10
in
the
low­
dose
group,
0/
10
in
the
mid­
dose,
and
2/
10
in
the
high­
dose.
Males
in
the
high­
dose
group
had
a
noticeably
(
but
not
significantly)
elevated
mean
liver
weight
at
termination
Page
125
of
151
(
14.14
g
vs.
a
control
value
of
12.46
g).
However,
the
mean
liver­
to­
body
weight
ratio
was
significantly
(
p
 
0.05)
elevated
(
to
a
value
of
0.0293
vs.
a
control
value
of
0.0267).

The
following
mean
plasma
and
RBC
cholinesterase
measurements
were
obtained
for
weeks
7
and
14:

Table
6.

Males
(
Week
7)
Females
(
Week
7)

Dosage
Level
(
mg/
kg/
day)
Plasma
ChE
mu/
mL
Mean
(
S.
D.)
RBC
ChE
mu/
mL
Mean
(
S.
D.)
Plasma
ChE
mu/
mL
Mean
(
S.
D.)
RBC
ChE
mu/
mL
Mean
(
S.
D.)

0
318
(
67.3)
1195
(
163.1)
813
(
326.2)
1269
(
246.9)

0.1
285
(
32.0)
1166
(
244.3)
933
(
382.1)
1148
(
125.9)

1.5
226*(
48.5)
903*(
138.0)
692
(
89.7)
956*(
145.8)

15
112*(
24.2)
629*(
109.3)
338*(
79.0)
740*(
95.4)

*
Reported
as
statistically
significant,
with
p
 
0.05.
Data
are
from
Tables
13
and
14,
p.
53
and
54
of
MRID
41004701.

Table
7.

Males
(
Week
14)
Females
(
Week
14)

Dosage
Level
(
mg/
kg/
day)
Plasma
mu/
m
Mean
(
S
RBC
C
mu/
m
Mean
(
S
Plasma
mu/
m
Mean
(
S
RBC
C
mu/
m
Mean
(
S
0
314
(
56
1358
(
14
1091
(
46
1321
(
8
0.1
282
(
59
1247
(
11
1150
(
48
1212*(
8
1.5
259
(
69
1014*
(
6
1020
(
25
1002*(
8
15
204*(
45
787*(
10
575*(
14
874*(
8
*
Reported
as
statistically
significant,
with
p
 
0.05.
Data
are
from
Tables
13
and
14,
p.
53
and
54
of
MRID
41004701.

According
to
MRID
41004701
(
p.
29):
"
The
apparent
decrease
of
inhibitory
effect
at
week
14
[
as
compared
to
week
7]
may
have
been
due
to
a
longer
post­
treatment
interval
before
blood
collection
and
partial
recovery
of
cholinesterase
activity."
Page
126
of
151
The
following
mean
brain
cholinesterase
measurements
were
obtained
at
termination:

Table
8.

Dosage
Level
(
mg/
kg/
day)
Males
Brain
ChE
mu/
mL
Mean
(
S.
D.)
Females
Brain
ChE
mu/
mL
Mean
(
S.
D.)

0
1105
(
376.6)
1338
(
490.0)

0.1
1213
(
656.4)
1290
(
376.2)

1.5
1060
(
183.2)
1290
(
336.5)

15
791*(
290.0)
680*(
216.6)

*
Reported
as
statistically
significant,
with
p
 
0.05.

In
the
review
[
HED
Doc.
No.
007448]
it
is
stated
that:
"
The
data
presented
demonstrate
that
administration
of
DDVP
at
doses
of
0,
0.1,
1.5
and
15
mg/
kg[/
day]
resulted
in
no
adverse
effect
on
body
weight
or
food
consumption.
Although
hematology
parameters
were
reduced,
it
is
doubtful
whether
the
reductions
were
biologically
significant,
because
the
reductions
were
within
ten
percent
of
control
values.
Plasma
and
RBC
cholinesterase
activity
[
sic]
were
reduced
in
mid
and
high
dose
animals,
and
RBC
cholinesterase
activity
was
reduced
in
0.1
mg/
kg[/
day]
females
at
14
weeks.
However,
the
investigators
did
not
consider
the
RBC
cholinesterase
reduction
in
low
dose
females
to
be
biologically
significant
since
it
was
less
than
ten
percent
below
control.
The
reduction
of
brain
cholinesterase
activity
in
high
dose
male
and
female
rats
at
study
termination
was
biologically
significant."

"
No
other
changes
were
seen
in
the
test
animals
which
could
be
attributed
to
administration
of
the
test
compound.
The
increased
liver/
body
[
weight]
ratio
seen
in
high
dose
males
was
not
accompanied
by
any
body
weight
or
enzyme
changes."

The
data
presented
support
a
LOAEL
of
1.5
mg/
kg[/
day]
based
on
cholinesterase
inhibition
(
plasma
and
RBC
in
females
and
RBC
in
males).
The
NOAEL
is
0.1
mg/
kg[/
day].
A
NOAEL
of
1.5
mg/
kg/
day
may
be
defined
based
on
decreased
brain
cholinesterase
activity
in
both
sexes.

870.6100
(
82­
5)
Subchronic
Neurotoxicity
Study
in
Hens
­
MRID
43433501
CITATION:
Redgrave,
V.
(
1994)
DDVP:
28­
Day
Neurotoxicity
in
the
Domestic
Hen:
Lab
Project
Number:
AVC
1/
921405:
RAD
2/
942053.
Unpublished
study
prepared
by
Huntingdon
Research
Centre,
Ltd.
465
p.
MRID
43433501.
Page
127
of
151
EXECUTIVE
SUMMARY:
Groups
of
21
adult
domestic
hens
were
given
oral
daily
doses
by
gavage
of
0,
0.3,
1.0,
or
3.0
mg
DDVP/
kg
in
distilled
water.
Fourteen
birds
from
each
group
were
treated
for
28
days;
an
interim
sacrifice
of
6
birds/
group
was
performed
on
day
49
and
the
final
sacrifice
of
6
birds/
group
was
performed
on
day
77.
Satellite
groups
of
three
birds
from
each
original
group
of
21
were
sacrificed
on
day
4
and
day
30
for
brain
cholinesterase
and
brain
and
spinal
cord
neurotoxic
esterase
activity.
An
additional
group
of
four
birds
was
administered
0.1
mg
DDVP/
kg
for
28
days
for
cholinesterase
determination
only.
A
positive
control
group
of
21
hens
was
administered
7.5
mg
TOCP/
kg,
and
sacrificed
as
described
above.

Mortality
occurred
in
1
bird
in
the
1.0
mg/
kg
dose
group
and
in
4
birds
in
the
3.0
mg/
kg
dose
group.
Subdued
behavior,
unsteadiness,
and
vomiting
were
observed
in
the
3.0
mg/
kg
group
shortly
after
dosing
from
day
4
to
day
29.
Clinical
signs
were
also
observed
in
2
birds
after
dosing
with
1.0
mg/
kg
on
days
2
and
14.
No
delayed
motor
ataxia
was
observes,
and
there
was
no
clear
evidence
of
organophosphate
induced
delayed
neuropathy.
Decreased
body
weight
was
observed
during
the
first
14
days
of
dosing
at
1.0
and
3.0
mg/
kg,
but
compensatory
increases
occurred
from
day
14
onward.
Brain
cholinesterase
activity
was
decreased
at
day
4
in
the
1.0
mg/
kg
and
3.0
mg/
kg
dose
groups
(
44%
and
63%
decrease,
respectively,
compared
to
controls);
and,
at
day
30,
brain
cholinesterase
was
dose­
dependently
decreased
by
26%,
34%,
and
54%
in
the
0.3,
1.0,
and
3.0
mg/
kg
dose
groups,
respectively.
A
slight
increase
in
minimal
axonal
degeneration
was
observed
at
1.0
and
3.0
mg/
kg.
The
positive
control
responded
appropriately.

A
LOAEL
of
0.3
mg/
kg
can
be
defined
based
on
decreased
brain
cholinesterase
activity.
The
NOAEL
is
0.1
mg/
kg/
day.
A
NOAEL
of
0.3
mg/
kg
is
defined
based
on
axonal
degeneration
of
more
than
one
level
of
the
spinal
cord
at
1.0
mg/
kg
and
above
of
DDVP.
This
study
meets
the
guideline
requirements
of
82­
5
and
is
classified
as
Acceptable.

870.3200
(
83­
2a)
Two
Year
Gavage
Study
in
F344
Rats.
NTP
TR
342,
MRID
40299401
CITATION:
Chan,
P.
(
1987)
NTP
Technical
Report
on
the
Toxicology
and
Carcinogenesis
Studies
of
Dichlorvos
(
CAS
No.
62­
73­
7)
in
F344/
N
Rats
and
B63F1
Mice:
(
Gavage
Studies):
NTP
TR
342.
Draft
Technical
Report
of
July,
1987
prepared
for
public
review
and
comment.
US
Dept.
of
Health
and
Human
Services,
Public
Health
Service,
Publication
No.
NIH
88­
2598.
239
p.
MRID
40299401.

EXECUTIVE
SUMMARY:
In
an
oncogenicity
gavage
study
(
MRID
40299401),
4
or
8
mg/
kg/
day
dichlorvos
(
DDVP)
(
97.8­
98.2%
a.
i.,
lot
SDC­
092179,
batch
01)
in
corn
oil
(
Mazola
®
"
100%
pure")
was
administered
as
5
mL/
kg
to
60
F344
rats/
sex/
dose
5
days/
week
for
103
weeks
followed
by
a
one­
week
observation
period.
The
controls
received
corn
oil
only.
Five
rats/
sex/
dose
were
used
only
for
plasma
and
RBC
cholinesterase
(
ChE)
determination
after
6,
12,
24,
36,
52,
78,
and
104
weeks
and
5
rats/
sex/
dose
were
used
for
brain
and
sciatic
nerve
histology
at
study
termination.
The
doses
employed
were
based
on
results
of
a
13­
week
subchronic
study
where
10
rats/
sex/
dose
were
given
0,
2,
4,
8,
16,
32,
or
64
mg/
kg/
day
DDVP.
All
rats
given
32
or
64
mg/
kg/
day
and
some
rats
given
16
mg/
kg/
day
had
tremors,
diarrhea,
and
convulsions
and
died
during
the
study,
whereas
the
surviving
rats
had
no
clinical
signs
or
weight
loss.
Page
128
of
151
Mortality
and
weekly
body
weight
gains
were
similar
in
treated
and
control
animals.
Clinical
signs
among
treated
males
included
brown
fur
around
the
nose,
mouth,
and
anal
areas,
leaning
head,
and
diarrhea,
and
among
treated
females
included
vaginal
discharge,
wet
fur
in
peri­
anal
or
pelvic
area,
and
diarrhea.
From
6­
78
weeks,
plasma
ChE
levels
in
the
4
and
8
mg/
kg/
day
treated
groups
were
lower
than
the
respective
control
levels
by
52­
72%
and
53­
72%
in
males
and
by
75­
85%
and
82­
88%
in
females,
respectively.
At
104
weeks,
plasma
ChE
among
treated
groups
of
both
sexes
were
only
4­
18%
below
controls,
perhaps
due
to
the
intervening
week
without
treatment.
RBC
ChE
levels
were
more
variable:
values
were
decreased
(
13­
65%)
in
both
dose
group
females
for
weeks
6­
78
and
in
the
high­
dose
males
(
17­
90%)
for
weeks
24­
104,
but
in
the
low­
dose
males
were
decreased
(
34­
49%)
only
for
weeks
36­
78.
Treatment
time
did
not
appear
to
be
directly
related
to
ChE
inhibition.
No
gross
lesions
were
found
in
the
control
or
treated
animals.
The
incidences
of
hepatic
cytoplasmic
vacuolation,
renal
tubule
mineralization,
and
adrenal
cortical
vacuolation
were
increased
in
high­
dose
males
and
of
pancreatic
(
acinar)
atrophy
were
increased
in
high­
dose
females
(
p
 
0.05);
it
was
unclear
whether
these
effects
were
treatment­
related.
Results
of
the
brain
and
sciatic
nerve
histology
examinations
were
not
given.

Under
the
conditions
of
this
study,
4
mg/
kg/
day
was
identified
as
the
LOAEL
for
both
sexes
of
rats
based
on
decreased
RBC
and
plasma
ChE
levels.
A
NOAEL
was
not
identified.

Treatment­
related
neoplastic
lesions
were
seen
in
both
sexes
of
rats.
Males
had
an
increased
incidence
(
p
 
0.05)
of
lung
adenoma
(
8
mg/
kg/
day),
mononuclear
cell
leukemia
(
both
doses),
and
pancreatic
acinar
adenoma
(
both
doses).
Females
had
an
increased
incidence
of
mammary
gland
fibroadenoma
(
p
 
0.05
for
both
doses);
an
additional
high­
dose
female
had
mammary
gland
fibroma.

This
study
was
classified
as
"
supplementary
for
chronic
study;
minimum
for
oncogenicity"
when
the
Data
Evaluation
Report
was
originally
prepared
(
1987).
Although
this
study
did
not
follow
the
"
Subdivision
F"
guidelines
for
chronic
toxicity,
the
most
sensitive
end­
point
for
toxicity,
namely
ChE
inhibition,
was
measured
and
used
as
a
basis
for
NOAEL.
Therefore,
this
study
should
be
valid
for
performing
risk
assessment.

870.3200
(
83­
2b)
Two
Year
Gavage
Study
in
B6C3F1
Mice.
NTP
TR
342.
MRID
40299401
CITATION:
Chan,
P.
(
1987)
NTP
Technical
Report
on
the
Toxicology
and
Carcinogenesis
Studies
of
Dichlorvos
(
CAS
No.
62­
73­
7)
in
F344/
N
Rats
and
B63F1
Mice:
(
Gavage
Studies):
NTP
TR
342.
Draft
Technical
Report
of
July,
1987
prepared
for
public
review
and
comment.
US
Dept.
of
Health
and
Human
Services,
Public
Health
Service,
Publication
No.
NIH
88­
2598.
239
p.
MRID
40299401
EXECUTIVE
SUMMARY:
In
an
oncogenicity
gavage
study
(
MRID
40299401),
dichlorvos
(
DDVP)
(
97.8­
98.2%
a.
i.,
Lot
SDC­
092179,
batch
01)
in
corn
oil
(
Mazola
®
"
100%
pure")
was
administered
to
60
B6C3F1
mice/
sex/
dose
5
days/
week
for
103
weeks
followed
by
a
one­
week
observation
period.
Males
were
given
10
or
20
mg/
kg/
day
DDVP,
females
20
or
40
mg/
kg/
day
DDVP,
and
controls
corn
oil
only;
the
dosing
volume
was
10
mL/
kg.
Five
mice/
sex
dose
were
used
only
for
plasma
and
RBC
cholinesterase
(
ChE)
determination
after
6,
12,
24,
36,
52,
78,
and
104
Page
129
of
151
weeks
and
5
mice/
sex/
dose
were
used
for
brain
and
sciatic
nerve
histology
at
study
termination.
The
doses
employed
were
based
on
results
of
a
13­
week
study
where
10
mice/
sex/
dose
were
given
0,
5,
10,
20,
40,
80,
or
160
mg/
kg/
day
DDVP;
all
males
and
9
females
given
160
mg/
kg/
day
died
during
the
study.
The
survivors
had
no
dose­
related
body
weight
changes,
toxic
signs,
or
significant
pathology.

No
treatment­
related
mortality
or
body
weight
changes
were
observed,
however,
all
male
mice
used
for
ChE
determination
died
when
blood
was
withdrawn
at
24
weeks.
Reported
clinical
signs
consisted
of
a
slight
increase
of
left
pelvic
masses
in
high
dose
males
and
of
distended
abdomens
in
treated
females.
Plasma
ChE
levels
in
males
were
54­
62%
and
69­
76%
lower
than
controls
at
10
and
20
mg/
kg/
day,
respectively,
from
6­
24
weeks
(
death
of
mice
precluded
further
analysis).
Plasma
ChE
levels
in
females
were
64­
73%
and
79­
90%
lower
than
controls
at
20
and
40
mg/
kg/
day,
respectively
from
weeks
6­
78,
but
were
similar
to
or
higher
than
controls
at
week
104,
perhaps
due
to
the
intervening
week
without
treatment.
RBC
ChE
levels
were
more
variable:
levels
were
decreased
(
26­
46%)
at
week
24
in
both
sexes
and
by
11­
33%
at
weeks
36,
52,
and
104
in
females,
but
were
similar
to
or
greater
than
controls
at
weeks
6
and
12
(
both
sexes,
both
doses)
and
78
(
females,
both
doses).
Treatment
time
did
not
appear
to
be
directly
related
to
ChE
inhibition.
No
treatment­
related
gross
or
microscopic
lesions
were
found
and
no
lesions
were
seen
in
the
animals
used
to
investigate
brain
and
sciatic
nerve
histology.
Under
the
conditions
of
this
study,
a
LOAEL
of
10
mg/
kg/
day
was
identified
based
on
the
decreased
RBC
and
plasma
ChE
levels
in
males.
A
NOAEL
was
not
identified.

The
incidence
of
forestomach
squamous
cell
papilloma
was
increased
in
high
dose
males
(
5/
50
vs.
1/
50
for
controls,
p
=
0.06)
and
females
(
18/
50
vs.
5/
50
for
controls,
p
 
0.05);
forestomach
carcinoma
also
occurred
in
2/
50
high­
dose
females.
Three
high­
dose
males
each
had
one
unusual
neoplasm:
glandular
stomach
carcinoid/
carcinoma,
duodenal
adenocarcinoma,
or
a
duodenal
adenomatous
polyp.

This
oncogenicity
study
was
classified
as
"
core­
minimum"
when
the
Data
Evaluation
Report
was
originally
prepared
(
1987).

870.4200
(
83­
2)
80­
Week
Feeding/
Carcinogenicity
study
in
Rats
­
TXR007765,
NCI,
1977
EXECUTIVE
SUMMARY:
In
an
80­
week
feeding/
carcinogenicity
study
(
NCI,
1977),
groups
of
fifty
36­
43
day
old
Osborne­
Mendel
rats/
sex
were
administered
DDVP
(
94%)
at
dose
levels
(
timeweighted
average)
of
150
or
326
ppm
(
7.5
and
16.3
mg/
kg/
day
by
standard
convention
methods).
The
dosage
for
the
high­
dose
group
was
1000
ppm
(
50
mg/
kg/
day)
for
the
first
3
weeks
and
was
then
changed
to
300
ppm
(
15
mg/
kg/
day)
for
the
remaining
77
weeks
due
to
toxicity.
A
matched
control
group
of
10
rats/
sex
was
included.
The
pooled
control
group
consisted
of
60
male
and
60
female
rats.
All
animals
were
observed
twice
daily
for
signs
of
toxicity,
weighed
at
regular
intervals,
and
palpated
for
masses
at
each
weighing.
Gross
and
microscopic
examination
of
all
major
tissues,
organs
and
gross
lesions
were
made
from
sacrificed
animals,
and
where
feasible,
from
animals
found
dead.
Rats
were
sacrificed
at
110­
111
weeks.
Page
130
of
151
Severe
signs
of
toxicity
including
tremors,
rough
hair
coat,
diarrhea
and
poor
appearance
were
observed
in
the
1000
ppm
DDVP
group
during
the
first
3
weeks.
All
groups
showed
slight
or
moderate
degrees
of
toxicity
during
the
first
year.
Treated
animals
showed
an
increased
frequency
of
toxic
signs
during
the
second
year
consisting
of
rough
hair
coats,
epistaxis,
hematuria,
alopecia,
dark
urine,
bloating
and
abdominal
distension.
No
compound­
related
mortality
was
reported.
Survival
was
64%
and
76%
in
males
in
the
low­
and
high­
dose
groups,
respectively,
for
over
105
weeks.
Survival
was
80%
and
84%
in
females
in
the
low­
and
high­
dose
groups,
respectively,
for
over
105
weeks.
During
the
first
year
and
a
half,
body
weights
of
male
and
female
rats
in
the
highdose
group
were
consistently
lower
than
the
low­
dose
and
matched
control
groups.
Thyroid
follicular
hyperplasia
was
increased
in
males
in
the
low­
dose
group
(
7%)
and
high­
dose
group
(
10%)
when
compared
to
controls
(
0%).
The
incidence
of
alveolar
macrophages
was
increased
in
treated
males
(
14­
28%)
and
treated
females
(
42­
44%)
when
compared
to
controls
(
0­
10%).
The
incidence
of
interstitial
fibrosis
of
the
myocardium
was
increased
in
treated
males
(
24­
32%)
and
treated
females
(
30­
38%)
when
compared
to
controls
(
10%).
Malignant
fibrous
histiocytoma
was
increased
in
male
rats
in
the
low­
dose
group
(
8%)
and
high­
dose
group
(
16%)
when
compared
to
pooled
controls
(
3%,
linear
trend
p=
0.018).
This
neoplasm
occurred
in
10%
of
the
matched
controls.
Under
the
conditions
of
the
study,
DDVP
was
not
demonstrated
to
be
carcinogenic
in
rats.

The
study
is
Unacceptable­
Guideline
and
does
not
satisfy
the
guideline
requirement
(
series
83­
2)
for
a
carcinogenicity
study
in
rats.
Too
few
animals
(
10/
sex)
were
used
as
matched
controls
and
only
2
dose
levels
were
employed.

870.4200
(
83­
2)
94­
Week
Feeding/
Carcinogenicity
Study
in
B6C3F1
Mice
­
TXR
007765,
NCI,
1977
EXECUTIVE
SUMMARY:
In
a
94­
week
feeding/
carcinogenicity
study
(
NCI,
1977),
groups
of
fifty
B6C3F1
mice/
sex,
35­
36
days
of
age,
were
administered
DDVP
(
94%)
at
dose
levels
(
timeweighted
average)
of
318
or
635
ppm
(
47.7
and
95.3
mg/
kg/
day
by
standard
convention
methods).
The
dosage
levels
for
the
low­
and
high­
dose
mice
were
1000
and
2000
ppm
(
150
and
300
mg/
kg/
day)
for
the
first
2
weeks,
then
reduced
to
300
and
600
ppm
(
45
and
90
mg/
kg/
day)
for
the
remaining
78
weeks.
A
matched
control
group
of
10
mice/
sex
was
included.
The
pooled
control
group
consisted
of
100
males
and
80
females.
All
animals
were
examined
twice
daily
for
signs
of
toxicity,
weighed
at
regular
intervals,
and
palpated
for
masses
at
each
weighing.
Gross
and
microscopic
examination
of
all
major
tissues,
organs
and
gross
lesions
were
made
from
sacrificed
animals
and,
where
feasible,
from
animals
found
dead.
The
mice
were
sacrificed
at
92­
94
weeks.

Initially,
mice
fed
DDVP
exhibited
severe
signs
of
toxicity:
tremors,
rough
coat,
diarrhea
and
poor
general
appearance.
After
doses
were
reduced,
the
behavior
and
appearance
of
treated
mice
were
comparable
to
controls.
Survival
was
92%
and
90%
in
males
in
the
low­
and
high­
dose
groups,
respectively.
Survival
was
74%
and
84%
in
females
in
the
low­
and
high­
dose
groups,
respectively.
The
body
weight
of
male
and
female
mice
in
the
high­
dose
group
was
generally
lower
after
the
initial
growth
phase
than
the
low­
dose
and
control
groups.
Two
squamous­
cell
carcinomas
of
the
esophageal
epithelium
occurred,
1
in
a
low­
dose
male
and
1
in
a
high­
dose
female.
Two
low­
dose
males
had
focal
hyperplasia
of
the
esophageal
epithelium.
And
one
high­
dose
female
had
a
papilloma
of
the
esophageal
epithelium.
There
was
insufficient
information
to
establish
the
association
of
Page
131
of
151
esophageal
tumors
with
DDVP
treatment.
Under
the
conditions
of
the
study,
DDVP
was
not
demonstrated
to
be
carcinogenic
in
mice.

The
study
is
Unacceptable­
Guideline
and
does
not
satisfy
the
guideline
requirement
(
series
83­
2)
for
a
carcinogenicity
study
in
mice.
Too
few
animals
(
10/
sex)
were
used
as
matched
controls
and
only
two
dose
levels
were
employed.

870.4100
(
83­
1b)
52­
Week
Chronic
Oral
Toxicity
Study
in
Dogs.
MRID
41593101
CITATION:
Markiewicz,
V.
(
1990)
A
52­
Week
Chronic
Toxicity
Study
on
DDVP
in
Dogs:
Lab
Project
Number:
2534/
102.
Unpublished
study
prepared
by
Hazleton
Laboratories
America,
Inc.
431
p.
MRID
41593101
EXECUTIVE
SUMMARY:
In
a
chronic
oral
toxicity
study
(
MRID
41593101),
dichlorvos
(
DDVP)
(
purity
not
given
but
was
97.3%
in
the
preceding
range
finding
study;
Lot
No.
802097)
was
administered
to
4
beagle
dogs/
sex/
dose
by
capsule
for
52
weeks
at
doses
of
0,
0.1,
1.0,
or
3.0
mg/
kg/
day.
Due
to
excessive
plasma
cholinesterase
inhibition
at
week
2,
the
low
dose
was
changed
from
0.1
to
0.05
mg/
kg/
day
in
both
sexes
on
treatment
day
22
to
achieve
a
NOAEL.

No
dogs
died
during
the
study.
Clinical
signs
included
ataxia,
salivation,
and
dyspnea
in
one
highdose
male
on
one
day
during
week
33
and
emesis
in
three
high­
dose
females
and
one
male
and/
or
female
at
most
other
doses.
Cumulative
body
weight
gains
were
lower
than
that
of
controls
only
in
the
high­
dose
males,
from
approximately
weeks
1­
8.
No
treatment­
related
effects
were
noted
on
the
food
consumption,
ophthalmoscopic
examination,
hematology,
urinalysis,
gross
or
microscopic
pathology,
organ
weights,
or
clinical
chemistry
except
for
cholinesterase
(
ChE)
measurements.
After
2
weeks
of
treatment,
plasma
ChE
levels
were
21­
26%
lower
than
pretreatment
values
for
both
sexes
given
0.1
mg/
kg/
day
DDVP,
prompting
the
dose
decrease
to
0.05
mg/
kg/
day
on
day
22.
At
subsequent
test
weeks
(
6,
13,
26,
39,
and
52),
plasma
ChE
levels
in
the
low­
dose
group
were
within
12%
of
pretreatment
values.
Plasma
ChE
levels
of
dogs
given
1.0
and
3.0
mg/
kg/
day
DDVP
were
decreased
39­
59%
and
61­
74%,
respectively,
throughout
the
study
in
both
sexes.
RBC
ChE
levels
were
decreased
in
low­
dose
dogs
at
week
6
(
24%
in
males
and
50%
in
females),
likely
due
to
effects
of
the
earlier
higher
dose
of
0.1
mg/
kg/
day,
but
were
within
13%
of
pretreatment
values
at
all
other
time
points.
At
1.0
or
3.0
mg/
kg/
day
DDVP,
RBC
ChE
levels
in
both
sexes
were
lowered
33­
65%
and
67­
94%,
respectively,
throughout
the
study.
The
%
inhibition
of
neither
plasma
nor
RBC
ChE
appeared
to
change
with
time.
Brain
ChE
measurements
taken
at
termination
were
comparable
to
concurrent
controls
for
the
low
dose
groups
but
were
decreased
at
both
1.0
mg/
kg/
day
(
22%,
p
 
0.05
in
males;
7%,
N.
S.
in
females)
and
3.0
mg/
kg/
day
(
47%
in
males
and
29%
in
females,
p
 
0.05
for
both).

Under
the
conditions
of
this
study,
the
NOAEL
was
identified
as
0.05
mg/
kg/
day
for
both
sexes.
The
L0EL
was
1.0
mg/
kg/
day,
based
on
the
inhibition
of
plasma
and
RBC
ChE
levels
in
both
sexes
and
the
inhibition
of
brain
ChE
in
males.
It
should
be
noted
that
the
actual
LOAEL
could
be
as
low
as
0.1
mg/
kg/
day
since
plasma
ChE
was
decreased
by
nearly
25%
after
the
initial
administration
of
this
dose
to
the
low­
dose
group
during
the
first
two
weeks.
Page
132
of
151
This
study
was
classified
as
acceptable
(
guideline)
for
satisfying
the
guideline
requirement
for
a
chronic
oral
toxicity
study
(
83­
1b)
in
dogs.

870.3700
(
83­
3a)
Developmental
Oral
Toxicity
Study
in
SD
Rats.

CITATION:
Tyl,
R.;
Marr,
M.;
Myers,
C.
(
1991)
Developmental
Toxicity
Evaluation
of
DDVP
Administered
by
Gavage
to
CD
(
Sprague­
Dawley)
Rats:
Lab
Project
Number:
60C­
4629­
10/
20.
Unpublished
study
prepared
by
Research
Triangle
Inst.
305
p.
MRID
41951501
EXECUTIVE
SUMMARY:
In
a
developmental
toxicity
study
(
MRID
41951501),
25
pregnant
Sprague­
Dawley
rats
per
group
were
administered
Dichlorvos
(
96.86%
a.
i.;
Lot
No.
802097)
by
gavage
at
doses
of
0,
0.1,
3.0,
or
21.0
mg/
kg/
day
on
gestation
days
(
GD)
6­
15,
inclusive.
On
GD
20,
all
dams
were
sacrificed
and
all
fetuses
were
examined
for
external
anomalies.
Approximately
one­
half
of
all
fetuses
were
examined
for
visceral
anomalies
and
the
remainder
stained
and
examined
for
skeletal
anomalies.

All
animals
survived
until
scheduled
sacrifice.
There
was
no
evidence
of
maternal
toxicity
at
0.1
or
3.0
mg/
kg/
day.
At
the
high
dose,
clinical
signs
of
toxicity
were
indicative
of
cholinesterase
inhibition.
All
high­
dose
dams
exhibited
tremors
at
some
time
during
the
dosing
period.
Other
anticholinesterase­
related
signs
of
toxicity
included
prone
positioning,
hindlimb
splay,
circling,
vocalization,
excitability,
hypoactivity,
and
labored
respiration
among
others.

Absolute
maternal
body
weights
of
the
high­
dose
dams
were
significantly
(
4­
6%;
p
 
0.05)
lower
than
the
controls
on
GD
9,
12,
and
15
and
body
weight
gains
during
the
dosing
period
were
significantly
(
p
 
0.01)
decreased
by
28%.
Food
consumption
and
food
efficiency
of
high­
dose
dams
were
significantly
(
p
 
0.01)
less
than
the
controls
during
the
dosing
interval
and
overall
(
GD
0­
20).

Therefore,
the
maternal
toxicity
LOAEL
is
21
mg/
kg/
day
based
on
clinical
signs
of
toxicity,
reduced
body
weight
gain,
and
food
consumption
and
efficiency.
The
maternal
toxicity
NOAEL
is
3
mg/
kg/
day.

No
treatment­
related
effects
were
observed
for
gravid
uterine
weights,
number
of
fetuses/
litter,
preand
post­
implantation
loss,
numbers
of
corpora
lutea/
dam,
number
of
implantations/
dam,
resorptions/
dam,
fetal
body
weights,
or
fetal
sex
ratios.
There
were
no
developmental
malformations/
variations
in
any
fetus
that
were
attributed
to
treatment.

Therefore,
the
developmental
toxicity
NOAEL
is
 
21
mg/
kg/
day
and
the
developmental
toxicity
LOAEL
was
not
identified.

This
study
is
classified
as
Acceptable
(
guideline)
and
satisfies
the
guideline
requirements
for
a
developmental
toxicity
study
(
83­
3a)
in
rats.

870.3700
(
83­
3b)
Developmental
Oral
Toxicity
Study
in
New
Zealand
Rabbits.
Page
133
of
151
CITATION:
Tyl,
R.;
Marr,
M.;
Myers,
C.
(
1991)
Development
Toxicity
Evaluation
of
DDVP
Administered
by
Gavage
to
New
Zealand
White
Rabbits:
Lab
Project
Number:
60C­
4629­
30/
40.
Unpublished
study
prepared
by
Research
Triangle
Institute.
247
p.
MRID
No.
41802401
EXECUTIVE
SUMMARY:
In
a
developmental
(
teratology)
toxicity
study
(
MRID
41802401),
16
pregnant
New
Zealand
rabbits
per
group
were
administered
Dichlorvos
(
97%
purity;
Lot
No.
802097)
by
gavage
at
doses
0,
0.1,
2.5,
or
7.0
mg/
kg/
day
on
gestation
days
(
GD)
7­
19.
(
Dose
selection
was
based
on
a
range­
finding
study
in
which
maternal
toxicity,
including
increased
mortality
(
5/
8
died),
decreased
weight
gain,
and
clinical
signs,
were
manifested
at
the
highest
tested
dose
of
10
mg/
kg/
day.)
At
study
termination
(
GD
30),
the
number
of
does
with
live
fetuses
was
14,
12,
11,
and
9
in
each
of
the
control,
0.1,
2.5,
and
7.0
mg/
kg/
day
group,
respectively.
On
GD
30,
all
surviving
dams
were
euthanized
and
all
fetuses
were
weighed
and
examined
for
external,
skeletal,
and
visceral
anomalies.

Maternal
toxicity
(
dose­
dependent)
was
evident
in
the
form
of
dose­
dependent
increased
mortality
(
four
and
two
died
in
the
high
and
mid­
dose
groups,
respectively),
decreased
mean
body
weight
gain
and
typical
anticholinesterase­
related
clinical
observations.
Mean
body
weight
gain
during
the
dosing
period
(
GD
7­
19)
was
67%
and
58%
below
control
in
the
mid
and
high
dose
groups,
respectively.
Mean
body
weight
gain
during
the
entire
gestation
period
(
corrected
for
gravid
uterine
weight)
was
variable
where,
compared
to
the
control
group,
it
was
higher
in
the
low
and
mid
dose
groups
(
by
140%
and
45%,
respectively)
and
lower
(
54%,
p<
0.05)
in
the
high
dose
group.
There
were
no
abortions
but
two
does
in
the
low­
dose
group
had
premature
deliveries
(
GD
23
and
30).

Therefore,
based
on
mortality,
and
other
effects,
the
maternal
toxicity
LOAEL
is
7.0
mg/
kg/
day;
the
maternal
toxicity
NOAEL
is
2.5
mg/
kg/
day.
There
were
no
statistically
significant
treatment­
related
differences
in
the
number
(
per
doe)
of
corpora
lutea,
implantations,
live
fetuses,
resorptions,
or
dead
fetuses.
Though
not
indicated
to
be
significantly
different
than
the
control
group,
the
low­
dose
group
had
fewer
implantations/
doe
(
4.9
±
0.8
vs.
7.0
±
0.8)
and
fewer
live
fetuses/
doe
(
4.8
±
0.8
vs.
6.5
±
0.8).
There
were
no
apparent
developmental
malformations
or
variations
that
could
be
attributed
to
treatment.

Therefore,
the
developmental
toxicity
NOAEL
is
>
7
mg/
kg/
day
and
the
developmental
toxicity
LOAEL
was
not
identified.

This
study
was
classified
as
Core
Minimum
where
all
criteria
were
satisfied
except
for
the
minimum
number
(
12)
of
available
does/
group
which,
due
to
mortality
in
the
mid
and
high
dose
groups,
were
11
and
9,
respectively.
The
reviewer
of
this
study
also
indicated
that
individual
data
on
corpora
lutea
were
not
submitted.

870.3800
(
83­
4)
Two­
Generation
Reproduction
Study
in
SD
Rats.
MRID
No.
42483901
CITATION:
Tyl,
R.;
Myers,
C.;
Marr,
M.
(
1992)
Two­
Generation
Reproductive
Toxicity
Study
of
DDVP
Administered
in
Drinking
Water
to
CD
(
Sprague­
Dawley)
Page
134
of
151
Rats:
Final
Report:
Lab
Project
Number
60C­
4629­
170.
Unpublished
study
prepared
by
Research
Triangle
Institute.
1225
p.
MRID
No.
42483901
EXECUTIVE
SUMMARY:
In
a
2­
generation
reproduction
study
(
MRID
42483901)
DDVP
(
96.86%)
was
administered
to
30
CD
(
Sprague­
Dawley)
rats/
sex/
dose
in
their
drinking
water
at
concentrations
of
0,
5,
20
and
80
ppm.
Equivalent
dosages
were
the
following:

Table
10.

Water
Conc.
(
ppm)
F0
&
F1
 
(
µ
g/
kg/
day)
F0
&
F1
 
prebreeding
(
µ
g/
kg/
day)
F0
&
F1
 
gestation
(
µ
g/
kg/
day)
F0
&
F1
 
lactation
(
µ
g/
kg/
day)

5.0
476­
500
650­
660
564­
590
930­
1176
20.0
1923­
1952
2432­
2673
2124­
2420
4280­
4596
80.0
6897­
7528
9370­
9472
7035­
8150
13238­
17468
After
at
least
10
weeks
of
continuous
exposure,
rats
were
randomly
mated
within
treatment
groups
to
produce
the
F1
generation;
after
mating
the
F0
males
were
necropsied.
F1
litters
were
culled
to
8
pups
(
4
 
,
4
 
when
possible)
on
post
natal
day
8
and
weaned
on
day
21.
Ten
weanlings/
sex/
dose
were
necropsied
and
30
weanlings/
sex/
dose
were
selected
as
F1
parents
with
at
least
11­
week
prebreeding
exposure
to
DDVP
in
their
water.
These
rats
were
about
14­
17
weeks
old
when
mated
and
their
F2(
a)
litters
were
culled
to
8
pups/
litter
on
post
natal
day
8.
At
weaning,
10
F2(
a)
weanlings/
sex/
dose
level
were
necropsied.

Due
to
poor
reproductive
performance
(
not
treatment
or
dose­
related),
F1
females
were
evaluated
for
vaginal
estrus
cyclicity
and
then
rebred
with
untreated
males
to
produce
F2(
b)
litters
which
were
culled
on
PND
8
(
8
pups/
litter)
and
necropsied
(
10/
sex/
dose)
after
weaning.

Systemic
toxicity:
A
NOAEL
for
cholinesterase
inhibition
in
parental
animals
was
not
observed.
Cholinesterase
levels
were
dose­
dependently
decreased
in
plasma
(
by
3.6
to
57.4%),
erythrocytes
(
by
7.0
to
60.5%),
and
brain
(
by
1.1
to
60.3%)
from
F0
and
F1
animals
and,
overall,
females
were
more
sensitive
than
males.
No
ChE
measurements
were
done
on
the
F2(
a)
or
F2(
b)
progeny.
Water
consumption
was
also
reduced
in
the
80
ppm
dosed
animals.

Reproductive
toxicity:
No
effects
on
reproductive
parameters
were
observed
in
the
F0
mating,
although
mean
pup
body
weight
in
the
80
ppm
group
at
weaning
(
day
21)
was
significantly
lower
than
controls
(
57.02
vs.
62.29
g).
In
the
first
mating
of
the
F1
animals,
incidences
of
pregnancies
were
low
(
controls:
17/
30;
5
ppm:
14/
30;
20
ppm:
16/
30;
80
ppm:
11/
30).
Mean
pup
body
weight
in
the
80
ppm
group
at
weaning
was
noticeably
(
not
significantly)
lower
than
controls
(
52.22
vs.
57.43
g).
As
stated
in
the
report
conclusions:
"
Parental
reproductive
parameters
were
slightly
affected
in
F1
animals
at
80
ppm,
although
these
changes
did
not
achieve
statistical
significance.
Offspring
survival
was
also
slightly
reduced
at
80
ppm,
associated
with
accompanying
maternal
toxicity
seen
at
this
dose
level."
Page
135
of
151
Results
of
the
estrous
cyclicity
assessment
showed
that
in
the
80
ppm
F1
group,
there
was
a
statistically
significant
decrease
in
the
percent
of
females
cycling
(
63.3%,
control
86.2%)
accompanied
by
increased
abnormal
cycling
(
68.4%,
control
16%).

In
the
F2(
b)
mating,
incidences
of
pregnancies
were
still
relatively
low
(
controls:
19/
29;
5
ppm:
19/
30;
20
ppm:
17/
30;
80
ppm:
13/
30);
in
terms
of
pregnancies/
confirmed
copulations
incidences
were:
controls:
19/
25
(
76%);
5
ppm:
19/
27
(
70.4%);
20
ppm:
17/
27
(
63%);
80
ppm:
13/
26
(
50%).

The
LOAEL
for
systemic
toxicity
[
drinking
water
administration]
is
5
ppm
(
488
µ
g/
kg/
day
in
males,
577
µ
g/
kg/
day
in
females),
based
on
RBC
and
plasma
cholinesterase
inhibition.
The
NOAEL
is
<
5
ppm
(<
488
µ
g/
kg/
day
in
males,
<
577
µ
g/
kg/
day
in
females).

The
reproductive
LOAEL
[
drinking
water
administration]
is
80
ppm
(
7592
µ
g/
kg/
day)
based
on
the
lack
of
cycling
and
abnormal
cycling
due
to
persistent
or
prolonged
estrus.
In
addition,
parental
reproductive
parameters
(
decreased
pregnancy
and
fertility,
and
decreased
live
litters
and
survival)
were
slightly
affected
in
F1
animals
at
80
ppm,
although
these
changes
did
not
achieve
statistical
significance.
Offspring
survival
was
also
slightly
reduced.
The
reproductive
NOAEL
is
20
ppm
(
4438
µ
g/
kg/
day).

81­
8ss
Acute
Oral
Neurotoxicity
Study
in
Rats.

CITATION:
Lamb,
I.
(
1993)
An
Acute
Neurotoxicity
Study
of
Dichlorvos
in
Rats:
Final
Report
(
Text
and
Summary
Data):
Lab
Project
Number:
WIL­
188003.
Unpublished
study
prepared
by
WIL
Research
Labs.,
Inc.
984
p.
MRID
42655301
EXECUTIVE
SUMMARY:
In
an
acute
oral
neurotoxicity
study
(
MRID
42655301),
a
single
gavage
dose
of
dichlorvos
(
97.8%
a.
i.,
lot
#
80209)
was
administered
in
deionized
water
to
12
Sprague­
Dawley
rats/
sex/
group
at
0,
0.5,
35,
or
70
mg/
kg.
The
animals
were
observed
for
up
to
14
days.
Functional
Observational
Battery
(
FOB)
tests
were
done
pretest
and
on
study
days
0
(
15
minutes
after
compound
administration),
7
and
14.
Animals
surviving
to
study
termination
were
sacrificed
and
perfused
in
situ
for
neurohistopathological
evaluation.
All
animals
were
necropsied.

Two
high­
dose
males
and
five
high­
dose
females
died
within
four
hours
of
compound
administration.
All
other
animals
survived
until
study
termination.
No
body
weight
effects
were
observed.
The
FOB
and
motor
activity
effects
(
described
below)
of
dichlorvos
were
most
prevalent
10­
20
minutes
post­
dosing
and
had
essentially
resolved
by
days
7
and
14.
Statistically
significant
(
p<
0.05)
postural
alterations,
tremors,
salivation,
and
changes
in
fur
appearance
and
skin
color
were
observed
in
midand
high­
dose
males
and
females.
High­
dose
males
exhibited
an
increased
incidence
(
p<
0.05)
of
exophthalmus.
Group
mean
time
to
first
step
was
significantly
(
p<
0.01)
increased
in
high­
dose
males
(
31.7
sec)
and
females
(
18.3
sec).
Treatment­
related
(
p<
0.05)
decreased
group
mean
rearing,
impaired
mobility,
abnormal
gait,
and
decreased
arousal
level
were
also
observed
in
mid­
and
highdose
males
and
females.
Dose­
related
(
p<
0.05)
alterations
of
touch,
tail
pinch,
pupil
response
and
air
righting
reflex
were
observed
in
mid­
and
high­
dose
males
and
in
high­
dose
females.
Dose
Page
136
of
151
related
decreased
hindlimb
resistance
(
mid­
and
high­
dose,
p<
0.05),
grip
strength
(
high­
dose,
p<
0.01),
and
rotarod
performance
(
mid­
and
high­
dose,
p<
0.01)
were
observed
in
male
and
female
rats.
Decreased
(
p<
0.01)
mean
body
temperature
was
observed
in
mid­
and
high­
dose
males
and
females,
and
increased
(
p<
0.01)
group
mean
catalepsy
values
were
observed
in
high­
dose
animals
of
both
sexes.
No
brain
weight,
brain
dimension,
or
neurohistopathological
effects
were
observed.

Under
the
conditions
of
this
study,
the
LOAEL
for
dichlorvos
is
35
mg/
kg
and
the
NOAEL
is
0.5
mg/
kg
based
on
changes
in
the
FOB,
decreased
motor
activity,
and
decreased
body
temperature.
This
study
is
classified
as
acceptable
(
guideline)
for
an
acute
neurotoxicity
study
in
rats
(
81­
8ss).

81­
8ss
Subchronic
Oral
Neurotoxicity
Study
in
Rats.

CITATION:
Lamb,
I.
(
1993)
A
Subchronic
(
13
Week)
Neurotoxicity
Study
of
Dichlorvos
in
Rats:
Final
Report:
Lab
Project
Number:
WIL­
188004.
Unpublished
study
prepared
by
WIL
Research
Labs,
Inc.
1199
p.
MRID
42958101.

EXECUTIVE
SUMMARY:
In
a
subchronic
oral
neurotoxicity
study
(
MRID
42958101),
dichlorvos
(
97.87%
a.
i.,
lot
No.
802097)
was
administered
in
deionized
water
to
15
Sprague­
Dawley
rats/
sex/
group
at
gavage
doses
of
0,
0.1,
7.5,
or
15.0
mg/
kg/
day
for
90
days.
Within
each
dose
group,
10
rats/
sex
were
allocated
for
brain
cholinesterase
determination
and
5
rats/
sex
were
allocated
for
neuropathology
evaluation.
Additionally,
blood
samples
were
collected
for
cholinesterase
measurements
prestudy
and
on
study
weeks
3,
7,
and
13.
Five
rats/
sex/
dose
from
the
cholinesterase
group
and
5/
sex/
dose
from
the
neuropathology
group
were
evaluated
with
the
Functional
Observational
Battery
(
FOB)
and
motor
activity
tests
pretest
and
on
study
weeks
3,
7,
and
12.
Body
weight
and
food
consumption
were
measured
weekly.

There
was
no
treatment­
related
mortality.
Mean
body
weight
in
high­
dose
females
was
consistently
lower
than
the
control
(
11­
21%)
throughout
the
study.
No
body
weight
effects
were
observed
in
any
other
animals,
and
there
was
no
treatment­
related
effect
on
food
consumption.
Tremors,
salivation,
exophthalmos,
lacrimation,
and
clear
material
on
the
forelimbs
were
observed
in
high­
dose
males
and
females
approximately
15
minutes
post­
dosing.
Rales,
chromodacryorrhea,
and
red/
yellow/
orange
material
around
the
nose
and
mouth
were
also
seen
in
high­
dose
rats.
Tremors
were
observed
in
three
mid­
dose
males
and
nine
mid­
dose
females.
Generally,
the
clinical
signs
occurred
during
the
third
week
of
treatment
in
the
mid­
dose
animals,
and
as
early
as
the
first
week
of
dosing
and
throughout
the
study
in
the
high­
dose
rats.
Cholinesterase
activity
was
decreased
in
midand
high­
dose
male
and
female
rats
as
follows:
plasma
30­
58%;
erythrocyte
8­
35%;
brainstem
and
brain
cortex
10­
16%.
There
were
no
treatment­
related
effects
in
the
FOB
or
motor
activity
tests.
No
treatment­
related
neurohistopathological
lesions
and
no
apparent
changes
in
brain
weight
or
size
were
observed.

Based
on
decreased
cholinesterase
activity
and
clinical
cholinergic
signs,
the
LOAEL
for
dichlorvos
is
7.50
mg/
kg
and
the
NOAEL
is
0.1
mg/
kg.
This
study
is
classified
as
acceptable
(
guideline)
for
a
subchronic
neurotoxicity
study
in
rats
(
81­
8ss).
Page
137
of
151
g.
Mutagenicity
Mutagenicity
Studies
with
Positive
Results
Several
in
vitro
and
in
vivo
mutagenicity
studies
were
reviewed
and
presented
to
the
Cancer
Peer
Review
Committee
(
CPRC)
by
Kerry
Deerfield
in
a
Memorandum
entitled,
"
Review
of
the
in
vivo
mutagenicity
studies
concerning
Dichlorvos"
(
dated
August
10,
1988).
Another
review
may
be
found
in
the
more
recent
Memorandum
entitled,
"
Fifth
carcinogenicity
peer
review
of
Dichlorvos"
by
Jocelyn
Stewart
(
dated
August
28,
1996).
Though
lacking
sufficient
detail,
these
two
reviews
provide
some
information
about
the
types
and
variety
of
mutagenicity/
genotoxicity
studies
that
were
considered
by
the
Agency
since
DDVP
has
been
registered.

DDVP
has
been
shown
to
be
a
direct
acting
mutagen
by
common
in
vitro
bacterial
genetic
toxicity
assays.
For
instance,
DDVP
is
mutagenic
in
the
base­
substitution
Salmonella
strain,
TA100
as
well
as
in
the
E.
coli
WP2
mutation
assay
(
Moriya
et
al.,
1983).
In
this
study,
238
pesticides
including
DDVP
were
tested
by
the
Ames
plate
incorporation
method
in
five
Salmonella
strains
(
TA1535,
TA100,
TA1537,
TA1538,
and
TA98)
as
well
as
in
E.
Coli
(
WP2
hcr)
both
in
the
presence
or
absence
of
an
S­
9
metabolizing
system.
DDVP
(
technical,
unknown
purity)
was
added
(
0.1
mL
in
DMSO)
at
0,
100,
500,
1,000,
5,000
or
10,000
µ
g/
plate
and
all
plates
were
incubated
for
two
days
at
37
°
C
prior
to
counting
revertant
colonies.
In
Salmonella
TA100,
DDVP
gave
rise
to
a
dosedependent
response
from
100
to
5000
µ
g/
plate
with
a
maximum
increased
mutation
of
nearly
4.5­
fold
over
control
in
the
absence
of
S­
9
activation
while
complete
toxicity
was
seen
at
the
highest
dose
tested.
Addition
of
S­
9
metabolizing
system
reduced
the
mutation
frequency
to
a
maximum
of
nearly
2­
fold
(
at
5000
µ
g/
plate)
over
background.
DDVP
was
also
positive
in
E.
coli
WP2
hcr,
though
no
actual
data
were
provided.
The
other
tested
strains
failed
to
respond
to
DDVP
in
the
presence
or
absence
of
S­
9
activation.
Therefore,
DDVP
was
shown
to
be
a
direct
acting
mutagen
in
TA100
(
and
in
E.
coli
WP2
hcr)
where,
compared
to
44
other
direct
acting
mutagens
in
the
same
study,
DDVP
ranked
26
with
a
mutagenic
potency
of
0.027
revertants/
nmole
(
most
and
least
potent
were
Captan
in
TA100
and
ETU
in
TA1535
scoring
93.7
and
0.00065
revertants/
nmole,
respectively)
(
Moriya
et
al.,
1983).

A
single
dose
of
apparently
5000
µ
g
DDVP
(>
97%
a.
i.)
in
cultures
of
E.
coli
(
B/
r
WP2
and
WP2
hcr)
and
in
S.
typhimurium
(
TA1535
and
TA1538)
was
tested
with
or
without
S­
9
metabolic
activation.
(
According
to
HED
doc.
#
007765,
p.
143,
0.1
mL
of
pesticide
solution
containing
22.6
µ
M
DDVP
was
used.
However,
the
author
of
this
document
interprets
this
to
mean
that
22.6
µ
moles,
equaling
5000
µ
g,
of
DDVP
in
0.1
mL
solution
was
used;
otherwise,
the
amount
of
DDVP
in
0.1
mL
of
the
22.6
µ
M
solution
would
be
only
0.5
µ
g.)
Water
served
as
negative
(
solvent)
control.
In
the
absence
of
S­
9
activation,
DDVP
was
positive
in
both
the
E.
coli
and
TA1535
strains
(
10­
30
fold
increased
revertants
above
background).
S­
9
metabolic
activation
abolished
DDVP's
mutagenicity
in
TA1535
but
not
in
E.
coli
(
Moriya
et
al.,
1978).
This
study
was
considered
acceptable
despite
using
one
dose
only
and
no
reporting
of
concurrent
control
values
(
HED
doc.
#
007765).

Positive
mutation
findings
were
also
reported
in
two
E.
coli
WP2
strains
(
trp­
and
the
plasmidcontaining
CM881)
in
another
study
which
only
tested
DDVP
(
a.
i.
not
specified)
at
concentrations
from
0.1
µ
g/
mL
(
in
the
agar
incorporation
method)
to
2000
µ
g/
mL
(
in
the
treat
and
plate
method)
in
Page
138
of
151
the
absence
of
S­
9
metabolic
activation.
DDVP
induced
reversion
by
base
substitution
in
both
the
agar
(
5
µ
g/
mL
agar)
or
the
standard
treat
and
plate
method
(
2000
µ
g/
mL)
(
Bridges,
1978).
This
study
was
judged
inconclusive
as
a
comprehensive
test
of
mutagenicity
because
it
was
not
also
performed
with
mammalian
metabolic
activation
(
HED
doc.
#
007765).

An
earlier
study
screened
11
S.
typhimurium
histidine­
requiring
strains
and
seven
E.
coli
tryptophanrequiring
strains
by
spot
testing
DDVP
(%
a.
i.
not
specified)
and
139
other
organophosphorus
compounds
by
adding
5­
10
µ
l
of
each
chemical
to
each
bacterial
strain
and
counting
revertants
compared
to
controls
after
48
and
72
hr
incubation
at
37
°
C.
Results
were
represented
qualitatively
using
+/­
designation.
DDVP
was
positive
(+)
in
strains
that
were
designed
to
detect
base­
pair
substitution
mutagens
(
such
as
TA1530,
TA1535,
WP2,
uvrA,
and
WP67)
but
was
negative
(­)
in
strains
that
detect
frame­
shift
mutagens
(
e.
g.,
TA1536,
TA1537,
and
TA1538)
(
Hanna
and
Dyer,
1975).
This
study
was
judged
acceptable
without
metabolic
activation
but,
overall,
was
considered
inconclusive
(
HED
doc.
#
007765).

In
addition,
DDVP
is
a
direct
acting
mutagen
in
some
in
vitro
mammalian
test
systems.
For
instance,
in
the
forward
mutation
assay
at
the
TK
locus
(
L5178Y/
TK+/­)
of
cell
cultured
mouse
lymphoma
cells,
DDVP
(
technical,
97.5%
a.
i.,
Lot
No.
11381­
23­
5)
was
tested
in
up
to
20
doses
ranging
from
0.0089
to
1.0
µ
l/
mL,
both
in
the
presence
or
absence
of
metabolic
activation.
Concurrent
negative
controls
(
DMSO)
and
positive
controls
were
run
using
ethylmethanesulfonate
(
EMS)
for
nonactivated
and
7,12­
dimethylbenz[
a]
anthracene
(
DMBA)
for
activated
cultures.
The
test
article
was
completely
cytotoxic
(
0%
growth)
at
doses
 
1
µ
l/
mL
and,
therefore
doses
 
0.33
µ
l/
mL
were
used
to
ascertain
cloning
and
mutagenesis.
In
the
absence
of
metabolic
activation,
there
was
a
doserelated
(
0.024­
0.33
µ
l/
mL)
increase
in
mutant
frequencies
of
2.3­
13.3
times
that
of
DMSO
control.
Addition
of
metabolic
activation
seemed
to
diminish
the
mutation
frequency
where
at
the
two
highest
tested
doses
of
0.24
and
0.18
µ
l/
mL
the
mutant
frequency
was
3.7
and
2.7
times
DMSO,
respectively.
Similar
results
were
seen
when
the
test
was
repeated
in
a
second
series
of
experiments
with
and
without
metabolic
activation.
Positive
control
chemicals
elicited
appropriate
responses
where,
relative
to
solvent
control,
mutant
frequency
was
induced
by
6.8
to
16.3x
with
EMS
in
nonactivated
cultures
and
by
2.2
to
6.3x
with
DMBA
in
S­
9
activated
cultures
(
Microbiological
Associates,
Inc.,
Study
No.
T­
5211.702003,
dated
10/
14/
86,
Acc.
No.
265524).
This
study
was
considered
acceptable
(
TXR
#
005663).

Positive
results
were
also
described
in
another
TK
mouse
lymphoma
forward
mutation
assay
where
DDVP
(%
a.
i.
not
specified)
was
tested
at
seven
concentrations
ranging
from
6.25­
250
nl/
mL
in
the
absence
of
metabolic
activation
only.
No
cells
survived
at
the
two
highest
doses
of
200
and
250
nl/
mL
but
at
the
dose
100
nL/
mL
the
mutant
frequency
was
7.6x
the
solvent
control
(
EtOH)
while
the
positive
control
(
methylmethanesulfonate)
responded
appropriately
yielding
5.4x
the
mutation
frequency
of
EtOH.
A
repeat
test
gave
similar
qualitative
results.
(
Study
performed
by
Litton
Bionetics
under
contract
to
NTP/
NIEHS,
report
dated
8/
27/
85,
Acc.
No.
259463).
Despite
the
apparent
direct
acting
mutagenicity
results
by
DDVP,
this
study
was
considered
inconclusive
as
a
"
comprehensive
mutagenicity
test
in
this
system"
because
no
S­
9
metabolic
activation
was
done
(
TXR
#
004376).
Page
139
of
151
DDVP
seems
to
also
have
clastogenic
activity
by
inducing
chromosomal
aberrations
(
AB),
sister
chromatid
exchanges
(
SCE),
and
polyploidy
in
cultured
Chinese
hamster
ovary
(
CHO)
cells
(
Tezuka
et
al.,
1980).
To
3x105
pre­
cultured
CHO
cells,
DDVP
(
a.
i.
>
98%)
in
DMSO
(
final
concentration
of
solvent
in
culture
was
kept
to
1%)
was
added
at
a
final
DDVP
concentration
of
0,
1x10­
4,
2x10­
4,
5x10­
4,
and
1x10­
3
M.
After
adding
5­
bromomodeoxyuridine
to
a
final
concentration
of
2
µ
M,
each
culture
was
incubated
for
26.5
hr
in
the
dark.
All
doses
were
run
in
duplicate
using
established
procedures,
where
50
and
100
metaphases
were
generally
used
for
scoring
and
detecting
SCEs
and
ABs,
respectively,
at
each
concentration.
There
was
a
statistically
significant
(<
0.001)
dosedependent
increase
in
the
mean
number
of
SCE/
cell
with
a
maximum
increase
over
control
of
nearly
5­
fold
at
the
5x10­
4M
concentration
(
no
data
was
available
at
the
highest
dose
tested
and
no
explanation
given).
Chromosomal
aberrations
also
were
induced
(
p<
0.001)
at
the
5x10­
4M
DDVP
concentration
where,
of
100
scored
cells,
AB
were
found
in
34
cells
compared
to
9/
200
for
control
and
4/
100
for
each
of
the
two
lowest
DDVP
doses
(
no
data
and
no
explanation
were
available
for
the
highest
dose
tested).
There
were
no
cells
with
10
or
more
AB
per
cell.
Increased
polyploidy
was
also
observed
at
the
three
lowest
DDVP
doses
(
no
data
was
available
for
the
highest
dose)
where
the
per
cent
of
examined
cells
with
polyploidy
ranged
from
9.3
to
15.7
%,
compared
to
2.5%
in
control
cells.
According
to
the
"
Discussion"
in
this
article,
previous
studies
with
DDVP
in
cultured
human
lymphocytes
or
fibroblasts
did
not
show
inductions
of
SCE
or
AB,
and
this
apparent
divergence
with
the
results
of
this
study
was
attributed
to
possible
differences
in
sensitivity
among
the
different
test
systems
(
Tezuka
et
al.,
1980).

According
to
a
Memorandum
(
dated
August
10,
1988)
entitled,
"
Review
of
in
vivo
mutagenicity
studies
concerning
Dichlorvos"
that
was
presented
to
the
Cancer
Peer
Review
Committee
(
CPRC)
by
Kerry
Deerfield,
DDVP
is
also
clastogenic
(
causing
AB
and
SCE)
in
CHO
cells
with
or
without
metabolic
activation
(
NTP
draft
report,
1987,
TR
342,
NIH
pub.
No.
88­
2598).
[
The
review
by
K.
Dearfield
mistakenly
cites
that
the
test
system
in
the
above
study
by
Tezuka
et
al.,
1980
used
V79
cells
(
hamster
fibroblasts)
rather
than
CHO
cells.]
This
NTP
study
is
not
available
to
this
reviewer
to
clarify
and
provide
more
details.

As
shown
below,
however,
an
in
vivo
study
by
Microbiological
Associates,
Inc.
(
Study
dated
9/
26/
85)
failed
to
show
that
DDVP
has
clastogenic
activity
in
mice.

Mutagenicity
Studies
with
Negative
Results
In
a
micronucleus
test,
DDVP
(
98.5%
a.
i.,
in
corn
oil)
was
administered
(
i.
p.)
at
0
(
vehicle),
4,
13,
or
40
mg/
kg/
day
to
adult
CD­
1
mice
(
5/
sex/
dose/
scheduled
sacrifice)
on
two
consecutive
days
and
bone
marrow
polychromatic
erythrocytes
(
PCE)
were
examined
for
micronuclei
at
30,
48,
and
72
hr
after
the
last
dose.
A
group
(
5/
sex)
of
positive
control
mice
were
administered
(
i.
p.)
a
single
dose
(
0.15
mg/
kg)
of
the
mutagen
triethylene
melamine
(
TEM)
in
water
at
30
hr
prior
to
killing.
From
a
preliminary
DDVP
dose­
range
finding
study
(
8
doses
from
1
to
100
mg/
kg)
the
LD50
for
both
sexes
is
56
mg/
kg.
In
the
main
assay,
two
males
and
three
females
in
the
high
dose
group
and
one
male
in
the
mid
dose
group
died
prior
to
scheduled
killing.
(
Dead
animals
in
the
high
dose
group
were
replaced.)
Also
lethargy
and
tremors
were
seen
in
the
high
dose
group.
Therefore,
a
clinical
MTD
seems
to
have
been
achieved.
Page
140
of
151
In
none
of
the
18
DDVP
test
groups
were
micronuclei
significantly
increased
(
range
0­
1.2
per
1000
scored
PCE)
compared
to
negative
control
(
0­
1).
There
was
a
significant
response
in
the
TEM
positive
control
group
with
a
mean
of
15.6
(
males)
and
13.2
(
females)
micronuclei/
1000
PCE.
(
Microbiological
Associates,
Inc.,
Study
dated
8/
15/
85)
This
study
was
classified
as
acceptable/
current
guideline
(
HED
doc.
#
004376).

In
another
in
vivo
mutagenicity
study,
DDVP
(
98.5%
a.
i.,
in
corn
oil)
was
tested
for
sister
chromatid
exchange
(
SCE)
induction
in
B6C3F1
mice
(
5/
sex/
group)
which
were
implanted
(
s.
c.)
with
50
mg
bromodeoxyuridine
pellet
four
hours
prior
to
receiving
a
single
injection
(
i.
p.)
of
0
(
corn
oil),
3,
10,
or
30
mg
DDVP/
kg.
Dose­
selection
for
this
study
was
based
on
a
preliminary
study
in
which
mice
received
one
of
eight
doses
ranging
from
1­
100
mg
DDVP/
kg
where
the
combined
(
male/
female)
LD50
was
calculated
as
47
mg/
kg.
A
positive
control
group
(
5/
sex)
received
an
i.
p.
injection
of
cyclophosphamide
(
CP)
at
10
mg/
kg
in
water.
After
24
hours,
bone
marrow
from
both
femurs
was
removed
and
processed
to
determine
SCE
by
standardized
methods
where
fifty
second­
division
metaphase
cells
per
animal
were
scored
for
SCE.
No
animals
died
in
the
main
SCE
assay
and
no
clinical
signs
of
toxicity
were
observed
except
for
lethargy
in
the
high
dose
group.
The
mean
SCE/
cell/
animal
were
similar
among
all
animals
in
the
negative
control
and
the
DDVP­
treated
groups
(
males:
4.9­
5.9/
females:
5.6­
6.3);
also
the
mitotic
indices
(%
of
metaphase
cells
in
first,
second,
and
third
division)
in
all
DDVP
treated
groups
were
comparable
to
the
negative
control
group
indicating
that
there
was
no
cell
cycle
delay
even
at
the
highest
DDVP
dose.
As
expected,
CP
was
positive
with
a
mean
SCE/
cell/
animal
of
29.9
in
males
and
18.1
in
females.
(
Microbiological
Associates,
Inc.,
Study
dated
9/
26/
85)

This
study
was
classified
as
acceptable
and
HED
concluded
that
"
although
no
evidence
for
target
cell
toxicity
(
mitotic
delay)
was
reported
even
at
a
dose
causing
clinical
toxicity,
the
study
was
otherwise
conducted
adequately,
and
thus
the
negative
results
for
SCE
are
supportable."
(
HED
doc.
#
004376)

This
reviewer
partly
disagrees
since
the
highest
tested
dose
of
30
mg/
kg
was
below
the
MTD
as
judged
by
an
LD50
of
47
mg/
kg
(
preliminary
study)
and
a
lack
of
clinical
signs
of
toxicity
with
the
exception
of
lethargy.

Another
in
vivo
study
(
MRID
no.
42619901)
assessed
the
potential
for
genotoxic
effects
in
the
germ
cells
and
in
bone
marrow
in
male
ICR
mice
(
10/
group)
by
administering
daily
oral
(
gavage)
doses
of
0,
12.5,
25,
or
50
mg/
kg/
day
of
DDVP
(
a.
i.
98.1%,
dissolved
in
water
to
give
a
constant
dosing
volume
of
20
mL/
kg)
for
five
consecutive
days.
Cyclophosphamide
(
CP)
was
also
administered
(
10
mice/
group)
at
a
single
oral
dose
of
40
or
150
mg/
kg
(
in
water,
dosing
volume
20
mL/
kg).
All
animals
also
received
a
single
i.
p.
injection
(
1.6
mg/
kg)
of
the
spindle
inhibitor
colchicine
two
hours
before
killing.
Bone
marrow
cells
and
spermatogonia
were
prepared
according
to
established
procedures;
from
each
animal,
fifty
metaphase
cells
were
examined,
structural
aberrations
were
recorded,
and
the
mitotic
index
(
MI)
was
determined.
There
were
no
indication
of
a
clastogenic
effect
in
either
germinal
(
spermatogonia)
or
somatic
cells
(
bone
marrow)
harvested
24
hours
following
the
final
administration
of
the
test
material.
The
positive
control
group
responded
appropriately.
The
reviewer
of
this
study
concluded
that
the
maximally
tolerated
dose
was
achieved
based
on
a
preliminary
test
where
there
was
80
%
mortality
after
a
single
dose
of
70
mg
DDVP/
kg
Page
141
of
151
(
100%
mortality
after
a
single
dose
of
 
90
mg/
kg);
furthermore,
the
five
repeated
doses
of
DDVP
"
allowed
a
slightly
reduced
dosing
load
while
challenging
the
animals
without
excessive
mortality"
as
was
seen
at
 
70mg/
kg.

This
study
(
MRID
No.
42619901)
was
judged
acceptable
and,
therefore,
it
satisfied
the
requirement
for
in
vivo
cytogenetic
mutagenicity
data
(
HED
doc.
#
010446).

h.
Metabolism
CITATION:
Cheng,
T.
(
1989)
Metabolism
of
(
Carbon
14)­
DDVP
in
Rats:
Project
ID
HLA
6274­
105.
Unpublished
study
prepared
by
Hazleton
Laboratories
America,
Inc.
322
p.
MRID
41228701.

Cheng,
T.
(
1991)
Supplement
to:
Metabolism
of
carbon
14|­
DDVP
in
Rats
(
Preliminary
and
Definitive
Phases)
(...):
Lab
Project
Number:
HLA
6274­
105­
1.
Unpublished
study
prepared
by
Hazleton
Laboratories
America,
Inc.
89
p.
MRID
41839901.

EXECUTIVE
SUMMARY:
Groups
of
Sprague­
Dawley
rats
(
5/
sex/
group)
were
administered
a
single
dose
of
20
µ
Ci
[
14C]
DDVP
(
radiolabelled
at
the
vinyl
position
and
purified
to
100%)
either
intravenously
(
1
mg/
kg),
orally
(
1
or
20
mg/
kg;
low
and
high
doses,
respectively),
or
orally
(
1
mg/
kg)
after
15
daily
oral
doses
of
unlabeled
DDVP
(
1
mg/
kg)
and
a
control
group
(
2/
sex)
were
orally
dosed
with
water
(
vehicle).
Of
the
total
orally
administered
dose
(
low
or
high),
nearly
88­
94%
was
absorbed
through
the
gastrointestinal
tract
and,
within
24
hr,
nearly
43­
57%
of
the
original
dose
(
low
or
high)
was
eliminated
in
expired
air
and
excreta.
After
seven
days,
the
total
excreted/
air
expired
recovery
was
approximately
60­
77%;
and,
of
the
original
dose,
11­
17%
was
recovered
in
urine/
cage
washes,
4­
7%
in
feces,
and
41­
58%
as
expired
14CO2.
The
relative
amounts
of
radioactivity
retained
in
carcass,
liver,
and
other
tissues
combined
were
13­
26%,
3­
5%,
and
1­
2%,
respectively.
During
the
seven
days
post­
dosing
period
(
low
or
high
single
dose),
males
expired
slightly
less
14CO2
than
females
(
41­
45%
vs.
52­
54%,
respectively).
The
excretion
patterns
were
similar
after
i.
v.
or
oral
administration
and
little,
if
any,
other
differences
relating
to
sex
or
dose
were
found
in
the
excretion
or
distribution
of
[
14C]
DDVP.
Of
the
five
radiolabelled
compounds
that
were
detected
in
urine,
two
were
identified
by
mass
spectrometry
as
hippuric
acid
(
HA)
and
urea.
Relative
to
total
urinary
radioactivity,
the
concentration
of
HA
ranged
from
6.8­
10.5
%
(
low
dose
group)
to
4.2­
5.6
%
(
high
dose
group),
while
the
amount
of
urea
was
19.6­
33.1%
(
low
dose
group)
and
41.1­
51.1%
(
high
dose
group).
Urea
and
HA
also
seemed
to
be
present
in
feces,
albeit
at
lower
concentrations
than
were
found
in
urine.
Three
other
urinary
compounds
were
not
identified
but
were
assumed
to
be
dehalogenated
metabolites.
Other
metabolites,
representing
nearly
8
to
19%
of
total
urinary
radioactivity,
were
considered
to
be
glucuronide
conjugates
(
not
identified).

The
overall
metabolic
profile
suggests
the
involvement
of
the
one­
carbon
pool
biosynthetic
pathway
as
evidenced
by
the
presence
of
a
relatively
large
amount
of
radioactivity
in
the
form
of
expired
14CO2
and
the
presence
of
dehalogenated
metabolites
as
well
as
urea
and
hippuric
acid.
These
studies
(
MRID
#
41228701
and
41839901)
were
considered
acceptable
and
should
satisfy
the
guideline
requirement
for
a
metabolism
study
(
HED
doc.
#
008132
and
009444).
Page
142
of
151
It
should
be
noted
that
the
above
metabolism
summary
was
based
on
the
specified
subject
MRID
and
HED
documents
and,
as
a
result,
subtle
differences
or
disagreements
(
for
instance,
relative
amounts
of
metabolites)
are
inevitable
between
this
summary
and
other
metabolism
summaries
(
e.
g.,
the
document
dated
August
28,
1996
and
entitled,
"
fifth
carcinogenicity
peer
review
of
dichlorvos"
prepared
by
Joycelyn
Stewart).

It
should
also
be
pointed
out
that,
according
to
the
IRIS
summary
on
dichlorvos
dated
09/
01/
96,
there
are
several
additional
published
studies
on
the
availability,
distribution,
and
metabolism
following
administration
of
DDVP
by
different
routes
to
different
species.

I.
Human
Studies
CITATION:
Gledhill,
A.
(
1997)
Dichlorvos:
A
Study
to
Investigate
the
Effect
of
a
Single
Oral
Dose
on
Erythrocyte
Cholinesterase
Inhibition
in
Healthy
Male
Volunteers:
Lab
Project
Number:
CTL/
P/
5393:
XH6064.
Unpublished
study
prepared
by
Zeneca
Central
Toxicology
Lab.
44
p.
MRID
44248802.

Gledhill,
A.
(
1997)
Dichlorvos:
A
Single
Blind,
Placebo
Controlled,
Randomised
Study
to
Investigate
the
Effects
of
Multiple
Oral
Dosing
on
Erythrocyte
Cholinesterase
Inhibition
in
Healthy
Male
Volunteers:
Lab
Project
Number:
CTL/
P/
5392:
XH6063.
Unpublished
study
prepared
by
Zeneca
Central
Toxicology
Lab.
52
p.
MRID
44248801.

Gledhill,
A.
(
1997)
Dichlorvos:
A
Study
to
Investigate
Erythrocyte
Cholinestrase
Inhibition
Following
Oral
Administration
to
Healthy
Male
Volunteers:
Lab
Project
Number:
XH5170:
Y09341:
C05743.
Unpublished
study
prepared
by
Zeneca
Central
Toxicology
Lab.
104
p.
MRID
44416201.

EXECUTIVE
SUMMARY:
Dichlorvos
(
lot
no.
608002S074,
a.
i.
98%,
dissolved
in
corn
oil
and
packed
in
capsule)
was
administered
in
a
single
oral
dose
of
70
mg
(
equivalent
to
1
mg/
kg)
to
six
fasted
young
healthy
male
volunteers.
RBC
cholinesterase
(
ChE)
activity
was
measured
prior
to
dosing
on
days
­
22,
­
20,
­
18,
­
15,
­
13,
­
11,
­
8,
­
6,
­
4,
and
0
(
immediately
prior
to
dosing),
and
after
DDVP
administration
on
days
1,
3,
5/
6,
7,
and
14.
All
subjects
were
medically
supervised
for
clinical
signs
and
body
temperature
changes
for
twenty
four
hours
after
dosing.
Under
the
study
conditions,
no
adverse
clinical
signs
and
no
body
temperature
variations
were
reported.
Mean
RBC
ChE
activity
was
statistically
significantly
inhibited
by
12%
or
less
on
days
5/
6,
day
7,
and
day
14.
The
reduction
in
RBC
ChE
was
not
considered
to
be
biologically
meaningful.
This
study
is
considered
non­
guideline
(
MRID
#
44248802).

In
a
single
blind
oral
study,
each
of
six
fasted
male
volunteers
was
administered
a
daily
dose
of
7
mg
DDVP
(
equivalent
to
about
0.1
mg/
kg/
day)
in
corn
oil
via
a
capsule
over
21
days.
Three
control
subjects
received
corn
oil
as
a
placebo.
The
activity
of
RBC
ChE
was
measured
for
each
participant
prior
to
dosing,
to
establish
baseline
levels,
and
also
after
dosing
on
days
2,
4,
7,
9,
11,
14,
16,
18,
25,
and
28.
There
were
no
reported
toxicity
attributable
to
DDVP
administration.
Compared
to
Page
143
of
151
pre­
dosing
mean
value,
the
mean
RBC
ChE
activity
was
statistically
significantly
reduced
by
8,
10,
14,
14,
and
16
percent
on
days
7,
11,
14,
16,
and
18,
respectively.
Under
the
study
conditions,
the
LOAEL
for
RBC
ChE
inhibition
was
established
at
0.1
mg/
kg/
day
(
MRID
No.
44248801).
As
discussed
below,
this
study
was
used
for
intermediate­
term
dermal
exposure
risk
assessment.

In
another
human
study
(
MRID
44416201),
DDVP
(
lot
no.
402010A,
a.
i.,
98%,
dissolved
in
corn
oil
and
packed
in
a
capsule)
was
administered
to
each
of
six
fasted
healthy
male
Caucasian
males
over
two
experimental
phases
where
each
phase
was
followed
by
repeated
measurements
of
RBC
ChE.
In
the
first
phase,
volunteers
ingested
a
capsule
of
35
mg
DDVP
on
day
1,
and
on
day
8
or
9
they
received
a
corn
oil
capsule
and
finally
they
received
another
35
mg
DDVP
capsule,
eight
or
nine
days
after
the
corn
oil.
Measurements
of
RBC
ChE
were
performed
pretest
(
days
­
7,
­
5,
and
­
3)
and
after
administration
of
each
DDVP
capsule
(
24,
72,
120,
and
168
hr
post
each
dose)
or
corn
oil
(
at
24,
72,
and
120
hr).
Adverse
physical
signs
and
symptoms
including
body
temperature
were
recorded
for
each
volunteer.
After
24
hr
and
120
hr
of
the
first
DDVP
dosing,
group
mean
RBC
ChE
activities
were
significantly
depressed
to
88%
(
not
93%
as
reported
by
original
reviewer
in
DER
#
22)
and
90
%,
respectively,
of
predosing
levels.
(
There
seems
to
be
an
error
in
computing
the
day
1
group
mean
ChE
level
after
the
first
DDVP
dosing
which
should
be
15098
I.
U.,
or
88%,
instead
of
15908
I.
U.,
or
93%,
as
shown
in
Table
2
of
DER
#
22.)
However,
following
the
second
dose
of
DDVP,
there
were
no
statistically
significant
changes
in
group
mean
RBC
ChE
activity
at
any
time
(
94
­
98%
of
predose
activity).
Also,
no
changes
in
ChE
values
were
seen
after
dosing
with
corn
oil
(
96
­
105%
of
predosing).
Individual
post­
dose
ChE
activity
ranged
from
80%
to
103%
(
not
85
to
100%
as
per
DER
#
22)
of
predose
values
at
all
reporting
periods.
There
were
no
changes
in
body
temperature
and
no
symptoms
were
attributed
to
DDVP.

In
the
second
phase
of
this
study,
the
same
volunteers
were
administered
repeated
daily
doses
of
21
mg
DDVP
for
12
or
14
days
and
RBC
ChE
activity
was
monitored
every
two
or
three
days
up
to
day
29,
and
also
on
days
33,
40
and
55
(
Table
3,
DER
#
22)
or
on
days
33,
40,
47,
and
54,
instead
of
days
33,
40
and
55
(
as
specified
under
Section
2
entitled
"
Study
Design"
in
DER
#
22).
Plasma
was
also
prepared
from
all
blood
samples
and
immediately
frozen
and
stored
at
­
20
°
C;
however,
plasma
ChE
was
not
measured.
Compared
to
the
group
mean
pretest
value,
group
mean
RBC
ChE
activity
was
significantly
decreased
(<
0.01)
from
day
5
through
day
33,
reaching
a
minimum
of
69%
on
day
22
after
which
it
seemed
to
gradually
recover
until
the
last
measurement
on
day
54
(
or
55)
when
it
was
91%
of
pretest
activity.
Four
of
the
six
subjects
reported
various
symptoms;
one
felt
tired
(
days
5­
9)
with
headache
and
nausea
(
day
6),
another
felt
anxious
one
hour
after
the
first
dose,
a
volunteer
had
an
abdominal
colic
(
day
12),
and
one
subject
developed
an
upper
respiratory
tract
infection
(
days
7
thru
12).
Despite
the
fact
that
these
symptoms
(
with
the
possible
exception
of
upper
respiratory
tract
infection)
are
typical
indicators
of
cholinesterase
poisoning,
the
investigators
ruled
out
DDVP
as
a
possible
cause.

According
to
DER
#
22,
the
HED
study
reviewer
concluded
that,
based
on
no
decrease
in
RBC
ChE
in
phase
1,
NOAEL
is
35
mg/
person
(
or
0.5
mg/
kg
for
an
average
70
kg
person).
This
reviewer,
however,
does
not
think
that
NOAEL
was
achieved
since,
compared
to
pretest
value,
the
group
mean
RBC
ChE
was
statistically
significantly
depressed
to
88%
(
day
1)
and
90%
(
day
5)
and
also
because,
at
day
1,
one
individual
(#
IV)
had
this
enzyme
activity
drop
to
nearly
80%
of
pretest
level
(
Table
1
in
DER
#
22);
furthermore,
the
reported
physical
symptoms
in
four
subjects
(
three
if
the
Page
144
of
151
upper
respiratory
tract
infection
is
deemed
unrelated)
appear
to
be
characteristic
of
ChE
poisoning.
In
phase
2,
based
on
the
steady
decline
in
RBC
ChE
activity,
the
original
HED
reviewer
concluded
that
"
NOAEL
has
not
been
established
for
this
portion
of
the
study."
This
study
is
considered
non­
guideline
(
MRID
No.
44416201).

Other
human
studies
(
journal
articles)
were
also
reviewed
and
were
considered
supplementary
due
to
employing
too
few
subjects
and/
or
lacking
individual
data
(
Stewart,
1993;
HED
document
No.
010157
and
Dannon,
1998)
Page
145
of
151
3.0
Residue
Chemistry
Science
Assessments
for
Reregistration
of
Dichlorvos.

GLN:
Data
Requirements
Current
Tolerances,
ppm
[
40
CFR]
Must
Additional
Data
Be
Submitted?
References
1
860.1200:
Directions
for
Use
N/
A
=
Not
Applicable
Yes
2
860.1300:
Plant
Metabolism
N/
A
No
00013545,
00074844,

860.1300:
Animal
Metabolism
N/
A
No
00013546,
00066696,
00117261,
00117262,
00126462,
00126463,
42721601
3
,
42951701
4
860.1340:
Residue
Analytical
Methods
­
Plant
commodities
N/
A
No
00042702,
00042704,
00042706,
00047472,
00049086,
00049971,
00049975,
00051556,
00074706,
00074777,
00107572,
00115993,
00117747,
00118115,
00139845
­
Animal
commodities
N/
A
No
00042702,
00042704,
00049086,
00049087,
00049975,
00060469,
00060470,
00060472,
00074706,
00115939,
00115993,
00117257,
00117747,
00118113,
00118592,
00118639,
00140392
860.1360:
Multiresidue
Methods
N/
A
No
42611001
5
860.1380:
Storage
Stability
Data
N/
A
Yes
6
00074776,
00076809,
00140392,
43377701
7
860.1500:
Crop
Field
Trials
Root
and
Tuber
Vegetables
Group
­
Radishes
0.5
[
180.235(
a)]
No
8
00118572,
00119536
Page
146
of
151
GLN:
Data
Requirements
Current
Tolerances,
ppm
[
40
CFR]
Must
Additional
Data
Be
Submitted?
References
1
Leafy
Vegetables
(
except
Brassica
Vegetables)
Group
­
Lettuce
1
8
[
180.235(
a)]
No
8
00033139,
00082271,
00118572,
00119536
Fruiting
Vegetables
(
except
Cucurbits)
Group
­
Tomatoes
0.05
9
[
180.235(
a)]
No
8
00033144,
00107572,
00115993,
00117686,
00118169,
00118572
Cucurbit
Vegetables
Group
­
Cucumbers
0.5
9
[
180.235(
a)]
No
8
00082271,
00107572,
00118572
Miscellaneous
Commodities
­
Mushrooms
0.5
9
[
180.235(
a)
No
00074658,
00117686,
00117690
­
Tobacco
None
established
No
10
860.1520:
Processed
Food/
Feed
­
Corn,
field
0.5
(
processed
food)
10
[
185.1900]
No
42993501
13
­
Cottonseed
0.5
(
processed
food)
11
[
185.1900]
No
42993501
13
­
Rice
0.5
(
processed
food)
11
[
185.1900]
No
42993501
13
­
Peanuts
0.5
(
processed
food)
11
[
185.1900]
No
42952601
7
­
Soybeans
0.5
(
processed
food)
11
[
185.1900]
No
42993501
13
Page
147
of
151
GLN:
Data
Requirements
Current
Tolerances,
ppm
[
40
CFR]
Must
Additional
Data
Be
Submitted?
References
1
­
Wheat
0.5
(
processed
food)
11
[
185.1900]
No
42993501
13
860.1480:
Meat,
Milk,
Poultry,
Eggs
­
Milk
and
the
Fat,
Meat,
and
Meat
Byproducts
of
Cattle,
Goats,
Hogs,
Horses,
and
Sheep
0.02
(
milk
and
the
fat,
meat,
and
meat
byproducts
of
cattle,
goats,
horses,
and
sheep)
[
180.235(
a)]
0.1
(
edible
tissue
of
swine)
[
180.235(
b)]
Yes
12
00115945,
00116436,
43037401
13
­
Eggs
and
the
Fat,
Meat,
and
Meat
Byproducts
of
Poultry
0.05
[
180.235(
a)]
No
00118639,
00119537,
00139843,
00139844,
43047901
13
860.1400:
Water,
Fish,
and
Irrigated
Crops
None
established
No
860.1460:
Food
Handling
­
Food
Service
Establishments
None
established
No
­
Grain
Processing
and
Manufacturing
Establishments
0.5
(
RAC)
14
[
180.235(
a)]
42768702
13
,
42775901
13
,
42878801
13
,
42910801
13
,
42910901
13
­
Bulk
Stored
Raw
and
Processed
Commodities
15
0.5
(
RAC)
14
[
180.235(
a)]
No
00117747,
42916601
7
­
Bulk
stored
peanuts
15
0.5
[
180.235(
a)]
No
43003101
7
­
Packaged
and
Bagged
Raw
and
Processed
Commodities
0.5
(
RAC,
 
6%
fat)
11
2
(
RAC,
>
6%
fat)
11
[
180.235(
a)]
0.5
(
processed
food)
11
[
185.1900]
No
00056593,
00056595,
00056596,
42853701
7
Page
148
of
151
GLN:
Data
Requirements
Current
Tolerances,
ppm
[
40
CFR]
Must
Additional
Data
Be
Submitted?
References
1
­
Crack
and
Crevice
Treatments
None
established
No
16
860.1000:
Reduction
of
Residue
­
Dried
Beans
N/
A
No
42910701
13
­
Cocoa
Beans
N/
A
No
42910701
13
­
Coffee
Beans
N/
A
No
42910701
13
­
Tomato
N/
A
No
42910701
13
­
Meat,
Eggs,
Pasteurized
Milk
N/
A
No
42910701
13
­
Degradation
­
Packaged
and
Bagged
Raw
and
Processed
Commodities
N/
A
No
17
42858201
13
­
Degradation
­
Bulk
Stored
Raw
and
Processed
Commodities
N/
A
No
17
42903801
7
860.1850:
Confined
Rotational
Crops
N/
A
No
8
860.1900:
Field
Rotational
Crops
None
No
8
Page
149
of
151
1
References
without
endnotes
were
reviewed
in
the
Residue
Chemistry
Chapter
of
the
Dichlorvos
Reregistration
Standard
dated
2/
26/
86.
All
other
references
were
reviewed
as
noted.

2.
Label
amendments
are
required
to
incorporate
the
parameters
of
use
patterns
reflected
in
the
submitted
data
and
to
reflect
the
use
patterns
that
the
registrant
wishes
to
support
which
are
supported
by
residue
data.
Product
labels
with
uses
in
mushroom
houses
must
be
amended
to
reflect
a
1­
day
PHI.
All
uses
in
greenhouses
(
food
use
only)
and
tobacco
warehouses
must
be
deleted
from
product
labels.
Product
labels
which
allow
uses
in
food­
handling
establishments
must
be
amended
to
specify
that
applications
may
only
be
made
in:
in
warehouses,
silos,
bulk
bins,
and
food/
feed
processing,
food/
feed
manufacturing,
handling
and
storage
plants
containing
nonperishable
packaged
or
bagged
raw
or
processed
food/
feed
commodities
or
bulk
raw
or
processed
food
commodities;
or
in
non­
food
areas
of
food­
handling
establishments
[
including
garbage
rooms,
lavatories,
floor
drains
(
sewers),
entries
and
vestibules,
offices,
locker
rooms,
machine
rooms,
boiler
rooms,
garages,
mop
closets,
and
storage
(
after
canning
or
bottling)].
Use
in
food
handling
establishments
­
food
service
areas
must
be
canceled.
There
are
no
tolerances
or
data
supporting
this
use.

3
CB
No.
11768,
DP
Barcode
D190450,
7/
21/
93,
D.
McNeilly.

4.
CB
No.
12766,
DP
Barcode
D196572,
12/
17/
93,
D.
McNeilly.

5.
CB
No.
11244,
DP
Barcode
D187061,
9/
29/
93,
D.
McNeilly.

6.
Information
pertaining
to
the
storage
intervals
and
conditions
of
samples
of
the
following
commodities,
from
studies
that
were
reviewed
in
the
Residue
Chemistry
Chapter
of
the
Registration
Standard
(
1987),
must
be
submitted:
packaged
and
bagged
raw
agricultural
commodities
and
processed
food;
bulk
stored
raw
agricultural
commodities;
milk;
eggs;
and
meat,
fat,
and
meat
byproducts
of
dairy
cows
and
poultry.
Alternatively,
the
registrant
may
demonstrate
that
there
are
sufficient
residue
data
supported
by
storage
stability
data
to
support
all
registered
uses
of
dichlorvos.

7.
CB
Nos.
12658,
13230,
13296,
and
13297;
DP
Barcodes
D195720
,
D199212,
D199977,
and
D199979;
6/
2/
94;
S.
Hummel.

8.
The
registrant
is
not
supporting
any
agricultural
uses
of
dichlorvos.
Another
registrant
has
indicated
a
willingness
to
support
dichlorvos
use
on
tomatoes.
If
this
use
is
to
be
supported,
residue
data
are
required.
We
note
that
the
tomato
use
is
no
longer
on
any
dichlorvos
labels.

9.
Residues
are
expressed
as
naled.

10.
The
registrant
is
not
supporting
use
of
dichlorvos
in
tobacco
warehouses.

11.
Resulting
from
application
to
packaged
or
bagged
nonperishable
commodities.

12.
A
dermal
magnitude
of
the
residue
study
must
be
submitted
for
swine.
Swine
dermal
use
remains
on
dichlorvos
labels.

13.
CB
Nos.
13006,
13294,
13295,
13296,
and
13427;
DP
Barcodes
D197522
,
D199975,
D199976,
D199979,
and
D200905;
7/
18/
94;
S.
Hummel.
Non­
detectable
residues
were
reported
from
direct
dermal
uses
and
from
secondary
residues
in
livestock
feeds.

14.
Resulting
from
application
to
bulk
stored
nonperishable
commodities,
regardless
of
fat
content.

15.
See
also
"
860.1520:
Processed
Food/
Feed."
Page
150
of
151
16.
Data
had
been
required
reflecting
crack
and
crevice
treatment
of
food
handling
establishments;
however,
because
this
use
is
more
restrictive
than
the
registered
use
on
bulk
stored
and
packaged
and
bagged
commodities,
these
data
are
no
longer
required.

17.
Although
no
additional
data
are
required
concerning
this
guideline
topic
for
the
purposes
of
reregistration,
the
Agency's
risk
assessment
could
be
better
refined
if
the
registrant
provides
information
concerning
the
typical
length
of
time
commodities
remain
in
storage
following
treatment.
This
information
would
include
typical
total
storage
times,
frequency
of
applications,
and
rates
of
application
(
g/
1000
cu.
ft.).

4.0
Tolerance
Reassessment
Table
C.
Tolerance
Reassessment
Summary
for
Dichlorvos.

Commodity
Current
Tolerance,
ppm
Tolerance
Reassessment,
ppm
Comment/
[
Correct
Commodity
Definition]

Tolerances
Listed
Under
40
CFR
§
180.235(
a)(
1)*

Cattle,
fat
0.02(
N)
0.05
Harmonize
with
CODEX.

Cattle,
meat
0.02(
N)
0.05
Harmonize
with
CODEX.

Cattle,
mbyp
0.02(
N)
0.05
Harmonize
with
CODEX.

Cucumbers
0.5
1
Revoke
The
registrant
is
not
supporting
use
of
dichlorvos
on
this
commodity.
Tolerance
has
been
revoked.

Eggs
0.05(
N)
0.05
Goats,
fat
0.02(
N)
0.05
Harmonize
with
CODEX.

Goats,
meat
0.02(
N)
0.05
Harmonize
with
CODEX.

Goats,
mbyp
0.02(
N)
0.05
Harmonize
with
CODEX.

Horses,
fat
0.02(
N)
0.05
Harmonize
with
CODEX.

Horses,
meat
0.02(
N)
0.05
Harmonize
with
CODEX.

Horses,
mbyp
0.02(
N)
0.05
Harmonize
with
CODEX.

Lettuce
1
1
Revoke
The
registrant
is
not
supporting
use
of
dichlorvos
on
this
commodity.
Tolerance
has
been
revoked.

Milk
0.02(
N)
0.05
Harmonize
with
CODEX.

Mushrooms
0.5
1
0.5
The
tolerance
should
be
revised
to
be
expressed
in
terms
of
dichlorvos.

Poultry,
fat
0.05(
N)
0.05
Poultry,
meat
0.05(
N)
0.05
Poultry,
mbyp
0.05(
N)
0.05
Radishes
0.5
Revoke
The
registrant
is
not
supporting
use
of
dichlorvos
on
this
commodity.
Page
151
of
151
Commodity
Current
Tolerance,
ppm
Tolerance
Reassessment,
ppm
Comment/
[
Correct
Commodity
Definition]

Raw
agricultural
commodities,
nonperishable,
bulk
stored
regardless
of
fat
content
(
post­
H)
0.5
4.0
[
Raw
agricultural
commodities,
nonperishable,
bulk
stored]

Raw
agricultural
commodities,
nonperishable,
packaged
or
bagged,
containing
6
percent
fat
or
less
(
post­
H)
0.5
Raw
agricultural
commodities,
nonperishable,
packaged
or
bagged,
containing
more
than
6
percent
fat
(
post­
H)
2.0
4.0
[
Raw
agricultural
commodities,
nonperishable,
packaged
and
bagged]

Sheep,
fat
0.02(
N)
0.05
Harmonize
with
CODEX.

Sheep,
meat
0.02(
N)
0.05
Harmonize
with
CODEX.

Sheep,
mbyp
0.02(
N)
0.05
Harmonize
with
CODEX.

Tomatoes
(
pre­
and
post­
H)
0.05
1
Revoke
The
registrant
is
not
supporting
use
of
dichlorvos
on
this
commodity.

Tolerances
Listed
Under
40
CFR
§
180.235(
a)(
2)

Edible
swine
tissue
2
0.1
Revoke
Residue
data
have
been
required
and
not
submitted.

Tolerances
Listed
Under
40
CFR
§
180.235(
a)(
3)

Packaged
or
bagged
nonperishable
processed
food
0.5
4.0
The
tolerance
should
be
moved
to
§
180.235(
a)(
1).
[
Processed
food,
nonperishable,
packaged
or
bagged]

Tolerances
to
be
Proposed
Under
40
CFR
§
180.235(
a)

Soybean,
hulls
­­
15.0
Aspirated
grain
fractions
­­
20.0
*
Concurrently
with
the
revocation
of
the
tolerance
for
edible
swine
tissue
in
§
180.235(
a)(
2)
and
the
moving
of
the
tolerance
for
packaged
or
bagged
nonperishable
processed
food
in
§
180.235(
a)(
3),
§
180.235(
a)(
1)
should
be
redesignated
§
180.235(
a).
1
Residues
expressed
as
naled.
Another
registrant
has
expressed
interest
in
supporting
the
tolerance
on
tomato.
However,
data
have
been
required
and
not
submitted.
2
Resulting
both
from
its
use
as
an
anthelmintic
in
swine
feed
and
as
an
insecticide
applied
directly
to
swine;
prescribed
by
21
CFR
558.205
as
a
feed
additive
in
swine,
with
a
tolerance
of
0.1
ppm
for
residues
of
dichlorvos
in
edible
swine
tissue
listed
in
21
CFR
556.180.