Document ID: EPA-HQ-OPP-2004-0048-0008
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2004-06-18T04:00Z

UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
April
30,
2004
MEMORANDUM:

SUBJECT:
Residential
Exposure
Assessment
for
the
Tolerance
Reassessment
Eligibility
Decision
(
TRED)
Document
For
Amitraz
FROM:
Robert
Travaglini,
Chemist
Reregistration
Branch
3
Health
Effects
Division
(
7509C)

THRU:
Seyed
Tadayon,
Chemist
Reregistration
Branch
3
Health
Effects
Division
(
7509C)

TO:
Jose
Morales,
Chemist
Reregistration
Branch
3
Health
Effects
Division
(
7509C)

DP
Barcode:
D300299
PC
Codes:
106201
EPA
Reg
Nos:
2382­
104;
2382­
170
264­
614;
264­
625,
264­
636,
54382­
3
LUIS
Report:
03/
02
This
document
describes
the
residential
exposure
and
risk
assessment
for
the
EPA
Registered
insecticide
amitraz.
TABLE
OF
CONTENTS
1.0
EXECUTIVE
SUMMARY
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3
1.1
Background
and
Purpose
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3
1.2
Use
Patterns
and
Formulations
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3
1.3
Registered
Use
Sites
and
Frequency
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3
1.4
Hazard
Identification
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4
1.5
Residential
Exposure
&
Risk
Estimates
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4
2.0
INCIDENT
REPORTS
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7
3.0
RESIDENTIAL
EXPOSURE
AND
RISK
ASSESSMENT
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8
3.1
Residential
Exposures
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8
3.2
Residential
Exposure
&
Risk
Estimates:
Post­
Application
(
non­
cancer)
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9
3.3
Residential
Carcinogenic
Risk
Estimates:
Post­
Application
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11
References
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13
1.0
EXECUTIVE
SUMMARY
3
1.1
Background
and
Purpose
EPA
published
a
Registration
Eligibility
Document
(
RED)
for
amitraz
in
March,
1995.
In
the
RED,
EPA
assessed
occupational
applicator
exposure
to
amitraz
for
handlers
and
applicators
as
well
as
post­
application
occupational
exposure
resulting
from
agricultural
uses
registered
for
amitraz
at
that
time
including
cotton
and
pears.
Residential
uses
were
not
assessed
for
the
RED.

This
document
addresses
the
exposures
and
risks
associated
with
the
residential
uses
of
amitraz
only.
A
regulatory
review
of
residential
exposure
to
amitraz
[
N­
methylbis(
2,4­
xylyliminomethyl)
amine]
was
conducted
for
this
TRED
because
there
is
potential
exposure
to
non­
occupational
(
residential)
handlers
(
applicators)
during
handling
and
application
of
pet
collars
which
have
been
impregnated
with
the
active
ingredient
amitraz
to
dogs
for
the
prevention
of
canine
ticks
and
fleas.
There
is
also
potential
residential
post­
application
exposure
to
amitraz
for
the
duration
of
the
use
of
the
collar
on
the
dog.
Product
labeling
specifies
only
the
use
of
these
collars
on
dogs.

An
occupational
and/
or
residential
exposure
assessment
is
required
for
an
active
ingredient
if
(
1)
certain
toxicological
criteria
are
triggered
and
(
2)
there
is
potential
exposure
to
handlers
(
mixers,
loaders,
applicators)
during
use
or
to
persons
entering
treated
sites
after
application
is
complete.
Amitraz
toxicological
endpoints
were
selected
for
short­
and
intermediate­
term
exposures,
no
chronic
exposure
scenarios
are
thought
to
exist
for
amitraz.
In
addition,
amitraz
is
classified
as
a
Group
C
possible
human
carcinogen
and
it
has
a
Q
1*
of
2.83
x
10­
2.
Based
on
the
potential
for
exposure,
risk
assessments
are
required
for
residential
handlers
and
in
particular
for
residential
postapplication
scenarios.

1.2
Summary
of
Use
Patterns
and
Formulations
and
Target
Pests
As
of
the
date
of
this
document,
pesticide
products
containing
amitraz
are
intended
for
both
occupational
(
i.
e.,
cattle
dipping)
and
residential
uses
(
i.
e.,
dog
collars).
There
are
two
Federally
registered
dog
collar
products
impregnated
with
amitraz,
manufactured
in
France
for
Virbac
of
Fort
Worth,
Texas;
EPA
Reg.
Nos.
2382­
104
and
2382­
170.
Each
of
these
collars
contain
9.0%
amitraz
as
the
active
ingredient.
EPA
Reg.
No.
2382­
170
also
contains
0.5%
Pyripoxyfen
as
an
active
ingredient
and
each
product
label
contains
the
language
"
For
Veterinary
Use
Only".
According
to
product
labeling,
the
collars
kill
ticks,
fleas
and
flea
eggs
on
a
dog
for
three
months.
For
the
purposes
of
this
assessment,
HED
used
EPA
Reg.
No.
2382­
170*
to
estimate
potential
residential
exposure
to
the
insecticide
amitraz
via
it's
use
in
impregnated
pet
collars
on
domestic
dogs
for
the
prevention
of
fleas
and
ticks.

Amitraz
is
registered
insecticide;
for
residential
purposes
the
targeted
pests
are
ticks
and
fleas
on
dogs.

1.3
Registered
Use
Sites,
and
Frequency
4
Amitraz
is
registered
as
an
insecticide/
miticide
for
the
control
of
ticks,
mange
mites,
lice
on
domestic
livestock
such
as
dairy
and
beef
cattle
and
swine.
For
the
purposes
of
this
document,
HED
is
concerned
with
use
of
amitraz
on
dog
collars
for
the
control
of
fleas
and
ticks
on
the
dog.
According
to
the
labeling
associated
with
this
product,
the
collars
prevent
ticks
for
3
months,
therefore,
the
collars
can
be
applied
4
times
per
year.

1.4
Hazard
Identification
The
March
17th,
2004
report
of
the
Hazard
Identification
Assessment
Review
Committee
(
HIARC)
for
amitraz
identified
toxicological
endpoints
of
concern
for
amitraz.
All
calculations
completed
in
this
document
are
based
on
the
most
current
toxicity
information
available
for
amitraz.
Endpoints
used
to
complete
this
assessment
are
summarized
in
Table
2.
For
short
and
intermediate
term
dermal
and
inhalation
exposure,
a
NOAEL
of
0.25
mg/
kg/
day
with
a
LOAEL
of
1.0
mg/
kg/
day,
from
a
chronic
oral
study
based
on
CNS
depression
during
the
first
two
days
of
dosing
was
selected.
A
dermal
absorption
factor
of
8.0%
is
applied
for
dermal
exposure
for
route
to
route
extrapolation.

The
HIARC
determined
that
a
Margin
Of
Exposure
(
MOE)
of
1000,
based
on
an
uncertainty
factor
of
100X
for
traditional
inter
and
intra
species
variation
and
an
additional
10X
for
lack
of
acceptable
developmental
and
reproductive
data
is
adequate
for
residential
exposures.

On
October
31,
1990,
the
Cancer
Peer
Review
Committee
classified
Amitraz
as
a
Group
C
­
possible
human
carcinogen,
and
recommended
that,
for
the
purpose
of
risk
characterization,
a
low
dose
extrapolation
model
be
applied
to
the
experimental
animal
tumor
data
for
quantification
of
human
risk
(
Q
1
*).
A
Q1*
based
upon
female
rat
liver
(
carcinoma
and/
or
adenoma)
tumor
rates
was
generated
using
mg/
kg
b.
w.^
2/
3'
s/
day
cross
species
scaling
factor.
The
revised
unit
risk,
Q
1
*

(
mg/
kg/
day)­
1,
of
Amitraz
based
upon
female
mouse
liver
combined
adenoma
and
carcinoma
tumor
rates
is
2.83
x
10­
2
in
human
equivalents
(
converted
from
animals
to
humans
by
use
of
the
3/
4'
s
scaling
factor
­
Tox_
Risk
program,
Version
5.31,
K.
Crump,
2000).
The
dose
levels
used
from
the
107­
week
dietary
study
were
0,
25,
100,
and
400
ppm
of
Amitraz.

1.5
Residential
Exposure
&
Risk
Estimates
Although
HED
considers
the
residential
handler
scenario
as
having
potential
exposure
risk,
the
most
significant
exposure
of
concern
is
for
post­
application
scenarios
as
these
exposures
are
of
longer
duration
and
potentially
affect
more
sensitive
residents
including
infants
and
children.
Therefore
this
document
primarily
focuses
on
residential
post­
application
exposures
only,
and
does
not
address
residential
handlers.

All
post­
application
scenarios
resulted
in
MOEs
which
exceed
HED's
level
of
concern.
Post­
application
dermal
exposure
estimates
for
toddlers
indicate
MOEs
of
22.
Incidental
oral
post­
application
exposure
to
toddlers
from
amitraz
(
via
hand
to
mouth),
from
such
activities
hugging
the
dog
has
an
MOE
of
65.
For
adults,
dermal
post­
application
exposure
estimates
for
amitraz
via
such
an
activity
of
the
hugging
the
dog
indicate
MOEs
of
32.
5
Post­
application
cancer
risk
estimates
for
adults
range
from
2.8
­
5
to
5.6
­
5,
and
exceed
HED's
level
of
concern
1.4.1
Acute
Toxicity
Categories
Table
1.
represents
the
acute
toxicity
categories
outlined
in
the
hazard
identification
document
for
amitraz.

Table
1.
Acute
Toxicity
of
Amitraz
Guideline
No.
Study
Type
MRID
#(
s)
Results
Toxicity
Category
81­
1
Acute
Oral
00041539
LD
50:
531
mg/
kg
(
M)
515
mg/
kg
(
F)
III
81­
2
Acute
Dermal
00040862
LD
50:
>
200
mg/
kg
II
81­
3
Acute
Inhalation
00029963
LC
50:
2.4
mg/
L
III
81­
4
Primary
Eye
Irritation
00040861
Non­
irritating
IV
81­
5
Primary
Skin
Irritation
00040862
Non­
irritating
IV
81­
6
Dermal
Sensitization
­
G.
Pigs
00029965
Not
a
sensitizer
under
conditions
of
study
N/
A
1.4.2
Toxicological
Endpoints
The
March
17,
2004
report
of
the
Hazard
Identification
Assessment
Review
Committee
(
HIARC)
identified
toxicological
endpoints
of
concern
for
amitraz.
All
calculations
completed
in
this
document
are
based
on
the
most
current
toxicity
information
available
for
amitraz.
Endpoints
used
to
complete
this
assessment
are
presented
below
in
Table
2.
6
Table
2.
Summary
of
Toxicological
Dose
and
Endpoints
for
Amitraz
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
Special
FQPA
SF*
and
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
Acute
Dietary
(
General
population
including
infants
and
children)
NOAEL
=
0.25
mg/
kg/
day
UF
=
1000
Acute
RfD
=
0.00025
mg/
kg/
day
FQPA
SF
=
1
aPAD
=
acute
RfD
FQPA
SF
=
0.00025
mg/
kg/
day
Chronic
oral
study
in
the
dog
(
capsule)_
LOAEL
=
1.0
mg/
kg/
day
based
on
CNS
depression
during
the
first
two
days
of
dosing.

Chronic
Dietary
(
All
populations)
NOAEL=
0.25
mg/
kg/
day
UF
=
1000
Chronic
RfD
=
0.00025
mg/
kg/
day
FQPA
SF
=
1
cPAD
=
chronic
RfD
FQPA
SF
=
0.00025
mg/
kg/
day
Chronic
oral
study
in
the
dog
(
capsule)
LOAEL
=
1.0
mg/
kg/
day
based
on
CNS
depression
during
the
first
two
days
of
dosing.

Short­
and
Intermediate
­
Term
Incidental
Oral
(
1­
30
days
and
1­
6
months)
NOAEL=
0.25
mg/
kg/
day
Residential
LOC
for
MOE
=
1000
Occupational
=
NA
Chronic
oral
study
in
the
dog
(
capsule)
LOAEL
=
1.0
mg/
kg/
day
based
on
CNS
depression
during
the
first
two
days
of
dosing.

Dermal
(
All
Durations)
Oral
study
NOAEL=
0.25
mg/
kg/
day
(
dermal
absorption
rate
8%)
Residential
LOC
for
MOE
=
1000
Occupational
LOC
for
MOE
=
100
Chronic
oral
study
in
the
dog
(
capsule)
LOAEL
=
1.0
mg/
kg/
day
based
on
CNS
depression
during
the
first
two
days
of
dosing.

Inhalation
(
All
Durations)
Oral
study
NOAEL=
0.25
mg/
kg/
day
(
inhalation
absorption
rate
=
100%)
Residential
LOC
for
MOE
=
1000
Occupational
LOC
for
MOE
=
100
Chronic
oral
study
in
the
dog
(
capsule)
LOAEL
=
1.0
mg/
kg/
day
based
on
CNS
depression
during
the
first
two
days
of
dosing.

Cancer
(
oral,
dermal,
inhalation)
Q1*
=
2.83
x
10­
2
N/
A
Combined
hepatocellular
adenomas
and
carcinomas
in
female
mice.

UF
=
uncertainty
factor,
FQPA
SF
=
Special
FQPA
safety
factor,
NOAEL
=
no
observed
adverse
effect
level,
LOAEL
=
lowest
observed
adverse
effect
level,
PAD
=
population
adjusted
dose
(
a
=
acute,
c
=
chronic)
RfD
=
reference
dose,
MOE
=
margin
of
exposure,
LOC
=
level
of
concern,
NA
=
Not
Applicable
7
NOTE:
The
Special
FQPA
Safety
Factor
recommended
by
the
HIARC
assumes
that
the
exposure
databases
(
dietary
food,
drinking
water,
and
residential)
are
complete
and
that
the
risk
assessment
for
each
potential
exposure
scenario
includes
all
metabolites
and/
or
degradates
of
concern
and
does
not
underestimate
the
potential
risk
for
infants
and
children.

2.0
Incident
Reports
Animal
incident
reports
for
currently
registered
amitraz
products
from
1992
through
2003
were
reviewed.
In
general,
there
have
been
few
reports
of
amitraz
toxicity
in
recent
years.

The
most
notable
incidents
were
reports
of
dogs
pulling
a
tick
collar
off
another
dog
and
ingesting
the
collar.
This
has
resulted
in
serious
toxicity
including
bradycardia
and
depression,
resulting
in
emergency
veterinary
care.
Yohimbine
is
a
specific
antidote
for
amitraz
toxicity
in
dogs.

There
were
fewer
reports
for
toxicity
in
dogs
while
wearing
tick
collars,
including
weakness,
ataxia,
vomiting,
or
seizures.
These
reports
were
unverified.

There
were
3
reports
of
abortions
or
stillbirths
in
pigs
from
1992
­
1996.
These
reports
were
unverified.
There
were
several
reports
of
misuse
of
cattle/
pig
formulation
on
horses
or
dogs
resulting
in
death.

A
review
of
human
incident
data
is
pending
and
is
not
available
at
this
time.

3.0
Residential
Exposure
and
Risk
Estimates
One
applicator/
handler
scenario
and
three
post­
application
scenarios
were
identified
and
used
as
a
basis
for
HED's
residential
exposure
estimates.
Intermediate­
term
dermal
and
oral
MOEs
were
calculated
for
this
assessment.
The
scenarios
identified
and
examined
in
this
TRED:

­
Adult
residential
handler
(
applicator),
the
person
unwraps
the
collar
and
places
it
on
the
dog
­
dermal.

­
Toddler
­
dermal
(
post­
application)

­
Toddler
­
incidental
oral
(
post­
application)

­
Adult
­
dermal
(
post­
application)

A
target
MOE
of
1000
is
considered
adequate
for
Intermediate­
term
residential
exposure
via
dermal
routes.

In
this
TRED
HED
estimated
dermal
postapplication
cancer
risks
for
adults.
(
Cancer
risk
estimates
<
1
x
10­
6
are
not
of
concern.)
8
Although
HED
considers
the
residential
handler
scenario
as
having
potential
exposure
risk,
the
most
significant
exposure
of
concern
is
for
post­
application
scenarios
as
these
exposures
are
of
longer
duration
and
potentially
affect
more
sensitive
residents
including
infants
and
children.
Therefore
this
document
primarily
focuses
on
residential
post­
application
exposures
only,
and
does
not
address
residential
handlers.

3.1
Residential
Exposures
As
stated
above,
HED
considers
post­
application
exposure
to
residents,
including
children,
to
be
the
primary
concern
of
potential
exposure
to
amitraz
via
this
registered
use.
Residents
(
adults
and
children)
can
be
exposed
to
amitraz
via
it's
use
in
a
dog
collar.
Once
the
collar
is
applied
the
amitraz
residues
potentially
are
spread
throughout
the
surface
area
of
the
dog
exposing
residents
to
these
residues
by
dermal
contact
with
the
treated
dog.
Therefore,
HED
assessed
residential
post­
application
exposure
to
amitraz
via
it's
presence
in
the
collar
on
the
dog
and
thereby
potentially
spreading
throughout
the
fur
of
the
dog.
Identifying
toddlers
as
the
most
sensitive
of
potentially
exposed
residential
populations,
HED
conducted
two
assessments
based
on
likely
activities
for
a
toddler:
hugging
the
dog,
and
incidental
oral
ingestion
through
hand­
tomouth
actions
after
hugging
the
dog.
An
additional
assessment
for
adults,
based
on
hugging
the
dog
was
also
conducted.

Since
the
vapor
pressure
for
amitraz
=
3.4
x
10­
4
Pa
at
25

C,
and
as
such
is
considered
moderate,
HED
feels
that
there
is
potential
inhalation
exposure
as
a
certain
amount
of
off­
gassing
is
expected
to
occur.
However,
HED
did
not
address
inhalation
exposures
as
the
dermal
exposures
exceeded
HED's
levels
of
concern
and
data
concerning
inhalation
exposures
via
pet
collars
was
not
available.

3.2
Residential
Exposure
&
Risk
Estimates:
Post­
application
(
non­
cancer)

HED
considered
the
postapplication
exposure
in
the
residential
environment
to
amitraz
from
the
use
of
amitraz
treated
dog
collars.
For
this
home
use
scenario,
residential
risks
attributable
to
non­
dietary
ingestion
and
dermal
exposure
were
assessed
for
toddlers
and
adults
after
contact
with
treated
pets
based
on
the
guidance
provided
in
the
SOPs
for
Residential
Exposure
Assessment
(
U.
S.
EPA,
1997,
1999)
1,
and
also
Exposure
to
Children
and
Adults
to
Transferable
Chlorpyrifos
Residues
from
Dogs
Treated
with
Flea
Control
Collars
(
Boone,
J.
s.
et
al.
2001)
2.
Boone,
J.
et
al.
also
served
as
a
source
of
surrogate
data
for
transferrable
pesticide
residues
from
dog
fur.
To
this
date,
HED
has
received
no
chemical
specific
data
concerning
this
use
pattern
from
the
amitraz
registrant(
s).

The
dermal
contact
scenario
is
based
on
the
use
of
the
transferable
residue
data
normalized
by
the
sampling
area
and
by
the
amount
of
active
ingredient
in
the
collar
(
in
units
of

g/
cm2/
gram
ai).
A
linear
relationship
between
the
active
ingredient
and
the
residues
is
assumed.
The
transferable
residues
are
then
extrapolated
to
the
surface
area
of
a
"
hug"
(
i.
e.,
1875
cm2
­
toddlers).
No
data
are
available
to
determine
the
frequency
of
"
hugs".
However,
the
9
transferability
of
the
residues
from
the
5
minute
vigorous
petting
routine
in
the
study
is
a
reasonable
surrogate
for
the
transferability
of
a
days
worth
of
"
hugs"
of
a
dog
by
a
child.

No
defensible
rationale
is
available
to
determine
an
"
area"
weighted
mean
of
the
residues
from
the
neck
with
collar,
neck
without
collar,
and
back.
Therefore,
to
avoid
unnecessary
postulating
on
percentage
of
each
area
of
the
dog
hugged,
a
simplistic
use
of
proportions
(
i.
e.,
thirds)
of
the
three
monitored
areas
of
the
dog
has
been
selected.
That
is,
residues
measured
on
the
neck
of
the
dog
with
collar,
without
collar,
and
the
back
of
the
dog
from
1
to
168
days
after
treatment
(
DAT)
were
weighted
by
1/
3
each,
summed
and
averaged.
The
initial
4
­
hour
measurement
was
not
included
in
the
time­
weighted
average
(
TWA).
The
surrogate
value
to
be
used
as
the
dermal
TWA
transferable
residue
of
amitraz
is
0.29

g/
cm2/
gram
ai
(
or
0.29

g/
cm2/
gram
ai
x
1875
cm2
hug
=
540

g/
gram
ai).
This
represents
a
unit
daily
exposure
for
an
intermediate
to
chronic
duration.

The
traditional
estimates
of
hand­
to­
mouth
exposure
are
based
on
estimates
of
residues
on
a
child's
hand,
the
frequency
of
which
the
hand
goes
in
the
mouth,
and
the
duration
the
child
is
in
contact
with
the
treated
surface.
While
duration
estimates
are
available
for
a
child
playing
outside
(
e.
g.,
on
lawn),
no
estimates
of
contact
time
are
available
for
pets.
Therefore,
it
is
recommended
for
the
pet
collar
scenario
that
the
oral
hand­
to­
mouth
route
be
based
on
the
amount
of
residue
transferred
from
the
neck
with
the
collar
(
highest
of
the
three
areas
monitored).
The
residues
available
from
the
5
minute
vigorous
petting
routine
is
believed
to
be
a
conservative
estimate
of
the
amount
of
residue
available
for
ingestion
for
a
day.
It
is
believed
to
be
a
conservative
estimate
because
it
represents
7.5
seconds
of
petting
prior
to
each
of
40
hand­
tomouth
events
(
i.
e.,
(
5
minutes
sampling
x
60
seconds/
minute)
/
(
2
hours
per
day
x
20
hand­
tomouth
events
per
hour)).
The
two
hour
duration
is
arbitrary,
only
presented
as
a
point
of
reference.
Furthermore,
the
biological
monitoring
data,
even
though
inconclusive
for
regulatory
decisions,
do
not
indicate
any
dose
levels
higher
than
that
estimated
by
the
residue
method.
However,
more
research
is
needed
in
this
area
of
pet
collar
exposure.

Labels
for
the
impregnated
collars
states
efficacy
for
three
months,
therefore,
the
maximum
application
to
the
dog
would
be
four
times/
year.
The
net
weight
of
the
collar
is
42g
with
9.0%
amitraz
yields
3.8
g
active
ingredient
(
ai)
in
the
collar
(
EPA
Reg.
No.
2382­
170*).

A
series
of
assumptions
and
exposure
factors
served
as
the
basis
for
completing
intermediate­
term
homeowner
non­
cancer,
post­
application
risk
assessments.
Each
assumption
is
detailed
below:

S
The
average
body
weight
of
an
adult
used
in
all
assessments
is
70
kg.
For
toddler
assessments,
15
kg
weight
was
used
as
directed
by
SOPs
for
Residential
Exposure
Assessment.

S
The
amount
of
available
pesticide
on
the
dog's
fur
as
a
result
of
wearing
the
treated
collar
on
a
Time
Weighted
Average
(
TWA)
=
0.29
ug/
cm2
/
g
ai
as
a
transferable
unit
of
residue.
2
10
°
In
calculating
potential
post­
application
dermal
exposure
for
such
dog
related
activities
as
hugging,
HED
used
the
following
surface
areas
(
the
dermal
contact
area)
of
a
hug
to
a
dog:
toddler
=
1875
cm2;
adults
=
5625
cm2.1
Thus
the
equation
for
Estimated
Absorbed
Dermal
Dose
(
EADD)
exposure
postapplication
for
residents
becomes:

EADD
=
Transferable
residue
x
fraction
transferred
x
application
rate
x
dermal
absorption/
body
weight.

Thus
for
toddlers:

S
EADD
(
mg/
kg/
day)
=
(
0.29
ug/
cm2
/
g
ai)
x
0.001
mg/
ug
x
1875
cm2
x
(
3.8
g
ai
Amitraz
pet
collar)
x
Dermal
Absorption(
DA*)/
15
kg.

And,
the
equation
for
Estimated
Absorbed
Dermal
Dose
(
EADD)
exposure
postapplication
for
adults
becomes:

S
EADD
(
mg/
kg/
day)
=
(
0.29
ug/
cm2
/
g
ai)
x
0.001
mg/
ug
x
5625
cm2
x
(
3.8
g
ai
Amitraz
pet
collar)
x
Dermal
Absorption(
DA*)/
70
kg.

Toddler
Hand­
to­
Mouth
exposure
from
Residential
Exposures
Assessment
SOPs
was
calculated
as
follows:

Dose
(
mg/
kg/
day)
=
(
Dog's
neck
with
collar
of
1.5
ug/
cm2
/
gram
ai
x
3.8
gm
ai
Amitraz/
collar
x
0.001mg/
ug
x
0.5
saliva
extraction
efficiency
x
20
cm2
palmar
surface
area
of
fingers
into
mouth)*/
15
kg
body
weight.

Where:
*
Neck
with
collar
of
1.5

g/
cm2/
gram
ai
=
(
TWA
340

g
neck
with
collar/
88
cm2
child's
palm)
/
2.54
gram
ai
in
chlorpyrifos
test
collar.
[
child's
palm
surface
area
is
350
cm2
for
both
hands;
therefore,
175
cm2
represents
one
hand
and
88
cm2
represents
the
palm
of
one
hand].
Using
the
child's
hand
assumes
that
the
sampling
area
of
the
dog
(
258
cm2)
would
yield
the
same
amount
of
transferable
residue
regardless
if
the
hand
used
to
pet
the
dog
was
an
adult's
hand
(
as
monitored
in
the
study)
or
a
smaller
hand
of
a
child.

MOE
=
NOAEL
(
0.25
mg/
kg/
day)/
Estimated
Absorbed
Daily
Dose
(
EADD)

*
Dermal
Absorption
=
8.0%.

Table
3.
represents
the
calculated
residential
MOEs
for
various
activities
as
related
to
amitraz
treated
dog
collars.

Table
3.
Residential
Post­
Application
Intermediate­
Term
Risk
Estimates
Resident
Dog
Related
Activity
EADD
*
(
mg/
kg/
day)
MOE
11
Toddler
hugging
0.011
22
Toddler
hand
to
mouth
0.0038
65
Adult
hugging
0.007
35
*
EADD
=
Estimated
Absorbed
Dermal
Dose
MOE
=
NOAEL
(
0.25
mg/
kg/
day)/
Estimated
Absorbed
Dermal
Dose
3.3
Residential
Carcinogenic
Risk
Estimates:
Post­
Application
To
assess
carcinogenic
risk
for
amitraz
exposure
through
the
examined
use,
HED
selected
hugging
the
animal
as
the
most
likely
or
common
vector
of
concern
for
the
potential
exposure
over
the
course
of
a
lifetime.
HED
therefore
used
the
same
Estimated
Absorbed
Dermal
Dose
(
EADD)
described
above
in
the
non­
cancer
risk
estimates
and
extrapolated
over
a
70
year
lifetime,
using
high
and
low
end
lifetime
expectations
for
the
dog
(
10
and
20
years)
and
employing
the
following
assumptions:

S
The
dog
will
wear
the
treated
collar
throughout
it's
lifetime
(
estimated
for
10
and
20
years).

S
A
dog
owner
will
hug
his
or
her
dog
once
a
day
over
the
lifetime
of
the
dog.

S
As
in
the
case
of
post­
application
non­
cancer
estimates,
the
Time
Weighted
Average
(
TWA)
of
available
pesticide
on
the
dog's
fur
is
constant.

Hence,
the
equation
for
carcinogenic
risk
estimate
over
a
lifetime
for
the
examined
use,
utilizing
Q
1*
method
becomes:

­
LADD
(
Lifetime
Average
Daily
Dose)
=
(
EADD)
x
(
number
hugs/
year)
x
(
number
of
years
of
pet
ownership/
70
year
lifetime).

S
Carcinogenic
Risk
=
(
LADD)
x
(
Q
1*),
where
Q
1*
=
2.83
x
10E­
2
(
mg/
kg/
day
E­
1)
(
Memorandum
February
11,
2004).

The
following
table
represents
the
numerical
risk
estimation
for
carcinogenic
residential
handler
risk
associated
with
application
of
pet
collars
impregnated
with
amitraz.

Table
4
:
Residential
Post­
Application
Carcinogenic
Risk
Assessment
Over
a
Lifetime
Estimated
Lifetime
of
Treated
Dog
Estimated
Absorbed
Daily
Dosea
(
mg/
kg/
day)
Amortization
LADDb
(
mg/
kg/
day)
Carcinogenic
Riskc
(
mg/
kg/
day)
12
#
of
Days
Exposed
/
Year
Years
of
lifetime
(
70
yrs)

10
years
0.007
365
10/
70
0.
001
2.8
e
­
5
20
years
0.007
365
20/
70
0.002
5.6
e
­
5
a.
Estimated
Absorbed
Daily
Dermal
Dose
is
from
Table
3.

b.
LADD
(
lifetime
average
daily
dose)
=
(
absorbed
dermal
dose)
x
(
number
of
days
exposed/
365days)
x
(
number
of
years
of
pet
ownership/
70
year
lifetime)

c.
Carcinogenic
Risk
=
(
LADD)*(
Q
1
*),
where
the
Q
1
*,
is
2.83
x
10E­
2
(
mg/
kg/
day)­
1
References
13
1.
U.
S.
EPA
(
1999)
Overview
of
Issues
Related
to
The
Standard
Operating
Procedures
For
Residential
Exposure
Assessment,
Health
Effects
Division
of
the
Office
of
Pesticide
Programs
[
Presented
to
the
FIFRA
SAP
in
September
1999]

U.
S.
EPA
(
1997)
Standard
Operating
Procedures
for
Residential
Exposure
Assessment,
Health
Effects
Division
of
the
Office
of
Pesticide
Programs
2.
Boone,
J.
S.:
Chambers,
J.
E.;
and
Tyler,
J.
W.,
(
2001),
Transferable
Residues
From
Dog
Fur
and
Plasma
Cholinesterase
Inhibition
in
Dogs
Treated
with
a
Flea
Control
Dip
Containing
Chlorpyrifos,
Environmental
Health
Perspectives,
Volume
109,
Number
11,
November
2001.

Boone,
J.
S.:
Chambers,
J.
E.;
and
Tyler,
J.
W.,
(
2001)
Exposure
to
Children
and
Adults
to
Transferrable
Residues
Chlorpyrifos
from
Dogs
Treated
with
Flea
Control
Collars,
Presented
at
International
Society
of
Exposure
Analysis
Meeting,
2001.

.