Document ID: EPA-HQ-OPP-2004-0048-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2004-06-18T04:00Z

1
Amitraz
Risk
Assessment
Overview
Introduction
This
document
summarizes
EPA's
human
health
and
environmental
fate
risk
findings
for
the
pesticide
amitraz.
These
findings
are
presented
fully
in
the
HED
human
health
risk
assessment
document
"
Amitraz:
Human
Health
Risk
Assessment"
dated
April
29,
2004;
and
the
EFED
water
assessment
document
"
Revised
Amitraz
Drinking
Water
Assessment
for
Tolerance
Reassessment
Eligibility
Decision
(
TRED)",
dated
May
1,
2004.

In
a
recent
letter
to
the
Agency,
Bayer
CropScience
(
BCS)
requested
cancellation
for
the
wettable
powder
(
WP)
registrations
of
Ovasyn
Insecticide/
Miticide
(
EPA
Reg.
No.
264­
625)
and
Mitac
W
Insecticide
(
EPA
Reg.
No.
264­
636).
The
registrant
also
requested
to
revoke
established
tolerances
for
apples,
beeswax,
cotton
(
US
cotton
registration
is
being
voluntarily
revoked),
honey,
and
pears,
but
to
maintain
import
tolerances
for
hops
and
cottonseed.

In
response
to
the
request
by
the
registrant
to
voluntarily
withdraw
certain
registrations
and
revoke
tolerances
of
various
commodities,
the
Agency
published
a
6(
f)
notice
relative
to
their
request.
A
30
day
public
comment
period
was
published
and
no
comments
were
received.
Therefore,
a
cancellation
order
will
be
issued
in
the
near
term
effectively
cancelling
registrations
(
EPA
No.
264­
625
and
264­
636)
and
proposing
tolerance
revocation
for
apples,
beeswax,
cotton,
honey,
and
pears.
Herein,
all
references
of
risk
associated
with
amitraz
will
be
attributed
to
those
registrations
for
use
on
beef
and
dairy
cattle,
swine
and
dogs.

The
purpose
of
this
overview
is
to
assist
the
reader
in
understanding
the
conclusions
reached
in
the
risk
assessments
by
identifying
the
key
features
and
findings
of
each.

Use
Profile
$
Insecticide:
Amitraz
is
an
insecticide/
acaricide
with
registered
food/
feed
uses
in
the
U.
S.
on
beef
and
dairy
cattle,
and
hogs.
However,
as
previously
noted,
the
registrant
has
requested
to
revoke
all
tolerances
for
Section
3
registrations
except
for
beef
and
dairy
cattle
and
hogs
as
well
as
import
tolerances
for
hops
and
cottonseed.
Amitraz
is
also
registered
for
use
on
dogs.
2
$
Targeted
Pest:
Registered
products
containing
amitraz
are
intended
for
application
on
beef
cattle,
dairy
cattle
and
swine
for
mite,
tick
and
lice
management
and
for
tick
and
flea
control
on
dogs.

$
Formulations:
Amitraz
is
formulated
as
an
emulsifiable
concentrate
(
12.5
percent
active
ingredient),
1.5
lb/
gal
soluble
concentrate
(
SC),
and
impregnated
collars
(
9
percent
active
ingredient).
The
emulsifiable
concentrate
(
EC)
formulations
are
registered
for
use
on
cattle
and
swine
as
dermal
treatments.
The
impregnated
collars
are
registered
for
use
on
dogs.
Amitraz
was
previously
registered
as
a
wettable
powder
(
50
and
19.8
percent
active
ingredient)
for
use
on
pears
and
cotton,
but
has
since
been
voluntarily
cancelled.

$
Method
of
Application:
For
mite,
tick
and
lice
management
on
beef
and
dairy
cattle,
the
EC
formulation
(
Taktic
E.
C.)
may
be
applied
twice
as
a
0.05%
a.
i.
spray,
with
a
7­
day
retreatment
interval
and
no
pre­
slaughter
interval
(
PSI).
For
use
on
swine,
Taktic
E.
C.
is
not
to
be
applied
within
three
days
of
slaughter,
and
swine
are
to
be
treated
no
more
than
four
times
per
year.
For
amitraz
use
on
beef
cattle,
dairy
cattle
and
swine,
the
following
application
methods
are
suggested:
1)
cattle
applied
via
spraying
or
by
a
spray
dip
machine,
2)
swine
applied
via
spraying,
and
3)
piglets/
weaners
applied
by
dipping.

For
dogs,
the
tick
and
flea
collars
(
Preventic
and
Preventic
Plus),
can
be
applied
every
three
months
in
dogs
more
than
12
weeks
of
age.

$
Use
Summary:
Based
on
Agency
data,
the
total
annual
usage
of
amitraz
on
livestock
is
10,000
pounds
per
year
with
7,000
pounds
accounted
for
by
livestock
(
includes
hogs)
whereby
beef
and
dairy
cattle
account
for
the
remaining
3,000
pounds
of
usage.
The
annual
average
of
nonagricultural
usage
of
amitraz
is
estimated
at
4,000
pounds
a.
i.
and
is
used
solely
for
control
of
fleas
and
ticks
on
dogs.

$
Technical
Registrant:
Bayer
CropScience.
3
Human
Health
Risk
Assessment
The
toxicology
database
for
Amitraz
is
inadequate,
due
to
the
presence
of
several
major
data
gaps.
The
available
studies
are
not
of
the
most
current
quality;
however,
sufficient
data
may
be
collected
from
them
for
use
in
an
assessment
of
risk
to
human
health.
The
toxicity
profile
for
Amitraz
cannot
be
completely
characterized
for
all
effects,
especially
those
relating
to
developmental,
reproductive
and
neurotoxic
effects.

Amitraz
is
not
stable
in
the
diet
and
the
current
toxicological
endpoints
for
risk
assessment
are
based
on
a
capsule
or
bolus
dose
study.
The
dermal
and
inhalation
endpoints
are
also
based
on
the
capsule
study
(
see
Table
1
below).
Humans
are
more
likely
to
be
exposed
to
the
parent
via
the
dermal
and
inhalation
and
non­
dietary
oral
routes
associated
with
livestock
and
pet
uses
rather
than
dietary
exposures.

Table
1:
SUMMARY
OF
TOXICOLOGY
ENDPOINT
SELECTION
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
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.
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
Special
FQPA
SF*
and
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
4
Dermal
(
All
Durations)
Oral
NOAEL=
0.25
mg/
kg/
day
(
dermal
absorption
rate
8%)
Residential
LOC
MOE
=
1000
Occupational
LOC
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
NOAEL=
0.25
mg/
kg/
day
(
inhalation
absorption
rate
=
100%)
Residential
LOC
MOE
=
1000
Occupational
LOC
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
Group:
C
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
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.

The
Hazard
Identification
Assessment
Review
Committee
(
HIARC)
determined
that
the
special
FQPA
safety
factor
should
be
reduced
to
1X;
however,
a
10X
database
uncertainty
factor
(
UF
DB)
is
required
due
to
an
incomplete
database
(
i.
e.
lack
of
acceptable
rabbit
developmental
toxicity
and
two­
generation
reproduction
studies).
Based
on
the
weight
of
evidence
presented,
there
is
concern
for
potential
reproductive
effects
and
neurotoxicity
in
developing
fetuses.
Therefore,
the
Agency
is
requiring
a
combined
2­
generation
reproduction
study
in
the
rat
with
components
assessing
for
potential
developmental
and
adult
neurotoxicity.

The
10X
UF
DB
is
applied
to
dietary
(
acute
and
chronic)
and
non­
dietary/
residential
(
incidental
oral,
dermal
and
inhalation)
risk
assessments
because
the
required
studies
may
provide
endpoints
applicable
for
risk
assessments.
Therefore,
a
total
UF
of
1000
has
been
applied
to
all
dietary
and
residential
risk
assessments.

Acute
Dietary
(
Food)
Risk
Acute
dietary
risk
is
calculated
considering
the
toxicity
of
a
chemical,
what
is
eaten
by
individuals
in
one
day
and
residue
values
for
various
foods.
A
risk
estimate
that
is
less
than
100%
of
the
acute
Population
Adjusted
Dose
(
aPAD)
(
the
dose
at
which
an
individual
could
be
exposed
on
any
given
day
and
no
adverse
health
effects
would
be
expected)
does
not
exceed
the
Agency's
risk
concern.
5
Refined
probabilistic
acute
risk
assessment
was
conducted
using
the
Lifeline
Model
(
Version
2.0)
which
uses
food
consumption
data
from
the
United
States
Department
of
Agriculture's
(
USDA's).
Continuing
Surveys
of
Food
Intakes
by
Individuals
(
CSFII)
from
1994­
1996
and
1998.
Acute
exposure
estimates
were
based
on
data
from
dermal
metabolism
studies
provided
by
the
registrant
and
percent
crop
treated
provided
by
the
Biological
and
Economic
Analysis
Division
(
BEAD).

°
Acute
dietary
risks,
using
Lifeline
 
Model,
are
above
HED's
level
of
concern
for
children
1­
2
yrs
(
186%
of
aPAD,
0.000465
mg/
kg/
day)
and
children
3­
5
years
old
(
170%
of
aPAD,
0.000425
mg/
kg/
day)
at
the
99.9th
percentile
of
exposure.
For
all
other
populations,
exposure
was
below
65%
of
the
aPAD
at
the
99.9th
percentile.

°
Even
though
beef
and
pork
provide
relatively
low
exposure,
milk
continues
to
provide
exposure
at
the
99.9th
percentile
even
with
the
low
percent
crop
treated
due
to
the
application
of
residues
to
the
three
milk
components
(
water,
fat,
non­
fat
solids),
and
the
relatively
high
percent
of
toddlers
that
consume
milk.

Chronic
and
Cancer
Dietary
(
Food)
Risk
Chronic
dietary
risk
is
calculated
by
using
the
average
consumption
value
for
food
and
average
residue
values
on
those
foods
over
a
70­
year
lifetime.
A
risk
estimate
that
is
less
than
100%
of
the
chronic
RfD
(
the
dose
at
which
an
individual
could
be
exposed
over
the
course
of
a
lifetime
and
no
adverse
health
effects
would
be
expected)
does
not
exceed
the
Agency's
risk
concern.
Estimated
chronic
dietary
risk
is
below
the
Agency's
level
of
concern
for
all
populations
(<
1%
of
cPAD).
The
estimated
exposure
to
all
populations
to
amitraz
is
<
0.000001
mg/
kg/
day
for
both
dietary
risk
assessment
models.
Applying
the
Q
1*
of
2.83
x
10­
2
(
mg/
kg/
day)­
1
to
the
exposure
value
results
in
a
cancer
risk
estimate
of
2.8
x
10­
8.
Therefore,
estimated
cancer
dietary
risk
from
food
alone
is
below
the
Agency's
level
of
concern.

Drinking
Water
Dietary
Risk
Drinking
water
exposure
to
pesticides
can
occur
through
groundwater
and
surface
water
contamination.
EPA
considers
both
acute
(
one
day)
and
chronic
(
multiple
year)
drinking
water
risks,
and
uses
either
modeling
or
actual
monitoring
data,
if
available,
to
estimate
those
risks.
Modeling
is
carried
out
in
tiers
of
further
refinement,
but
is
designed
to
provide
a
high­
end
estimate
of
exposure.
To
determine
the
maximum
allowable
contribution
from
water
allowed
in
the
diet,
EPA
first
calculates
the
overall
allowable
risk
and
subtracts
the
amount
contributed
by
food
to
determine
a
"
drinking
water
level
of
comparison"
(
DWLOC).
This
is
then
compared
to
estimated
concentrations
in
water
to
ascertain
whether
modeled
or
monitoring
levels
in
water
exceed
this
level
of
risk.
6
Surface
water
EEC:
Typical
Estimate:
Peak
Concentration
=
0.1
ppb;
Annual
Average
Concentration
=
0.0006
ppb
Groundwater
EEC:
Typical
=
0.000009
ppb
The
assessment
assumed
30
percent
of
the
U.
S.
production
volume
for
use
on
swine
is
used
in
a
single
watershed
in
North
Carolina.
Based
on
the
assumption
that
all
amitraz
would
be
used
in
this
watershed,
the
"
typical"
scenario
may
represent
the
most
probable
use
scenario
and
would
likely
exceed
monitoring
data
on
a
annual
average
basis.
This
assumption
is
based
on
the
short
half­
life
of
the
compound
in
the
natural
environment,
the
reactive
nature
of
the
compound
in
acidic
environments
typical
of
the
Southeast,
and
a
substantial
portion
of
the
product
must
remain
on
the
target
site
in
order
to
be
effective.

Amitraz
is
classified
as
a
Group
C
possible
human
carcinogen
and
it
has
a
Q*
of
2.83
x
10­
2.
Estimated
cancer
dietary
risk
from
food
and
water
is
below
HED's
level
of
concern.

Residential
Risk
The
Health
Effects
Division
(
HED)
considers
the
residential
risk
assessment
to
be
based
on
highend
estimates
of
exposure
generated
from
screening­
level
procedures
outlined
in
the
SOPs
for
Residential
Exposure
Assessment
(
U.
S.
EPA,
1997,
1999).
As
such,
the
risk
estimates
associated
with
pet
collars
are
conservative;
thereby,
largely
driven
by
default
assumptions
and
uncertainties
in
the
toxicity
database.

Although
there
is
potential
exposure
risk
for
residential
handler
scenarios,
EPA
has
decided
to
focus
on
post­
application
scenarios.

Post­
Application
Risk
Estimates
The
most
significant
exposure
of
concern
is
for
residential
post­
application
via
current
registered
uses.
These
exposures
are
of
longer
duration
and
can
potentially
affect
more
sensitive
residents
such
as
infants
and
children.
As
such,
risks
were
estimated
for
post­
application
dermal
exposures
of
adults,
and
dermal
and
incidental
oral
exposures
of
children
for
non­
cancer
effects,
and
cancer
effects
from
dermal
exposures
of
adults,
only.

The
toxicological
endpoints
of
concern
(
for
short
and
intermediate
term
dermal
and
inhalation
7
exposures,
and
incidental
exposures)
are
a
NOAEL
of
0.25
mg/
kg/
day
with
a
LOAEL
of
1.0
mg/
kg/
day.
These
were
selected
from
a
chronic
oral
study
based
on
CNS
depression
during
the
first
two
days
of
dosing.
A
dermal
absorption
factor
of
8.0%
is
applied
for
dermal
exposure
for
route
to
route
extrapolation.

The
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.
Intermediate­
term
dermal
and
oral
MOEs
were
calculated
for
the
risk
assessment.
A
target
MOE
of
1000
is
considered
adequate
for
intermediate­
term
residential
exposure
via
dermal
and
oral
routes.
HED
also
estimated
dermal
postapplication
cancer
risks
for
adults
(
See
Tables
2&
3
below).

All
post­
application
scenarios
resulted
in
MOEs
which
exceed
HED's
level
of
concern
(
See
Table
2
below).

Table
2:
Residential
Post­
Application
Intermediate­
Term
Risk
Estimates
Resident
Dog
Related
Activity
EADD
*
(
mg/
kg/
day)
MOE
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
Table
3:
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)
#
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
2.
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
8
Aggregate
Risk
Acute
aggregate
risk
estimates
will
not
be
conducted
since
the
dietary
acute
risk
exceeds
HEDs
level
of
concern.
Short­
and
Intermediate­
Term
and
cancer
aggregate
risk
estimates
will
not
be
conducted
since
the
post
application
residential
exposure
scenarios
exceed
HED's
level
of
concern.

Chronic
aggregate
risk
estimates
associated
with
exposure
to
amitraz
residues
in
food
and
water
do
not
exceed
HED's
level
of
concern.
The
chronic
risk
estimates
are
below
the
Agency's
level
of
concern
for
the
general
U.
S.
population
and
all
population
subgroups
Occupational
Risk
Short­
Term
and
Intermediate­
Term
Handler
Risks
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
the
risk
assessment
primarily
focuses
on
residential
post­
application
exposures
only,
and
does
not
address
residential
handlers.

Summary
of
Pending
Data
Toxicology
870.3700:
Prenatal
developmental
toxicity
study
in
rabbits
870.3800:
A
two­
generation
reproduction
study
which
should
be
MODIFIED
to
include:

°
Due
to
the
concern
for
the
lack
of
stability
of
the
test
material
in
the
diet,
treatment
should
be
via
oral
(
gavage)
administration.
°
The
potential
for
neurotoxicity
in
the
developing
fetuses
should
be
evaluated
according
to
the
OPPTS
Guideline
§
870.6300.
°
The
potential
for
neurotoxicity
in
adults
should
be
evaluated
according
to
the
OPPTS
Guideline
§
870.6200.

Product
Chemistry
830.7050:
UV/
Visible
absorption
°
Data
are
required
for
the
UV/
absorption
of
the
PAI
(
Bayer
CropScience
97%
T).
9
Residue
Chemistry
Provided
that
the
registered
uses
on
cotton
and
pears
are
cancelled,
there
are
no
residue
chemistry
deficiencies
pertaining
to
amitraz
reregistration.
Additionally,
the
registrant
has
indicated
that
they
would
like
to
keep
the
cotton
tolerance
as
an
import
tolerance.

The
registrant
will
need
to
submit
a
formal
request
to
the
Agency
for
establishment
of
the
cottonseed
tolerance
as
an
import
tolerance,
and
information
about
the
use
pattern
in
foreign
countries,
and
residue
data
from
those
countries
in
order
to
support
the
request.

Non­
Dietary
Exposure
875.2400
Dermal
Exposure
Study
Non­
Guideline
Dog
Fur
Residue
Study