Document ID: EPA-HQ-OPP-2005-0230-0003
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2005-10-18T04:00Z

Page
1
of
59
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
Date:
09/
29/
2005
MEMORANDUM
SUBJECT:
Tau­
fluvalinate:
Revised
HED
Chapter
of
the
Reregistration
Eligibility
Decision
Document
(
RED).
PC
Code:
109302,
Case
#:
2295,
DP
Barcode:
D321911.

Regulatory
Action:
Phase
2
Reregistration
Action
Risk
Assessment
Type:
Single
Chemical
Aggregate
FROM:
Susan
Stanton,
Environmental
Scientist
Reregistration
Branch
3
Health
Effects
Division
(
7509C)

AND
John
Doherty,
Toxicologist
Jose
Morales,
Chemist
Robert
Travaglini,
Chemist
Reregistration
Branch
3
Health
Effects
Division
(
7509C)

THROUGH:
Catherine
Eiden,
Chief
Reregistration
Branch
3
Health
Effects
Division
(
7509C)

TO:
Kylie
Rothwell,
Chemical
Review
Manager
Reregistration
Branch
III
SRRD
(
7508C)

The
attached
risk
assessment
for
tau­
fluvalinate
has
been
revised
to
correct
errors
noted
in
the
registrant's
30­
day
error
comments
on
EPA's
preliminary
risk
assessment,
submitted
by
Wellmark
International
on
May
31,
2005.
Page
2
of
59
Table
of
Contents
1.0
Executive
Summary
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
4
2.0
Ingredient
Profile
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
6
2.1
Summary
of
Registered/
Proposed
Uses
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
7
2.2
Structure
and
Nomenclature
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
8
2.3
Physical
and
Chemical
Properties
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
9
3.0
Metabolism
Assessment
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
10
3.1
Comparative
Metabolic
Profile
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
10
3.2
Nature
of
the
Residue
in
Foods
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
11
3.2.1.
Description
of
Primary
Crop
Metabolism
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
11
3.2.2
Description
of
Livestock
Metabolism
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
11
3.2.3
Description
of
Rotational
Crop
Metabolism,
including
identification
of
major
metabolites
and
specific
routes
of
biotransformation
.
.
.
.
.
.
.
.
.
.
12
3.3
Environmental
Degradation
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
12
3.4
Toxicity
Profile
of
Major
Metabolites
and
Degradates
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
13
3.5
Summary
of
Residues
for
Tolerance
Expression
and
Risk
Assessment
.
.
.
.
.
.
.
.
13
3.5.1
Tabular
Summary
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
13
3.5.2
Rationale
for
Inclusion
of
Metabolites
and
Degradates
.
.
.
.
.
.
.
.
.
.
.
.
.
13
4.0
Hazard
Characterization/
Assessment
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
14
4.1
Hazard
Characterization
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
14
4.2
FQPA
Hazard
Considerations
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
20
4.2.1
Adequacy
of
the
Toxicity
Data
Base
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
20
4.2.2
Evidence
of
Neurotoxicity
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
20
4.2.3
Developmental
Toxicity
Studies
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
23
4.2.4
Reproductive
Toxicity
Study
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
25
4.2.5
Additional
Information
from
Literature
Sources
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
26
4.2.6
Pre­
and/
or
Postnatal
Toxicity
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
26
4.2.6.1
Determination
of
Susceptibility
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
26
4.2.6.2
Degree
of
Concern
Analysis
and
Residual
Uncertainties
for
Pre
and/
or
Post­
natal
Susceptibility
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
26
4.3
Recommendation
for
a
Developmental
Neurotoxicity
Study
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
27
4.3.1
Evidence
that
supports
requiring
a
Developmental
Neurotoxicity
study
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
27
4.3.2
Evidence
that
supports
not
requiring
Developmental
Neurotoxicity
study
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
28
4.3.2.1
Rationale
for
the
UF
DB
(
when
a
DNT
is
recommended)
.
28
4.4
Hazard
Identification
and
Toxicity
Endpoint
Selection
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
28
4.4.1
Acute
Reference
Dose
(
aRfD)
­
General
Population
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
29
4.4.2
Acute
Reference
Dose
(
aRfD)
­
Females
age
13­
49
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
30
4.4.3
Chronic
Reference
Dose
(
cRfD)
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
30
Page
3
of
59
4.4.4
Incidental
Oral
Exposure
(
Short
and
Intermediate
Term)
.
.
.
.
.
.
.
.
.
.
.
.
31
4.4.5
Dermal
Absorption
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
31
4.4.6
Dermal
Exposure
(
Short,
Intermediate
and
Long
Term)
.
.
.
.
.
.
.
.
.
.
.
.
31
4.4.7
Inhalation
Exposure
(
Short,
Intermediate
and
Long
Term)
.
.
.
.
.
.
.
.
.
.
31
4.4.8
Margins
of
Exposure
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
32
4.4.9
Recommendation
for
Aggregate
Exposure
Risk
Assessments
.
.
.
.
.
.
.
.
32
4.4.10
Classification
of
Carcinogenic
Potential
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
32
4.5
Special
FQPA
Safety
Factor
.
.
.
.
.
.
.
.
.
33
4.6
Endocrine
disruption
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
34
5.0
Public
Health
Data
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
35
5.1
Incident
Reports
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
35
5.2
Other
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
35
6.0
Exposure
Characterization/
Assessment
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
35
6.1
Dietary
Exposure/
Risk
Pathway
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
35
6.1.1
Residue
Profile
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
35
6.1.2
Acute
and
Chronic
Dietary
Exposure
and
Risk
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
37
6.2
Water
Exposure/
Risk
Pathway
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
38
6.3
Residential
(
Non­
Occupational)
Exposure/
Risk
Pathway
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
39
6.3.1
Residential
Handler
Exposure/
Risk
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
40
6.3.2
Residential
Post­
Application
Exposure/
Risk
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
40
6.3.3
Other
(
Spray
Drift,
etc.)
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
40
7.0
Aggregate
Risk
Assessments
and
Risk
Characterization
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
40
7.1
Acute
Aggregate
Risk
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
41
7.2
Short­
Term
Aggregate
Risk
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
41
7.3
Intermediate­
Term
Aggregate
Risk
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
41
7.4
Long­
Term
Aggregate
Risk
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
41
7.5
Cancer
Risk
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
41
8.0
Cumulative
Risk
Characterization/
Assessment
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
42
9.0
Occupational
Exposure/
Risk
Pathway
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
42
9.1
Short/
Intermediate/
Long­
Term
Handler
Risk
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
42
9.2
Short/
Intermediate/
Long­
Term
Postapplication
Risk
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
49
10.0
Data
Needs
and
Label
Requirements
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
50
10.1
Toxicology
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
50
10.2
Residue
Chemistry
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
50
10.3
Occupational
and
Residential
Exposure
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
50
References:
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
50
Appendices
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
51
Page
4
of
59
1.0
Executive
Summary
The
Health
Effects
Division
(
HED)
of
EPA's
Office
of
Pesticide
Programs
has
evaluated
the
toxicity
and
exposure
data
bases
for
the
pesticide
active
ingredient
tau­
fluvalinate
and
has
conducted
a
human
health
risk
assessment
in
support
of
the
Reregistration
Eligibility
Decision
(
RED)
for
this
active
ingredient.

Use
Information
Tau­
fluvalinate
is
an
insecticide/
miticide
in
the
pyrethroid
class
of
pesticides.
It
acts
as
an
axonic
poison
by
interfering
with
the
sodium
channels
of
both
the
peripheral
and
central
nervous
systems,
stimulating
repetitive
nervous
discharges,
leading
to
paralysis.
It
is
registered
for
a
single
food
use
(
beehives/
honey)
and
several
non­
food
uses,
including
ornamentals
(
outdoor
and
containergrown
greenhouse,
interior
plantscapes,
dip
for
cuttings),
building
surfaces/
perimeters,
ant
mounds
and
certain
crops
(
carrots
and
Brassica/
cole
crops)
grown
for
seed.
Tau­
fluvalinate
has
very
limited
annual
domestic
usage,
with
the
majority
of
this
usage
in
commercial
greenhouses
and
on
outdoor
field­
and
container­
grown
ornamentals.

Toxicology
The
available
toxicity
data
on
tau­
fluvalinate
are
adequate
to
assess
the
chemical's
hazard
potential.
Tau­
fluvalinate
is
a
pyrethroid
insecticide
of
the
type
II
class.
It
is
moderately
acutely
toxic,
having
been
classified
in
Toxicity
Category
II
by
the
oral
route
of
exposure
and
Category
III
by
the
dermal
route.
It
is
not
a
primary
irritant
to
either
the
eye
(
Toxicity
Category
III)
or
skin
(
Toxicity
Category
IV)
and
is
not
a
dermal
sensitization
agent.
The
principle
systemic
effects
seen
in
subchronic
and
chronic
studies
include
reductions
in
body
weight/
body
weight
gain
(
dogs
and
rats),
liver
weight
changes
(
dogs
and
rats)
and
chronic
nephritis
(
mouse).

Tau­
fluvalinate
is
a
pyrethroid
insecticide
that
acts
on
the
nervous
system
in
insects.
The
mammalian
studies
demonstrate
typical
clinical
signs
associated
with
pyrethroid
neurotoxicity,
including
excessive
grooming,
bulging
eyes,
abnormal
stance,
ruffled
fur,
hyperactivity,
salivation,
ataxia,
muscle
spasms,
tremors,
gait
abnormalities,
startle
response
hyperreaction
and
more.
Some
evidence
of
nerve
degeneration
was
seen
at
higher
doses
in
the
acute
neurotoxicity
study.

As
a
type
II
pyrethroid,
tau­
fluvalinate
causes
the
"
pyrethroid
reaction",
a
specific
type
of
dermal
irritation
following
contact.
The
"
pyrethroid
reaction"
may
be
one
manifestation
of
the
chemical's
ability
to
act
on
nerve
endings.
The
"
pyrethroid
reaction"
is
unlike
the
primary
dermal
irritation
assessed
in
acute
or
subchronic
dermal
irritation
studies.
It
occurs
during
animal
feeding
studies
when
dermal
contact
is
made
with
the
feed
and
may
result
in
early
termination
of
such
studies
for
humane
reasons
due
to
the
severity
of
skin
lesions
and
subsequent
infection.
Thus,
more
definitive
subchronic
and
chronic
studies
were
done
by
gavage.
In
humans,
the
pyrethroid
reaction
is
characterized
by
tingling
sensations
and/
or
itching,
often
severe,
upon
contact
with
the
chemical.

The
rat
developmental
toxicity
study
did
not
demonstrate
developmental
toxicity
at
the
highest
dose
tested.
The
rabbit
developmental
toxicity
demonstrated
some
signs
of
skeletal
variations
Page
5
of
59
(
curved
tibia
and
fibula)
but
at
the
same
dose
where
maternal
toxicity
was
seen.
There
were
no
effects
of
tau­
fluvalinate
on
reproductive
performance.
The
offspring
were
noted
to
have
tremors
in
one
generation
and
to
have
slight
body
weight
decrease
in
another
generation,
but
these
effects
occurred
at
a
dose
that
was
also
toxic
to
the
parents.
There
is
no
quantitative
or
qualitative
evidence
of
increased
susceptibility
of
rat
or
rabbit
fetuses
after
in
utero
and/
or
postnatal
exposure
to
tau­
fluvalinate
in
the
developmental
and
reproduction
studies.
Dose­
response
relationships
are
well­
characterized
and
clear
NOAELs/
LOAELs
have
been
identified
for
the
critical
effects.
Therefore,
the
special
FQPA
safety
factor
can
be
reduced
to
1X,
since
the
degree
of
concern
is
low
and
there
are
no
residual
uncertainties
for
pre­
and/
or
postnatal
toxicity.

No
evidence
of
carcinogenicity
was
seen
in
mice
or
rats,
and
there
is
no
concern
for
mutagenicity.
Tau­
fluvalinate
was
negative
for
mutagenic
effects
in
a
battery
of
tests,
including
reverse
mutation
in
Salmonella
typhimurium,
sister
chromatid
exchange
in
CHO
cells,
mouse
lymphoma
mutagenic
assay,
mammalian
cells
in
culture
transformation
assay
and
unscheduled
DNA
synthesis
in
rat
hepatocytes.

Residue
Chemistry
Tau­
fluvalinate
is
registered
for
a
single
food
use
in
beehives.
The
available
residue
chemistry
data
are
adequate
to
assess
human
dietary
exposure
to
tau­
fluvalinate
from
the
consumption
of
honey
from
treated
hives.
The
residue
of
concern
in
honey
for
both
tolerance
enforcement
and
risk
assessment
is
tau­
fluvalinate
per
se.
A
GC/
ECD
method
is
available
for
the
enforcement
of
tolerances
for
residues
of
tau­
fluvalinate
in
honey.

Environmental
Fate
The
available
environmental
fate
data
for
tau­
fluvalinate
are
adequate
to
assess
the
residues
of
concern
in
drinking
water.
Tau­
fluvalinate
is
highly
immobile
and
practically
insoluble
in
water,
indicating
a
low
potential
for
significant
residues
in
drinking
water.
None
of
the
major
degradates
found
in
environmental
fate
studies
are
of
toxicological
concern.
Therefore,
the
residue
of
concern
in
drinking
water
is
tau­
fluvalinate,
per
se.

Residential
Exposure
Although
tau­
fluvalinate
is
labeled
for
use
in
residential
areas,
a
residential
exposure
assessment
was
not
conducted,
since
there
is
little
potential
for
residential
exposure
from
these
uses.
There
are
no
homeowner
applications
allowed
and,
therefore,
no
potential
for
residential
handler
exposure.
Also,
there
are
no
wide
area,
broadcast
applications
of
tau­
fluvalinate
in
residential
areas
and,
therefore,
little
potential
for
post­
application
residential
exposure.
The
current
residential
uses
(
building
surfaces/
perimeters
and
ant
mounds)
are
largely
spot
applications
that
are
not
likely
to
result
in
significant
post­
application
exposure
of
adults
or
children.
Page
6
of
59
Aggregate
Risk
Acute
and
chronic
(
long­
term)
aggregate
risk
assessments
were
conducted
for
tau­
fluvalinate.
These
assessments
considered
dietary
(
food
+
water)
exposure
only,
since
the
current
uses
of
taufluvalinate
are
not
expected
to
result
in
significant
residential
exposure.

Tier
1acute
and
chronic
dietary
exposure
analyses
using
both
DEEM­
FCID
 
and
Lifeline
indicate
that
aggregate
exposure
to
tau­
fluvalinate
from
food
and
drinking
water
is
well
below
HED's
levels
of
concern
for
this
pesticide.
Estimated
chronic
exposures
are
less
than
1%
of
the
cPAD
for
the
general
U.
S.
population
and
all
population
subgroups.
Estimated
acute
exposures
are
5%
of
the
aPAD
or
less
for
all
population
subgroups
at
the
95th
percentile
of
exposure.

Occupational
Exposure
Inhalation
exposure
of
pesticide
handlers
is
likely
during
the
use
of
tau­
fluvalinate
in
a
variety
of
occupational
environments.
Since
no
chemical­
specific
handler
exposure
data
are
available
for
tau­
fluvalinate,
short­
and
intermediate­
term
inhalation
exposures
were
assessed
using
data
from
the
Pesticide
Handlers
Exposure
Database
(
PHED)
Version
1.1.
PHED
data
were
used
with
other
HED
standard
values
for
areas
treated
per
day,
body
weight
and
the
level
of
personal
protective
equipment
(
PPE)
and
engineering
controls
to
assess
handler
exposures
to
taufluvalinate
Using
these
assumptions,
the
calculated
occupational
handler
exposures
for
all
exposure
scenarios
at
all
levels
of
protection,
including
baseline
(
i.
e.,
no
respirator),
do
not
exceed
HED's
level
of
concern
(
i.
e.,
MOEs
>
100).
Estimated
inhalation
exposures
for
handlers
wearing
respirators,
as
required
by
current
labels,
are
well
below
HED's
level
of
concern
(
MOEs
>
900).
Post­
application
inhalation
exposure
of
workers
to
tau­
fluvalinate
is
expected
to
be
minimal,
except
in
greenhouses,
where
potential
inhalation
exposure
is
mitigated
by
the
ventilation
requirements
of
the
Worker
Protection
Standard.

Dermal
exposure
to
tau­
fluvalinate
is
expected
to
be
largely
self­
limiting
due
to
the
irritation
that
occurs
on
contact
with
the
pesticide
as
a
result
of
the
characteristic
"
pyrethroid
reaction".
Therefore,
dermal
handler
and
post­
application
exposures
were
not
assessed.
HED
believes
the
issue
of
dermal
exposure
can
be
best
addressed
by
labeling
to
avoid
contact
with
skin
and
instructions
to
wash
the
affected
area
immediately
following
contact.
Currently
approved
end­
use
product
labels
include
adequate
precautionary
labeling.

Conclusions
Tau­
fluvalinate
is
an
insecticide/
miticide
with
very
limited
annual
domestic
usage.
Under
the
conditions
of
its
current
use,
human
health
risks
to
workers
handling
the
pesticide
or
to
the
general
population,
including
infants
and
children,
are
well
below
HED's
level
of
concern.

2.0
Ingredient
Profile
Tau­
fluvalinate
is
an
insecticide/
miticide
in
the
pyrethroid
class
of
pesticides.
It
acts
as
an
axonic
poison
by
interfering
with
the
sodium
channels
of
both
the
peripheral
and
central
nervous
systems,
stimulating
repetitive
nervous
discharges,
leading
to
paralysis.
It
is
registered
for
a
single
food
Page
7
of
59
use
(
beehives/
honey)
and
several
non­
food
uses,
including
ornamentals
(
outdoor
and
containergrown
greenhouse,
interior
plantscapes,
dip
for
cuttings),
building
surfaces/
perimeters,
ant
mounds
and
certain
crops
(
carrots
and
Brassica/
cole
crops)
grown
for
seed.

Tau­
fluvalinate
products
are
registered
in
the
U.
S.
to
Wellmark
International.
Currently
registered
end­
use
formulations
include
Mavrik
Aquaflow
(
EPA
Reg.
No.
2724­
478),
a
flowable
formulation
containing
2
lbs.
tau­
fluvalinate
per
gallon,
and
Zoecon
RF­
318
Apistan
Strip
(
EPA
Reg.
No.
2724­
406),
an
impregnated
plastic
formulation
containing
10.25%
tau­
fluvalinate
by
weight.
Mavrik
is
registered
for
use
on
ornamentals
(
outdoor
and
container­
grown,
greenhouse,
interior
plantscapes,
dip
for
cuttings),
building
perimeters
and
ant
mounds;
as
well
as
on
carrots
and
Brassica/
cole
crops
grown
for
seed
under
FIFRA
§
24
(
c)
Special
Local
Need
registrations
in
California.
The
Apistan
Strip
is
registered
to
control
varroa
mites
in
beehives.

2.1
Summary
of
Registered/
Proposed
Uses
TABLE
2.1
Summary
of
Registered
Uses
of
Tau­
fluvalinate
Use
Site
Product
Maximum
Application
Rate
Application
Method
Maximum
No.
of
Applications
Greenhouses
(
nonfood
plants),
containerized
nursery
stock
Mavrik
Aquaflow
2724­
478
10.0
fl.
oz.
product
(
0.16
lb.
a.
i.)/
100
gal./
20,000
sq.
ft.
Broadcast,
fogger,
bench
4/
month
Interior
plantscapes
Mavrik
Aquaflow
2724­
478
10.0
fl.
oz.
product
(
0.16
lb.
a.
i.)/
100
gal.

0.5
fl.
oz./
5
gal./
1,000
sq.
ft.
Broadcast,
fogger,
bench
Not
Specified
(
NS)

Woody
and
herbaceous
ornamentals,
plantscapes
Mavrik
Aquaflow
2724­
478
10.0
fl.
oz.
product
(
0.16
lb.
a.
i.)/
100
gal./
20,000
sq.
ft.
Low­
pressure
fan
spray
(
on
base
of
stem
or
trunk)
24/
year
Flower
and
foliage
cuttings
Mavrik
Aquaflow
2724­
478
5.0
fl.
oz.
product
(
0.08
lb.
a.
i.)/
100
gal.
Dipping
NS
Eugenia
and
pepper
tree
Mavrik
Aquaflow
2724­
478
10.0
fl.
oz.
product
(
0.16
lb.
a.
i.)/
100
gal.
Spray
2
at
14­
day
intervals
Building
perimeters
(
outdoors)
Mavrik
Aquaflow
2724­
478
3
tsp.
product/
5
gal./
1,000
sq.
ft.
Low­
pressure
fan
spray
to
edge
of
structure
4/
month
Ant
Mound
Drench
Mavrik
Aquaflow
2724­
478
10.0
fl.
oz.
product
(
0.16
lb.
a.
i.)/
100
gal.;
1
gal./
mound
Drench
NS
TABLE
2.1
Summary
of
Registered
Uses
of
Tau­
fluvalinate
Use
Site
Product
Maximum
Application
Rate
Application
Method
Maximum
No.
of
Applications
Page
8
of
59
O
O
O
N
H
C
H
3
CH
3
CN
Cl
F
3
C
SLN
24(
c)
CA960010:
Carrots
grown
for
seed
Mavrik
Aquaflow
2724­
478
9.6
fl.
oz.
product
(
0.15
lb.
a.
i.)/
Acre
Aerial,
ground
NS
SLN
24(
c)
CA040022:
Brassica/
cole
crops
grown
for
seed
Mavrik
Aquaflow
2724­
478
9.6
fl.
oz.
product
(
0.15
lb.
a.
i.)/
Acre
Aerial,
ground
NS
Beehives
Zoecon
Apistan
Strip
RF­
318
2724­
406
1
strip
for
each
5
combs
of
bees
or
less
in
each
bee
chamber
Impregnated
strip:
Placed
in
empty
hives
with
gloved
hands.
Leave
strip
in
hive
for
6
to
8
weeks.
Treat
in
the
spring
and
fall.
5
strips/
year
2.2
Structure
and
Nomenclature
Tau­
fluvalinate
is
an
enriched
isomer
pesticide
resulting
from
the
partial
purification
of
racemic
fluvalinate.
Fluvalinate,
as
initially
synthesized,
was
a
mixture
of
diasterioisomers.
These
were
not
cis/
trans
isomers
as
is
the
case
with
some
pyrethroids.
The
chemical
structure
of
fluvalinate
contains
two
chiral
centers
with
two
optical
positions
possible
at
each.
Thus,
racemic
fluvalinate
is
a
mixture
of
four
optical
isomers,
designated
as
R­
2R,
R­
2S,
S­
2R
and
S­
2S.
Only
one
of
these
isomers
(
S­
2R),
however,
is
insecticidally
active.
In
1980,
process
changes
permitted
the
synthesis
of
fluvalinate
free
of
two
of
the
insecticidally
inactive
isomers,
resulting
in
a
compound
containing
only
two
of
the
optical
isomers
(
one
insecticidally
active
and
one
inactive)
and
twice
the
insecticidal
activity
of
racemic
fluvalinate.
This
enriched
isomer
form
was
termed
"
halfresolved
or
"(
 RS,
2R)­
fluvalinate".

TABLE
2.2.
Tau­
fluvalinate
Nomenclature
Chemical
Structure
Empirical
Formula
C26H22ClF3N2O3
Common
name
Tau­
fluvalinate
IUPAC
name
(
RS)­
 ­
cyano­
3­
phenoxybenzyl
N­(
2­
chloro­
 ,
 ,
 ­
trifluoro­
p­
tolyl)­
D­
valinate
CAS
name
cyano­(
3­
phenoxyphenyl)
methyl
N­[
2­
chloro­
4­(
trifluoromethyl)
phenyl]­
Dvalinate
CAS
Registry
Number
102851­
06­
9
(
tau­
fluvalinate)
69409­
94­
5
(
unresolved
fluvalinate)
TABLE
2.2.
Tau­
fluvalinate
Nomenclature
Page
9
of
59
Known
Impurities
of
Concern
None
Chemical
Class
Pyrethroid
End
Use
Products
(
EPs):

2724­
478
Flowable
formulation
containing
2
lbs.
tau­
fluvalinate
per
gallon
Mavrik
Aquaflow
2724­
406
Impregnated
plastic
formulation
containing
10.25%
tau­
fluvalinate
by
weight.
Zoecon
Apistan
Strip
RF­
318
2.3
Physical
and
Chemical
Properties
Tau­
fluvalinate
has
low
volatility
and
low
water
solubility.
Based
on
these
characteristics,
significant
human
exposure
via
the
inhalation
route
or
from
drinking
water
would
not
be
expected.

TABLE
2.3.
Physicochemical
Properties
Parameter
Value
Reference
Boiling
point
164

C
at
0.07
mm
Hg
D165590,
3/
4/
92,
F.
Toghrol
pH
Not
applicable;
tau­
fluvalinate
is
practically
insoluble
in
water
Density,
bulk
density,
or
specific
gravity
1.262
g/
mL
at
25

C
D165590,
3/
4/
92,
F.
Toghrol
Water
solubility
2.4
ppb
at
25

C
D272832
and
D273228,
3/
21/
01,
K.
Dockter
Solvent
solubility
at
25

C
55.31
g/
100
mL,
methanol
24.05
g/
100
mL,
octanol
Miscible
at
all
levels
in
isooctane,
toluene,
acetonitrile,
2­
propanol,
dimethylformamide,
and
1­
octanol
D272832
and
D273228,
3/
21/
01,
K.
Dockter
D165590,
3/
4/
92,
F.
Toghrol
Vapor
pressure
<
1.0
x
10­
5
Pa
(<
10­
7
torr),
25

C
D272832
and
D273228,
3/
21/
01,
K.
Dockter
Dissociation
constant,
pKa
Not
applicable
due
to
the
instability
of
tau­
fluvalinate
under
acidic
and
basic
conditions,
and
its
extremely
low
water
solubility.
Phase
4
Review,
1/
16/
91
Octanol/
water
partition
coefficient
POW
>
106,
25

C
D272832
and
D273228,
3/
21/
01,
K.
Dockter
UV/
visible
absorption
spectrum
Not
available
Page
10
of
59
3.0
Metabolism
Assessment
3.1
Comparative
Metabolic
Profile
Rat/
Mouse:
There
are
both
rat
and
mouse
metabolism
studies
that
demonstrate
that
taufluvalinate
is
absorbed
and
excreted.

In
the
mouse,
approximately
59%
and
30%
of
the
applied
radioactive
dose
is
excreted
into
the
feces
and
urine,
respectively,
after
4
days
with
most
excreted
within
24
hours.
An
anilino
metabolite
was
identified
in
the
urine
but
several
other
metabolites
were
not
further
characterized.

In
the
rat
metabolism
study,
approximately
75%
of
the
administered
dose
was
recovered
in
the
excreta
24
hours
after
dosing
following
a
1
mg/
kg
dose.
A
higher
dose
of
200
mg/
kg
resulted
in
only
about
45%
of
the
dose
being
excreted
in
24
hours.
At
the
high
dose
level,
the
fecal
route
appeared
to
be
the
dominant
route
of
elimination
with
only
about
20%
of
the
dose
being
recovered
in
the
urine.
The
parent
compound
(
85%)
and
an
anilino
acid
(
2%)
represented
the
major
composition
of
the
feces.
For
the
1
mg/
kg
dose
group,
30­
40%
of
the
administered
dose
was
recovered
in
the
urine
with
elimination
half
lives
of
12
hours
for
males
and
15
hours
for
females.
Several
urinary
metabolites
were
identified,
with
the
major
urinary
metabolites
being
3­
(
4'­
hydroxyphenoxy)
benzoic
acid
and
3­
phenoxybenzoic
acid
(
3­
PBA).
A
proposed
metabolic
pathway
reflects
the
hydrolysis
and
cleavage
of
the
cyano
group
at
the
ester
linkage,
oxidation
of
the
triflouromethyl
group
and
hydroxylation
of
the
phenoxy
ring.
Specifically,
tau­
fluvalinate
is
initially
biotransformed
to
3­
phenoxybenzyl
alcohol
which
is
then
oxidized
to
3­
phenoxybenzoic
acid
(
3­
PBA)
and
3­(
4'
hydroxyphenoxy)
benzoic
acid.
Tau­
fluvalinate
is
also
metabolized
to
anilino
acid
which
may
be
hydroxylated
and
converted
to
the
lactone
of
anilino
acid,
or
may
form
haloaniline
or
diacid
(
Memo
from
W.
B.
Greer,
8/
26/
93,
Fluvalinate
­
Submission
of
a
Rat
Metabolism
Study
in
Compliance
with
Reregistration
Requirements
with
attached
DER,
approved
8/
27/
93).

Plants:
The
existing
plant
metabolism
studies
indicate
that
tau­
fluvalinate
is
metabolized
to
decarboxy­
fluvalinate
(
minor
pathway)
or
is
cleaved
to
form
anilino
acid
and
phenoxybenzyl
alcohol
(
major
pathway),
both
of
which
are
conjugated
to
carbohydrates
before
incorporation
into
the
carbon
pool.
The
major
metabolite
found
in
plants
was
3­
PBA.
Other
metabolites
accounted
for
less
than
10%
of
the
TRR.

Ruminants:
In
metabolism
studies
in
ruminants
most
(~
80%)
of
the
TRR
was
found
in
the
GI
tract
(
50%),
urine
(
25%)
and
feces
(
4.2%),
with
minor
amounts
found
in
milk,
kidney,
liver,
muscle
and
fat.
Tau­
fluvalinate,
per
se,
comprised
81%
and
84%
of
the
TRR
in
the
GI
tract
and
in
feces.
The
major
metabolites
found
in
urine
were
3­
PBA
and
3­
PBA/
glycine
conjugate.
Minor
metabolites
found
in
ruminant
matrices
included
4'­
OH
fluvalinate
and
various
PBA
conjugates.

Summary:
The
available
metabolism
studies
indicate
that
tau­
fluvalinate
is
metabolized
in
a
similar
way
in
rodents,
plants
and
ruminants,
with
unmetabolized
parent
and
3­
PBA
(
or
its
conjugates)
comprising
the
majority
of
the
residue
in
most
matrices.
Page
11
of
59
3.2
Nature
of
the
Residue
in
Foods
The
registered
use
of
tau­
fluvalinate
in
beehives
does
not
involve
the
direct
application
of
taufluvalinate
to
honey,
but
rather
the
possible
transfer
of
secondary
residues
from
tracking
by
bees
who
have
been
in
contact
with
the
insecticide
strips
containing
the
pesticide.
A
beehive
metabolism
(
i.
e.,
nature
of
the
residue)
study
was
not
required
for
tau­
fluvalinate.
Generally,
HED
considers
all
available
metabolism
data
(
e.
g.,
plant,
livestock,
other
arthropods)
and
environmental
fate
data
(
e.
g.,
hydrolysis
studies)
in
determining
the
residue
of
concern
in
honey
from
pesticide
use
in
beehives
(
Residue
Data
Requirements
for
Uses
in
Beehives,
Chem
SAC
memo,
2/
25/
99).
Based
on
the
available
data
for
tau­
fluvalinate,
the
Team
has
determined
that
the
residue
of
concern
in
honey
is
tau­
fluvalinate,
per
se.
The
available
data
are
discussed
below.

3.2.1.
Description
of
Primary
Crop
Metabolism
Currently,
there
are
no
registered
uses
of
tau­
fluvalinate
on
plant
commodities.
Previously
registered
uses
on
cotton
and
coffee
have
been
cancelled
and
the
associated
tolerances,
including
tolerances
for
secondary
residues
in
animal
commodities,
have
been
revoked.
Metabolism
studies
on
several
crops
(
including
cotton,
corn,
tomatoes,
lettuce,
cabbage,
bean,
alfalfa
and
apples)
were
submitted
by
the
registrant
in
connection
with
previously
registered/
pending
food
uses.
The
studies
on
cotton,
corn,
tomatoes,
lettuce,
cabbage
and
bean
were
determined
to
be
unacceptable
for
various
reasons,
including
inadequate
radiolabeling
of
the
test
material
and/
or
the
need
to
further
elucidate
the
unknown
and
unextractable
portions
of
the
TRR
(
G.
Herndon
memo
of
2/
6/
92).
In
its
review
of
an
IR­
4
request
to
amend
the
tolerance
for
coffee,
HED
concluded
that
the
available
plant
metabolism
studies
with
alfalfa
and
apples
were
adequate
to
support
the
registered
use
of
tau­
fluvalinate
on
coffee
as
well
as
then
pending
import
tolerances
for
apples,
kiwi,
and
oriental
pears
(
G.
Herndon
memo
of
2/
13/
92
concerning
PP#
0F03847).
[
Note:
The
coffee
use
has
been
cancelled
and
the
import
tolerances
are
no
longer
being
pursued].
The
residue
of
concern
was
determined
to
be
fluvalinate,
per
se.
HED
noted
that
an
additional
plant
metabolism
study
would
be
required
to
support
the
registration
of
any
other
uses
of
fluvalinate
(
or
tau­
fluvalinate)
on
food/
feed
crops
The
available
plant
metabolism
studies
indicate
that
tau­
fluvalinate
is
metabolized
to
decarboxyfluvalinate
(
minor
pathway)
or
is
cleaved
to
form
anilino
acid
and
phenoxybenzyl
alcohol
(
major
pathway),
both
of
which
are
conjugated
to
carbohydrates
before
incorporation
into
the
carbon
pool.

3.2.2
Description
of
Livestock
Metabolism
There
are
currently
no
registered
uses
of
tau­
fluvalinate
on
any
livestock
feed
item.
Therefore,
data
pertaining
to
the
nature
of
the
residue
in
livestock
are
not
required.
However,
ruminant
and
poultry
metabolism
studies
for
tau­
fluvalinate
were
previously
submitted
by
the
registrant
in
support
of
the
cotton
use
which
has
since
been
cancelled.
Based
on
these
studies,
HED
concluded
that
the
qualitative
nature
of
the
residue
in
animals
was
adequately
understood
(
R.
Cook
memo
of
12/
10/
90
concerning
PP#
0F03347;
and
W.
Cutchin
memo
of
6/
16/
95
­
Response
to
Inquiry.
Current
Status
of
Fluvalinate.
DP
Barcode:
D209130).
The
residue
of
concern
in
livestock
commodities
was
determined
to
be
tau­
fluvalinate,
per
se.
Page
12
of
59
Tau­
fluvalinate
is
metabolized
in
ruminant
animals
the
following
way:
50
percent
in
the
gastrointestinal
tract
(
81%
tau­
fluvalinate);
25
percent
in
urine
(
metabolism
of
tau­
fluvalinate
to
3­
phenoxybenzoic
acid
(
3­
PBA)
followed
by
conjugation
of
3­
PBA
with
glycine);
4.2
percent
in
feces
(
84%
tau­
fluvalinate);
0.18
percent
in
milk
(
46%
3­
PBA
glycine,
33%
tau­
fluvalinate
and
6
to
10%
3­
PBA
glycine
bound
to
unextractable
residues);
0.20
percent
in
kidney
(
6%
taufluvalinate
34%
3­
PBA,
2%
PB
alcohol,
18%
3­
PBA
glycine,
13%
4'
OH­
3­
PBA
glycine
and
1.3%
3­
PBA
glucoside);
and
0.19
percent
in
liver
(
48%
tau­
fluvalinate,
3.7%
4'
OH
fluvalinate,
7.9%
3­
PB
Aldehyde,
7.8%
3­
PBA
glycine
and
0.7%
3­
PBA
glucoside).
Of
the
radiolabeled
residue
found
in
fat,
39
percent
was
identified
as
tau­
fluvalinate,
15%
3­
PB
Aldehyde;
in
muscle
40
percent
was
tau­
fluvalinate,
4%
4'­
OH
fluvalinate
and
12%
3­
PB
aldehyde.

3.2.3
Description
of
Rotational
Crop
Metabolism,
including
identification
of
major
metabolites
and
specific
routes
of
biotransformation
Tau­
fluvalinate
is
presently
not
registered
for
use
on
any
annual
crop;
therefore,
no
residue
chemistry
data
are
required
under
these
guideline
topics.

3.3
Environmental
Degradation
Tau­
fluvalinate
is
highly
immobile
(
K
d
values
between
853
and
1,708
with
corresponding
K
oc
values
between
110,000
and
370,000,
respectively)
and
practically
insoluble
in
water
(
2.4
ppb
at
25C),
indicating
a
low
potential
for
significant
residues
in
drinking
water.
Nevertheless,
taufluvalinate
is
registered
for
outdoor,
non­
food
uses
(
including
carrots
and
Brassica/
cole
crops
grown
for
seed,
ornamentals
and
building
perimeters)
that
could
potentially
result
in
residues
in
surface
or
ground
water.

The
major
routes
of
degradation
of
tau­
fluvalinate
in
laboratory
studies
are
by
abiotic
processes
(
photodegradation
in
water
and
soil,
and
pH
dependent
hydrolysis)
and
biotic
processes
under
aerobic
conditions.
Tau­
fluvalinate
is
expected
to
be
rapidly
degraded
in
both
soil
and
aquatic
environments
under
aerobic
conditions
but
is
expected
to
be
stable
under
anaerobic
conditions.
Tau­
fluvalinate
degraded
rapidly
by
aqueous
photolysis
with
a
half
life
of
1
day
but
was
slightly
more
stable
to
soil
photolysis
with
a
half
life
of
18
days.
Tau­
fluvalinate
degraded
in
an
aerobic
soil
metabolism
study
with
half
lives
of
8
and
15
days
and
had
a
half
life
of
63
days
in
a
supplemental
terrestrial
field
dissipation
study.
In
an
anaerobic
aquatic
metabolism
study
taufluvalinate
degraded
with
half
lives
of
255
and
413
days
in
the
whole
system.

In
water,
the
major
degradates
of
tau­
fluvalinate
seen
in
environmental
studies
were
3­
Phenoxybenzaldehyde
(
3­
PB
Aldehyde),
2­(
2­
Chloro­
4­
carboxyl)
anilino­
3­
methylbutanoic
acid,
2­[
4­
Carboxyl­
2­(
chloro)
anilino]­
3­
methylbutanoic
acid
(
Diacid),
2­(
2­
Chloro­
4­
trifluoromethyl)­
anilino­
3­
methylbutanoic
acid,
2­[
2­
Chloro­
4­(
trifluoromethyl)­
anilino]­
3­
methylbutanoic
acid
(
Anilino
acid),
2­
Chloro­
4­
trifluoromethylaniline
(
Haloaniline),
and
Cyanohydrin.
In
addition,
4­
amino­
3­
chlorobenzoic
acid
and
carbon
dioxide
were
found
as
minor
degradates
in
various
studies.

3.4
Toxicity
Profile
of
Major
Metabolites
and
Degradates
Page
13
of
59
Toxicology
data
for
the
major
metabolite
of
tau­
fluvalinate,
3­
PBA,
indicate
that
this
compound
and
its
conjugates
are
not
of
toxicological
concern.
Specific
data
are
not
available
for
other
metabolites;
however,
the
major
plant
and
animal
metabolites
are
also
metabolites
in
the
rat,
and,
therefore,
their
toxicity
was
assessed
when
the
parent
was
studied.
In
addition,
none
of
the
major
plant
or
animal
metabolites
contains
the
intact
ester
linkage
responsible
for
the
neurotoxicity
of
tau­
fluvalinate.

3.5
Summary
of
Residues
for
Tolerance
Expression
and
Risk
Assessment
3.5.1
Tabular
Summary
Table
3.5.
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
Plants
Honey
Parent
Tau­
Fluvalinate
Parent
Tau­
Fluvalinate
Rotational
Crop
N/
A
Livestock
Ruminant
Poultry
Drinking
Water
Parent
Tau­
Fluvalinate
Not
Applicable
3.5.2
Rationale
for
Inclusion
of
Metabolites
and
Degradates
The
risk
assessment
team
concluded
that
the
residue
of
concern
for
risk
assessment
purposes
in
all
commodities
and
drinking
water
consists
of
parent
tau­
fluvalinate
only.
The
team
based
its
decision
on
the
following
evidence:
(
1)
The
major
metabolite
in
plants
and
animals,
3­
phenoxybenzoic
acid
(
3­
PBA),
and
its
conjugates
are
not
of
concern
based
on
toxicology
data
for
PBA;
(
2)
the
major
plant
and
animal
metabolites
are
also
metabolites
in
the
rat,
and,
therefore,
their
toxicity
was
assessed
when
the
parent
was
studied;
and
(
3)
none
of
the
major
plant
or
animal
metabolites
contains
the
intact
ester
linkage
responsible
for
the
neurotoxicity
of
tau­
fluvalinate.

The
team's
decision
is
consistent
with
HED's
earlier
determination
regarding
the
toxicological
significance
of
tau­
fluvalinate
metabolites
(
PP#
6G3401/
FAP#
6H5501
­
Fluvalinate
on
Various
Fruits
and
Vegetable
Crops
­
Response
to
Residue
Chemistry
Branch's
Memorandum
Dated
August
21,
1986
Concerning
the
Toxicological
Significance
of
Various
Animal
and
Plant
Metabolites;
W.
Greear;
3/
7/
87).
In
the
1987
memo,
HED
concluded
that
none
of
the
major
plant
or
animal
metabolites
of
tau­
fluvalinate
were
of
toxicological
concern.

4.0
Hazard
Characterization/
Assessment
4.1
Hazard
Characterization
Page
14
of
59
Tau­
fluvalinate
is
a
pyrethroid
insecticide
of
the
type
II
class.
Tau­
fluvalinate
is
moderately
acutely
toxic,
being
classified
in
Toxicity
Category
II
for
oral
toxicity
and
Category
III
for
dermal
toxicity.
Tau­
fluvalinate
is
not
a
primary
irritant
to
either
the
eye
(
Toxicity
Category
III)
or
skin
(
Toxicity
Category
IV)
and
is
not
a
dermal
sensitization
agent.

As
a
type
II
pyrethroid,
tau­
fluvalinate
causes
the
"
pyrethroid
reaction",
a
specific
type
of
dermal
irritation
following
contact.
The
"
pyrethroid
reaction"
is
unlike
the
primary
dermal
irritation
assessed
in
acute
or
subchronic
dermal
irritation
studies.
The
"
pyrethroid
reaction"
occurs
during
feeding
studies
when
dermal
contact
is
made
with
the
feed.
The
rats
or
mice
develop
skin
lesions
that
can
potentially
become
infected
to
such
a
degree
that
the
animals
need
to
be
sacrificed
for
humane
reasons.
The
"
pyrethroid
reaction"
can
limit
the
dose
levels
and
duration
of
exposure
to
confound
subchronic
and
particularly
chronic
exposure
studies
when
dosing
is
by
incorporation
of
the
test
material
into
the
feed.
A
study
in
rats
was
conducted
to
establish
that
the
dermal
reactions
do
not
come
when
tau­
fluvalinate
is
dosed
by
gavage
and
result
from
dermal
contact
with
either
the
feed
or
the
feces
or
emesis
(
for
dogs).
Thus,
more
definitive
subchronic
and
chronic
studies
were
done
by
gavage.

Subchronic
and
chronic
oral
systemic
toxicity.
In
dogs,
systemic
responses
to
treatment
by
gavage
were
limited
to
body
weight
decreases
and
liver
weight
increases
as
well
as
emesis
and
salivation.
In
the
rat
subchronic
study,
body
weight
and
liver
weight
were
established
as
systemic
effects
of
treatment.
In
the
chronic
rat
study,
body
weight
decrease
was
the
main
response
to
treatment.
In
the
mouse
carcinogenicity
study,
no
effects
on
body
weight
were
noted,
but
the
LOAEL
was
based
on
chronic
nephritis.
Clinical
signs
of
pyrethroid
toxicity
were
noted
in
the
subchronic
and
chronic
studies.

Subchronic
dermal
toxicity.
A
21­
day
dermal
toxicity
study
in
rabbits
demonstrated
skin
lesions
at
100
to1000
mg/
kg/
day
that
may
be
related
to
secondary
effects
of
the
"
pyrethroid
reaction".
In
addition,
there
were
systemic
effects
at
500
mg/
kg/
day
and
above,
including
decreased
food
consumption
and
body
weight
effects.

Subchronic
inhalation
toxicity.
There
is
no
study
that
assesses
subchronic
inhalation
toxicity.
Tau­
fluvalinate
may
have
a
special
problem
with
regard
to
the
unknown
consequences
resulting
from
the
property
of
this
chemical
to
cause
the
"
pyrethroid
reaction"
once
the
respiratory
tract
is
exposed
to
the
chemical.
In
particular,
persons
with
asthma
and
emphysema
may
be
especially
sensitive.
Prevention
of
possible
respiratory
hazard
associated
with
the
"
pyrethroid
reaction"
should
be
accomplished
by
requiring
the
use
of
respirators
for
those
product
uses
where
spray
mists
or
other
potentially
respirable
atmospheres
containing
tau­
fluvalinate
occur.

Developmental
and
reproductive
toxicity.
The
rat
developmental
toxicity
study
did
not
demonstrate
developmental
toxicity
at
the
highest
dose
tested.
The
rabbit
developmental
toxicity
demonstrated
some
signs
of
skeletal
variations
(
curved
tibia
and
fibula)
but
at
the
same
dose
where
there
was
maternal
toxicity.
There
were
no
effects
of
tau­
fluvalinate
on
reproductive
performance.
The
offspring
were
noted
to
have
tremors
in
one
generation
and
to
have
slight
body
weight
decrease
in
another
generation,
but
these
effects
occurred
at
a
dose
that
was
also
toxic
to
the
parents.
Page
15
of
59
Neurotoxicity.
Tau­
fluvalinate
is
a
pyrethroid
insecticide
that
acts
on
the
Na
conductance
channel
in
both
peripheral
and
central
nervous
systems.
The
"
pyrethroid
reaction"
may
be
considered
to
be
one
manifestation
of
the
ability
of
this
chemical
to
act
on
nerve
endings
and
cause
its
characteristic
tingling
sensations.
The
non­
guideline
"
acute"
neurotoxicity
study
with
7
daily
doses
in
males
only
resulted
in
several
clinical
signs
related
to
nerve
stimulation,
and
there
was
evidence
of
nerve
fiber
degeneration.
The
subchronic
neurotoxicity
study
did
not
reveal
nerve
fiber
degeneration
but
demonstrated
excessive
grooming
and
bulging
eyes,
signs
of
either
nerve
stimulation
or
agitation.

Carcinogenicity.
Tau­
fluvalinate
is
not
considered
a
likely
human
carcinogen
since
neither
the
rat
nor
the
mouse
carcinogenicity
studies
were
determined
to
demonstrate
a
positive
response
for
increased
tumors.

Mutagenicity.
There
is
no
mutagenicity
concern.
Tau­
fluvalinate
was
not
shown
to
be
mutagenic
or
to
have
genetic
toxicity
in
several
studies
including
the
Salmonella
strains
(
Ames
test),
sister
chromatid
exchange,
chromosome
aberrations
in
rats
and
unscheduled
DNA
synthesis.

Metabolism.
There
are
both
rat
and
mouse
metabolism
studies
that
demonstrate
that
taufluvalinate
is
absorbed
and
excreted.
In
the
mouse,
approximately
59%
and
30%
of
the
applied
radioactive
dose
is
excreted
into
the
feces
and
urine,
respectively,
after
4
days,
with
most
excreted
within
24
hours.
An
anilino
metabolite
was
identified
in
the
urine
but
several
other
metabolites
were
not
further
characterized.
In
the
rat,
approximately
75%
of
the
administered
dose
was
recovered
in
the
excreta
24
hours
after
dosing
at
a
1
mg/
kg
dose.
A
higher
dose
of
200
mg/
kg
resulted
in
only
about
45%
of
the
dose
being
excreted
in
24
hours.
At
the
high
dose
level,
the
fecal
route
appeared
to
be
the
dominant
route
of
elimination
with
only
about
20%
of
the
dose
being
recovered
in
the
urine.
The
parent
compound
(
85%)
and
an
anilino
acid
(
2%)
represented
the
major
composition
of
the
feces.
For
the
1
mg/
kg
dose
group,
30­
40%
of
the
administered
dose
was
recovered
in
the
urine
with
elimination
half
lives
of
12
hours
for
males
and
15
hours
for
females.
Several
urinary
metabolites
were
identified,
with
the
major
urinary
metabolites
being
3­
(
4'­
hydroxyphenoxy)
benzoic
acid
and
3­
phenoxybenzoic
acid.

Dermal
absorption.
There
is
no
acceptable
guideline
study
that
demonstrates
a
dermal
absorption
factor.
There
is
one
study
(
Accession
No.:
250142,
classified
as
unacceptable/
guideline,
not
ungradable)
that
demonstrated
that
only
4%
of
the
applied
dose
was
absorbed
in
a
single
male
rat.
Comparison
of
the
LOAEL
of
125
mg/
kg/
day
(
based
on
"
anorexia
and
general
depression")
from
the
rabbit
developmental
toxicity
study
with
the
LOAEL
of
500
mg/
kg/
day
(
based
on
systemic
response
of
decreased
food
consumption)
from
the
21­
day
dermal
toxicity
study
would
suggest
that
a
dermal
absorption
factor
of
25%
(
125
mg/
kg/
day
÷
500
mg/
kg/
day
x
100)
would
be
appropriate.

Endocrine
disruption.
There
were
no
indications
based
on
the
animal
studies
submitted
for
registration
purposes
that
indicate
that
tau­
fluvalinate
affects
either
the
estrogen,
androgen
or
thyroid
or
other
hormone
systems.
Page
16
of
59
Table
4.1a
Acute
Toxicity
Profile
­
Tau­
fluvalinate
Guideline
No.
Study
Type
MRID(
s)
(
Year)
Results
Toxicity
Category
870.1100
Acute
oral
­
rat
0094103
LD50
=
282
(
218­
365)
mg/
kg
­
males
261
(
194­
353)
mg/
kg
­
females.
II
870.1200
Acute
dermal
­
rabbit
41597301
(
1998)
LD50
>
2000
mg/
kg
III
870.1300
Acute
inhalation
­
rat
­­
Not
applicable
(
1).­­

870.2400
Acute
eye
irritation
­
rabbit
00144622
(
1984)
Slight
conjunctival
discharge
observed
one
hour
post
instillation.
Conjunctival
swelling
and
redness
noted
for
up
to
three
days.
III
870.2500
Acute
dermal
irritation
­
rabbit
00144623
(
1984)
PII
=
0.8
IV
870.2600
Skin
sensitization
­
guinea
pig
41889714
(
1990)
Not
a
sensitizer.
Not
applicable
(
1)
­
The
vapor
pressure
of
technical
tau­
fluvalinate
is
<
1
x
10
­
7
torr
at
25

C
(
i.
e.
is
a
viscous
liquid).
Refer
to
B.
Greear
memo
dated
01/
10/
91.

Table
4.1b
Subchronic,
Chronic
and
Other
Toxicity
Profile
­
Tau­
fluvalinate
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
870.3100
90­
Day
oral
toxicity
­
rat.
International
Research
and
Development,
Study
#
322­
047,
9/
24/
81
00094109
(
1981)
92069032
(
1990)
Acceptable/
Guideline
0,
0.3,
1,
3,
30
or
50
mg/
kg/
day.
(
Technical
­
"
half
resolved")
Systemic:
NOAEL
=
3
mg/
kg/
day
LOAEL
=
30
mg/
kg/
day
based
on
enlarged
lymph
nodes,
deceased
Hb,
Hct
and
RBC
counts
and
increased
organ
and
ratio
weights.
Dermal
("
pyrethroid
reaction"):
NOAEL
=
1
mg/
kg/
day
LOAEL
=
3
mg/
kg/
day
based
on
skin
lesions.

870.3100
(
b)
90­
day
oral
toxicity
­
mouse.
Litton
Bionetics,
Inc.,
Study
No.:
22088,
11/
1/
81
00094113
(
1981)
Supplementary
0,
1,
3,
30,
50
or
100
mg/
kg/
day.
(
Technical
"
half
resolved").
NOAEL
­
could
not
be
established
due
to
the
"
pyrethroid
reaction"
­
skin
lesions,
with
their
sequella
(
increased
WBC
counts,
enlarged
lymph
nodes,
infected
eyes,
and
splenic
changes)
in
all
dosed
groups.
At
higher
doses
decreased
body
weight
and
other
blood
effects
and
ovary
weight
and
ovary
cysts.
Table
4.1b
Subchronic,
Chronic
and
Other
Toxicity
Profile
­
Tau­
fluvalinate
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
Page
17
of
59
870.3200
21/
28­
Day
dermal
toxicity
­
rabbit
Elars
BioResearch
Lab,
Inc,
Study
No.:
1675­
P,
October
10,
1981.
00094115
(
1981)
92069034
(
1990)
Acceptable/
Guideline
Systemic:
NOAEL
=
100
mg/
kg/
day
LOAEL
=
500
mg/
kg/
day
based
on
decreased
food
consumption.
Dermal:
(
site
of
application)
Minimal
effects
at
100
mg/
kg/
day.
Indications
of
"
pyrethroid
reaction
at
higher
doses
(
biting
and
scarring).

Non­
Guideline
90­
Day
dermal
toxicity
­
rat.
IRDC,
Study
No.:
322049­
322058,
Jan
1,
1982.
00126175
(
1982).
249604
(
1982)
"
Minimum"
(
Non­
Guideline)
Study
summary
does
not
give
a
NOAEL
or
LOAEL
but
discusses
mechanism
of
skin
lesion
development.
States
that
the
dermal
exposure,
and
not
oral
exposure,
results
in
"
pyrethroid
reaction".
Study
is
not
appropriate
for
dermal
exposure
endpoint.

870.3465
90­
Day
inhalation
toxicity
No
study
available.

870.3700a
Prenatal
developmental
­
rats
Argus
Research
Labs,
Study
No.:
1819­
011,
2/
6/
98.
44743301
(
1998)
Acceptable/
Guideline.
0,
5,
10
or
15
mg/
kg/
day.
Maternal
NOAEL
=
5
mg/
kg/
day
LOAEL
=
10
mg/
kg/
day
based
on
decreased
body
weight
and
food
consumption.
Developmental
NOAEL
=

15
mg/
kg/
day.
No
effects
seen
at
highest
dose
tested.

870.3700b
Prenatal
developmental
­
rabbits
Hazleton
Laboratories,
Study
No.:
777­
137,
12/
23/
81
0094112
(
1981)
92069038
(
1990)
Acceptable/
Guideline
0,
5,
25
or
125
mg/
kg/
day.
Maternal
NOAEL
=
25
mg/
kg/
day
LOAEL
=
125
mg/
kg/
day
based
on
anorexia
and
general
depression.
Developmental
NOAEL
=
25
mg/
kg/
day
LOAEL
=
125
mg/
kg/
day
based
on
skeletal
anomalies,
curved
tibia
and
fibula.

870.3800
Reproduction
and
fertility
effects
­
rats
Huntingdon
Research
Center,
Study
No.;
MCI
56/
8694,
7/
2/
86.
44596601
(
1986)
Acceptable/
Guideline
0/
0,
0.76/
0.84,
1.90/
2.08
or
9.53/
10.51
mg/
kg/
day
for
males/
females.
Parental/
Systemic
NOAEL
=
1.90/
2.08
mg/
kg/
day
LOAEL
=
9.53/
10.51
mg/
kg/
day
based
on
clinical
signs
(
skin
ulcerations.).
Reproductive:
LOAEL
>
9.53/
kg/
day
Offspring:
NOAEL
=
1.90/
2.08
mg/
kg/
day
LOAEL
=
9.53/
10.51
mg/
kg/
day
based
on
tremors
during
lactation
in
both
litters,
decrease
in
pup
weight
in
F2
generation
(
12%,
p
<
0.05)
and
slightly
lower
litter
size.

870.4100a
Chronic
toxicity
­
rat
Refer
to
870.4300
combined
chronic
feeding/
carcinogenicity
study.
Table
4.1b
Subchronic,
Chronic
and
Other
Toxicity
Profile
­
Tau­
fluvalinate
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
Page
18
of
59
870.4100b
Chronic
toxicity
(
dog)
Covance
Laboratory,
Study
No.:
6398­
117,
12/
17/
98.
44743201
(
1998)
Acceptable/
Guideline
0,
3,
12
and
50
mg/
kg/
day.
NOAEL
=
3
mg/
kg/
day
LOAEL
=
12
mg/
kg/
day
based
on
decreased
body
weight
and
body
weight
gain
and
increased
liver
weight
in
females.

870.4200.
Carcinogenicity
­
mouse.
International
Research
and
Development,
Study
No.:
322­
048,
1/
12/
84.
00094889
(
1981)
00128336
(
1983)
00144628
(
1984)
92069036
(
1990)
Acceptable/
Guideline
for
carcinogenicity,
Supplementary
(
Acceptable/
Non­
Guideline)
for
chronic
feeding.
0,
2,
10
or
20
mg/
kg/
day.
Dermal:
NOAEL
=
2
mg/
kg/
day
LOAEL
=
10
mg/
kg/
day
based
on
dermal
lesions.
Systemic:
NOAEL
=
10
mg/
kg/
day
LOAEL
=
20
mg/
kg/
day
based
on
chronic
nephritis.

No
evidence
of
carcinogenicity.

870.4300.
Combined
chronic
feeding/
carcinogenicity
­
rats.
International
Research
and
Development,
Study
No.:
322­
053,
8/
27/
84.
00128334
(
1983)
00128335
(
1982)

92069048
(
1990)
Acceptable/
Guideline
0,
0.25,
0.5
1,
2.5,
10
and
20
(
10
and
20
for
17
weeks
only)
mg/
kg/
day.
NOAEL
=
0.5
mg/
kg/
day
LOAEL
=
1.0
mg/
kg/
day
based
on
clinical
signs
of
neurotoxicity
(
abnormal
stance,
ruffling
and
transient
hyperactivity,
followed
by
hypoactivity
in
males
and
females)
(
see
section
4.4)

No
evidence
of
carcinogenicity.

Gene
Mutation
870.5100.
Reverse
mutation
in
salmonella
T.
Litton
Bionetics,
Study
No.:
20988,
October
20,
1980.
00094116
(
1980)
Acceptable.
1
to
10,000

g/
plate..
With
or
without
metabolic
activation.
(
Fluvalinate)
No
evidence
of
mutagenic
response.

Cytogenetics
870.5375.
Sister
chromatid
exchange
in
CHO
cells.
Microbiological
Associates,
Study
No.:
T2258.334001,
March
1,
1984.
00144626
(
1984)
Acceptable.
250
to
2000
nL/
mL
(
Half­
resolved)
No
evidence
of
doubling
of
sister
chromatid
exchanges
or
changes
in
the
sister
chromatid
frequency
in
presence
or
absence
of
metabolic
activation.
Table
4.1b
Subchronic,
Chronic
and
Other
Toxicity
Profile
­
Tau­
fluvalinate
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
Page
19
of
59
Cytogenetics.
870.
5300.
Mouse
lymphoma
mutagenic
assay.
Microbiological
Associates,
Study
No.:
2258.701,
March
2,
1984.
00144625
(
1984)
Acceptable.
0.013
to
1

L/
mL
without
activation
and
0.0027
to
0.2

l/
mL
with
metabolic
activation.
(
Half­
resolved)
No
evidence
of
mutagenic
activity
in
presence
or
absence
of
metabolic
activation.

870.5300.
Mammalian
cells
in
culture
transformation
assay
in
mouse
fibroblast.
Litton
Bionetics.
Study
No.:
20992,
11/
18/
80.
00094117
(
1980)
00094118
(
1980)
Acceptable/
Nonguideline
No
evidence
of
transformation
with
or
without
metabolic
activation.

Other
Effects
870.
5550.
Unscheduled
DNA
synthesis
in
rat
hepatocytes.
Microbiological
Associates.
Study
No.:
T2258.380,
March
2,
1984.
00145614
(
1984)
Acceptable
0,
5,
10,
50
100
or
500
nl/
mL.
(
Half­
resolved).
No
indication
of
induction
of
unscheduled
DNA
repair.

870.6200a
Acute
neurotoxicity
screening
battery
43433901
(
1994)
Acceptable/
Non­
Guideline.*
0,
10
,
60
or
100
mg/
kg
*
Upgraded
in
RED
development
Study
does
not
follow
870.6200
guidelines:
Females
not
included,
motor
activity
not
assessed
and
used
multiple
(
7
day)
dosing.

NOAEL
=
10
mg/
kg/
day
LOAEL
=
60
mg/
kg/
day
based
on
body
weight
decreases,
clinical
signs
of
neurotoxicity
and
sciatic
nerve
pathology.

870.6200b
Subchronic
neurotoxicity
screening
battery
­
rat
Ricera,
Inc.
Study
No.:
2504,
6/
23/
99.
44900601
(
1999)
Acceptable/
Guideline*
0,
2,
8
or
32
mg/
kg/
day.

*
Upgraded
in
RED
development
NOAEL
=
Not
established.
LOAEL
<
2
mg/
kg/
day
based
on
clinical
signs
including
excessive
grooming
in
both
sexes
and
bulging
eyes
in
females.

*
A
study
does
not
have
to
demonstrate
a
NOAEL
to
be
classified
as
Acceptable/
Guideline.

870.6300
Developmental
neurotoxicity
No
study
available.
Table
4.1b
Subchronic,
Chronic
and
Other
Toxicity
Profile
­
Tau­
fluvalinate
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
Page
20
of
59
870.7485
Metabolism
and
pharmacokineticsrat
Sandoz
Agro,
Inc.
Study
No.:
480605,
Report
No.:
13,
5/
20/
1992.

870.7485,
Metabolism
­
mice.
Zoecon
Corp.
Study
No.:
3760­
2­
02­
84,
February
21,
1984.
43214101
(
1993)
42322301
(
1992)
­
rat
study
Acceptable/
Guideline.

072918
(
1984)
­
mouse
study
Acceptable/
Non­
Guideline.
There
are
both
rat
and
mouse
metabolism
studies
that
demonstrate
that
tau­
fluvalinate
is
absorbed
and
excreted.
In
the
mouse,
approximately
59%
and
30%
of
the
applied
radioactive
dose
is
excreted
into
the
urine
and
feces,
respectively,
after
4
days,
with
most
excreted
within
24
hours.
An
anilino
metabolite
was
identified
in
the
urine
but
several
other
metabolites
were
not
further
characterized.
In
the
rat,
approximately
75%
of
the
administered
dose
was
recovered
in
the
excreta
24
hours
after
dosing
at
1
mg/
kg
body
weight.
A
higher
dose
of
200
mg/
kg
resulted
in
only
about
45%
of
the
dose
being
excreted
in
24
hours.
At
the
high
dose
level,
the
fecal
route
appeared
to
be
the
dominant
route
of
elimination
with
only
about
20%
of
the
dose
being
recovered
in
the
urine.
The
parent
compound
(
85%)
and
an
anilino
acid
(
2%)
represented
the
major
composition
of
the
feces.
For
the
1
mg/
kg
dose
group,
30­
40%
of
the
administered
dose
was
recovered
in
the
urine
with
elimination
half
lives
of
12
hours
for
males
and
15
hours
for
females.
Several
urinary
metabolites
were
identified,
with
the
major
urinary
metabolites
being
3­(
4'­
hydroxyphenoxy)
benzoic
acid
and
3­
phenoxybenzoic
acid.

870.7600
Dermal
penetration
(
rat)
MRID
No.:
00126180
Unacceptable/
Guideline
Single
dose
Approximately
4%
of
the
dose
applied
to
a
single
male
rat
was
demonstrated
to
be
absorbed
with
the
resulting
radioactivity
being
found
in
the
feces
as
metabolites.

Special
studies
Special
90
day
dermal
study
to
investigate
mechanism
of
dermal
lesions
(
see
above
under
MRID
No.
00126175).

4.2
FQPA
Hazard
Considerations
4.2.1
Adequacy
of
the
Toxicity
Data
Base
The
toxicology
database
is
adequate
for
the
evaluation
of
risks
to
infants
and
children.
Relevant
studies
include
rat
and
rabbit
developmental
toxicity
studies,
a
rat
multi­
generation
reproduction
study
and
chronic/
carcinogenicity
feeding
studies
in
mice
and
rats.
In
addition,
acceptable
shortterm
(
non­
guideline)
and
subchronic
(
guideline)
neurotoxicity
studies
are
adequate
to
evaluate
the
neurotoxicity
of
tau­
fluvalinate.
There
is
no
developmental
neurotoxicity
study
available
in
the
database.

4.2.2
Evidence
of
Neurotoxicity
Tau­
fluvalinate
is
a
pyrethroid
insecticide
that
acts
on
the
nervous
system
in
insects.
The
mammalian
studies
demonstrate
typical
clinical
signs
associated
with
pyrethroid
neurotoxicity.
Some
evidence
of
nerve
degeneration
was
seen
at
higher
doses
in
the
acute
neurotoxicity
study.
Page
21
of
59
Acute
Neurotoxicity
Study.

In
a
non­
guideline
special
"
acute"
neurotoxicity
study
(
1994,
MRID
No.:
43433901),
10
male
Wistar
rats/
dose
group
received
7
daily
gavage
doses
of
0,
10
or
100
mg/
kg
of
tau­
fluvalinate
(
87.1%
a.
i.)
in
corn
oil
(
10
mL/
kg).
Due
to
severe
toxicity,
the
high
dose
was
discontinued
and
two
additional
groups
of
10
male
rats
received
7
daily
doses
if
0
or
60
mg/
kg.
Functional
observational
battery
tests
(
FOB)
were
conducted
with
clinical
examinations
pretreatment,
on
treatment
days
1,
2,
4
and
7
and
recovery
days
7
and
14.
Neural
tissues
were
examined
microscopically
from
5
control
and
5
rats
treated
with
60
mg/
kg
after
7
days
of
treatment
and
from
the
remaining
control
and
60
mg/
kg
animals
after
14
days
of
treatment.
Motor
activity
was
not
quantitated.

At
10
mg/
kg,
a
single
incidence
of
ruffled
fur
(
days
2
and
3),
salivation
(
day
2)
and
hyperalgesia
(
4/
10
vs
6/
20
controls)
were
noted.
Food
consumption
was
83%
of
control
on
days
1
to
4
of
treatment.
At
60
mg/
kg,
significantly
decreased
food
consumption
was
noted
during
dosing
and
recovery
(
86%,
77%,
74%,
84%,
and
90%
of
controls
on
days
4
and
7
and
on
recovery
days
1,
8
and
14,
respectively).
The
food
consumption
was
31%
and
26%
of
controls
on
days
1­
4
and
4­
7,
respectively.
Clinical/
behavioral
effects
seen
as
early
as
day
1
in
all
animals
treated
with
60
mg/
kg
but
not
in
controls
included
salivation,
ruffled
fur,
dyspnea,
muscle
spasms
and
sedation.
Other
observations
(
observed
in
30
to
90%
of
the
animals)
included
ataxia,
coarse
exertions
tremor,
hunched
posture,
gait
abnormalities,
serous
reddish
secretion
from
the
nose,
lids
half
closed,
miosis,
startle
response
hyperreaction,
reduced
grip
strength,
(
maximum
42.2%
compared
to
controls)
and
reduced
rearing
count.
Also
observed
were
fear,
diarrhea,
vibrissa
reflex
hyperreaction
and
hyperalgesia.
The
clinical/
behavioral
signs
were
transient
and
were
not
seen
at
the
end
of
recovery
period.
Peripheral
nerve
fiber
degeneration
was
observed
in
animals
treated
with
60
mg/
kg.
The
highest
incidence
and
severity
in
nerve
degeneration
was
seen
in
the
sciatic
nerve
(
minimal
to
moderate
lesions
in
4
animals
with
minimal
lesions
in
2
controls).
Following
recovery,
the
incidence
and
severity
of
the
lesions
was
decreased.
The
neurotoxicity
LOAEL
is
60
mg/
kg,
based
on
clinical
signs
of
toxicity
(
observed
as
early
as
day
1)
and
peripheral
nerve
degeneration
in
male
rats.
The
neurotoxicity
NOAEL
is
10
mg/
kg.
Note:
The
slight
decrease
in
food
consumption
and
incidence
of
ruffled
fur
and
salivation
were
not
included
in
the
NOAEL.
It
is
unlikely
that
these
occurred
following
a
single
dose.

This
study
is
classified
as
ACCEPTABLE/
Non­
Guideline
but
does
not
satisfy
the
requirement
for
a
series
870­
6200
acute
neurotoxicity
study
in
the
rat.
This
study
is
being
reclassified
from
the
original
classification
as
SUPPLEMENTARY.
The
study
is
not
eligible
to
be
upgraded
to
an
acceptable/
guideline
870­
6200
study
because
females
were
not
included,
no
motor
activity
assessments
were
made
and
the
study
included
multiple
daily
dosing
for
7
daily
doses.

Subchronic
Neurotoxicity
Study.

In
a
subchronic
oral
neurotoxicity
study
(
1999,
MRID
44900601),
groups
of
Wistar
rats
(
10
rats/
sex/
group)
were
administered
0,
2,
8,
or
32
mg/
kg/
day
of
Tau­
Fluvalinate
(
Lot
No.
56613870;
Batch
No.
96026;
88.3%
active
ingredient)
by
gavage
for
90
days.
An
additional
5
rats/
sex
in
the
control
and
high­
dose
groups
were
maintained
without
treatment
for
a
28­
day
recovery
period.
Functional
observational
battery
(
FOB)
and
motor
activity
(
MA)
testing
were
Page
22
of
59
performed
prior
to
administration,
during
weeks
1,
4,
8,
and
13,
and
after
the
recovery
period.
Body
weights
and
food
consumption
were
recorded
weekly
for
each
animal.
Neuropathologic
examinations
were
performed
on
6
animals
from
each
of
the
control
and
high­
dose
groups;
brain
weights
were
not
obtained.

In
the
high­
dose
groups,
one
male
and
one
female
were
found
dead
during
weeks
1
and
2,
respectively
intestinal
lesions
were
found
in
both
animals.
In
addition,
one
male
and
one
female
were
sacrificed
moribund
due
to
self
mutilation
during
weeks
4
and
8,
respectively.
Clinical
signs
of
toxicity
prior
to
death
in
these
animals
were
similar
to
those
described
below.
During
the
recovery
period,
one
high­
dose
male
was
found
dead
during
week
1.
Premature
sacrifice
or
death
of
several
other
animals
was
considered
incidental
to
treatment.
Ophthalmologic
examinations,
gross
necropsy
and
neuropathology
of
surviving
animals
were
unremarkable.
Approximately
4
hours
post­
dosing,
clinical
signs
reported
weekly
throughout
the
study
in
the
high­
dose
males
and
females
included
hunched
posture
(
13
and
14),
labored
breathing
(
14
and
13),
digging
at
cage
(
14
and
14),
salivation
(
15
and
15),
anogenital
staining
(
15
and
15),
dried
material
around
the
nose
and/
or
mouth
(
15
and
15),
colored
material
around
the
eyes
(
13
and
14),
lacrimation
(
13
and
14),
and
rough
coat
(
15
and
15).
Extremely
decreased
activity
was
observed
in
high­
dose
males
and
females
during
the
first
half
of
the
treatment
period,
whereas,
excessive
grooming
(
11
and
14)
and
bulging
eyes
(
13
and
14)
were
more
common
in
the
second
half
of
the
treatment
period.
In
addition,
self
mutilation
was
observed
in
5
males
and
6
females
in
the
highdose
group.
In
the
mid­
dose
males
and
females,
clinical
signs
included
hunched
posture
(
2
and
8),
digging
(
4
and
9),
salivation
(
5
and
5)
and
excessive
grooming
(
6
and
9).
Many
of
these
clinical
signs
in
mid­
and
high­
dose
males
and
females
were
still
present
the
following
morning.
In
the
low­
dose
males
and
females,
excessive
grooming
was
observed
in
5
and
6
animals,
respectively,
and
bulging
eyes
were
observed
in
6/
10
females.
None
of
the
control
animals
showed
any
of
these
signs
with
the
exception
of
bulging
eyes
in
6/
15
control
females.

No
treatment­
related
effects
on
body
weights,
body
weight
gains,
food
consumption
or
neurobehavioral
assessment
were
seen
in
the
low­
and
mid­
dose
females
or
low­
dose
males.
High­
dose
males
had
significantly
(
p

0.01)
lower
body
weights
and
body
weight
gains
compared
with
the
controls
throughout
the
treatment
and
recovery
periods.
Absolute
body
weights
of
the
high­
dose
males
were
80%
of
the
control
level
for
week
1
and
declined
to
67%
of
the
control
level
by
week
13.
The
most
pronounced
effect
on
body
weight
gain
by
the
high­
dose
males
occurred
as
a
weight
loss
for
weeks
1
and
2;
thereafter
body
weight
gains
were
4­
36%
of
the
control
level.
Absolute
body
weights
and
body
weight
gains
of
the
mid­
dose
males
were
not
statistically
different
from
the
controls,
however,
body
weight
gains
were
86­
88%
of
the
control
levels
for
weeks
4­
13.
Mean
absolute
body
weights
of
the
high­
dose
females
were
significantly
(
p

0.05)
less
than
the
controls
during
weeks
1­
3
and
5
(
90­
95%
of
controls).
Body
weight
gains
by
the
high­
dose
females
were
significantly
(
p

0.05
or
0.01)
less
than
the
controls
for
weeks
1
(
weight
loss)
and
3­
6
(
67­
85%
of
controls).
Food
consumption
by
the
high­
dose
males
was
49­
92%
of
the
control
level
during
weeks
1­
10
with
statistical
significance
(
p

0.01)
attained
during
weeks
1­
5,
7,
and
10.
Food
consumption
by
the
high­
dose
females
was
significantly
(
p

0.01)
less
than
the
controls
for
weeks
1
and
3
(
55%
and
84%,
respectively,
of
controls).
No
dose­
or
treatmentrelated
effects
were
noted
in
any
group
for
fore­
and
hind­
limb
grip
strength,
landing
foot
splay,
home
cage
observations,
or
sensorimotor
and
reflex
responses.
During
handling,
the
incidence
rate
of
animals
with
abnormal
fur
(
rough
coat
and
piloerection)
was
increased
in
the
high­
dose
Page
23
of
59
males
and
females
as
noted
during
clinical
observations.
In
the
open
field,
abnormal
posture
was
observed
in
7.69­
21.43%
of
high­
dose
males
and
in
21.43­
38.46%
of
high­
dose
females
compared
with
0.0%
of
the
controls
at
weeks
4­
13.
No
other
dose­
or
treatment­
related
abnormalities
were
observed
in
any
group
during
open
field
evaluations.
Mean
distance
traveled
was
significantly
(
p

0.05
or
0.01)
decreased
in
high­
dose
males
at
weeks
1
and
8
to
61%
and
73%,
respectively,
of
the
control
values.
For
weeks
4
and
13,
the
distance
traveled
by
the
high­
dose
males
was
slightly
less
than
the
controls:
82%
and
90%,
respectively.
The
mean
distance
traveled
by
the
high­
dose
females
was
significantly
(
p

0.05
or
0.01)
less
than
the
controls
throughout
the
treatment
period
(
57­
78%
of
control
value).
Correspondingly,
mean
resting
time
was
significantly
(
p

0.05
or
0.01)
increased
in
high­
dose
males
and
females
to
122­
129%
and
118­
135%,
respectively,
of
the
control
levels.
The
LOAEL
is
2
mg/
kg/
day
based
on
clinical
signs
of
toxicity,
excessive
grooming
in
males
and
females,
and
bulging
eyes
in
females.
The
NOAEL
is
less
than
2
mg/
kg/
day.

This
study
was
previously
classified
as
unacceptable/
guideline
due
to
the
lack
of
a
NOAEL;
however,
the
lack
of
a
NOAEL
does
not
automatically
preclude
an
acceptable
classification,
and
after
reconsideration,
the
team
has
upgraded
the
study
to
Acceptable/
Guideline.
The
study
satisfies
the
guideline
requirement
for
a
series
870.6200
subchronic
neurotoxicity
study
in
rats.
In
making
its
decision
to
upgrade
this
study,
the
team
considered
the
results
of
the
study
together
with
the
results
of
the
rat
chronic
feeding
study.
The
two
studies
taken
together
were
deemed
adequate
to
establish
a
NOAEL
of
0.5
mg/
kg/
day
for
neurotoxic
effects.
See
section
4.4
for
more
detailed
information
on
the
weight­
of­
the­
evidence
approach
used
to
select
doses
and
endpoints
for
tau­
fluvalinate.

4.2.3
Developmental
Toxicity
Studies
A.
Rat
Study.

In
a
developmental
toxicity
study
(
1998,
MRID
44743301),
Tau­
Fluvalinate
(
88.4%
a.
i.,
Lot
#
56613870/
96026)
was
administered
by
gavage
at
0,
5,
10,
or
15
mg/
kg/
day
to
pregnant
Crl:
CD
®
BR
VAF/
Plus
®
rats
(
25/
dose)
on
gestation
days
(
GDs)
6­
19.
Dams
were
sacrificed
on
GD
20.
No
animals
died
during
the
study.

Decreases
(
p

0.05
or
0.01)
in
body
weights
and
body
weight
gains
were
observed
in
the
10
mg/
kg
animals
as
follows:
decreased
mean
body
weights
(

5%,
GD
20);
reduced
body
weights
corrected
for
gravid
uterine
weight
(

6%);
decreased
body
weight
gains
(

17%,
GDs
15­
17);
reduced
body
weight
gains
for
the
overall
treatment
interval
(

17%,
GDs
6­
20)
and
for
the
overall
study
interval
(

13%,
GDs
0­
20);
decreased
body
weight
gains
corrected
for
gravid
uterine
weight
for
the
overall
treatment
interval
(

45%,
GDs
6­
20)
and
for
the
overall
study
interval
(

26%,
GDs
0­
20).
Decreases
(
p

0.05
or
0.01)
in
absolute
(
g/
day)
and
relative
(
g/
kg/
day)
food
consumption
were
noted
in
the
10
mg/
kg
animals
at
GDs
6­
9
(

10­
11%),
GDs
15­
19
(

11­
13%),
for
the
overall
treatment
interval
(

9­
10%,
GDs
6­
20),
and
for
the
overall
study
interval
(

6­
7%,
GDs
0­
20).
At
15
mg/
kg,
clinical
observations
were
limited
to
increased
incidences
of
chromorhinorrhea
(
14/
375
possible
observations
in
8/
25
animals,
p

0.01)
and
urinestained
abdominal
fur
(
7/
375
possible
observations
in
3/
25
animals).
When
compared
to
concurrent
controls,
decreases
(
p

0.05
or
0.01)
in
body
weights
and
body
weight
gains
were
Page
24
of
59
observed
in
the
15
mg/
kg
animals
as
follows:
decreased
mean
body
weights
(

6­
8%,
GDs
18­
20);
reduced
body
weights
corrected
for
gravid
uterine
weight
(

8%);
decreased
gravid
uterine
weights
(

12%,
not
statistically
significant);
decreased
body
weight
gains
(

33%,
GDs
15­
17);
reduced
body
weight
gains
for
the
overall
treatment
interval
(

27%,
GDs
6­
20)
and
for
the
overall
study
interval
(

22%,
GDs
0­
20);
decreased
body
weight
gains
corrected
for
gravid
uterine
weight
for
the
overall
treatment
interval
(

54%,
GDs
6­
20)
and
for
the
overall
study
interval
(

34%,
GDs
0­
20).
Decreases
(
p

0.05
or
0.01)
in
absolute
(
g/
day)
and
relative
(
g/
kg/
day)
food
consumption
were
noted
in
the
15
mg/
kg
animals
beginning
at
GDs
6­
9
and
continuing
throughout
treatment
(

8­
17%),
for
the
overall
treatment
interval
(

12­
15%,
GDs
6­
20),
and
for
the
overall
study
interval
(

7­
10%,
GDs
0­
20).
No
treatment­
related
gross
pathologic
findings
were
noted.
The
number
of
corpora
lutea,
implantations,
resorptions,
percent
males,
and
pre­
and
postimplantation
losses
were
similar
between
control
and
treated
groups.
The
maternal
LOAEL
is
10
mg/
kg/
day
based
on
decreased
body
weights,
body
weight
gains,
and
food
consumption.
The
maternal
NOAEL
is
5
mg/
kg/
day.

There
were
no
treatment­
related
developmental
effects
noted
at
any
dose
level.
The
developmental
LOAEL
was
not
observed.
The
developmental
NOAEL
is

15
mg/
kg/
day.

This
developmental
toxicity
study
is
classified
acceptable
(
§
83­
3[
a])
and
does
satisfy
the
guideline
requirement
for
a
developmental
toxicity
study
in
the
rat.

B.
Rabbit
study.

In
a
developmental
toxicity
study
(
1981,
MRID
No.
00094112,
and
1990,
MRID
No.:
92069054)
Tau­
fluvalinate
technical
(
93.1%,
Run
23­
R,
Batch
#
0281028)
was
administered
in
a
corn
oil
vehicle
by
gavage
at
0,
5,
25,
or
125
mg/
kg/
day
to
pregnant
New
Zealand
White
rabbits
(
17
females/
dose)
on
gestation
days
(
GDs)
6
through
18.
Dams
were
sacrificed
on
GD
29.
One
highdose
female
died
on
Day
16
following
signs
of
labored
respiration,
cyanosis
and
depression.
The
cause
of
death
of
this
female
is
not
readily
apparent
but
was
not
considered
treatment
related.
One
control
animal
and
one
high­
dose
female
were
both
sacrificed
near
the
end
of
"
term"
after
discovery
of
signs
indicating
abortion.
No
unusual
gross
pathology
was
observed
in
either
animal.

Maternal
survival
was
comparable
between
the
control
and
treated
groups.
No
treatment­
related
findings
were
noted
in
the
low­
or
mid­
dose
groups.
In
the
high
dose
group
(
125
mg/
kg/
day),
general
depression
(
17/
17)
was
observed
at
a
greater
incidence
relative
to
controls
(
2/
14).
A
transient
(
statistically
significant)
mean
body
weight
loss
(
13­
14%)
was
noted
for
high­
dose
females
between
Days
6­
18.
The
greater
incidences
of
depression
and
body
weight
loss
in
highdose
females
are
considered
compound­
related.
The
number
of
corpora
lutea,
implantations,
resorptions,
percent
males,
and
pre­
and
post­
implantation
losses
were
similar
between
control
and
treated
groups.
The
maternal
LOAEL
is
125
mg/
kg
bw/
day,
based
on
general
depression
and
a
decrease
in
body
weight.
The
maternal
NOAEL
is
25
mg/
kg
bw/
day.

No
treatment­
related
differences
in
fetal
weights
and
lengths
were
observed.
Accompanying
the
maternal
toxicity
in
the
high
dose
group
were
embryo
or
fetotoxic
effects,
higher
incidence
of
resorption
(
40.2%
vs.
22.6%
in
controls),
and
concurrent
lower
fetal
viability
(
59.8%
vs.
76.7%
Page
25
of
59
in
controls).
These
effects
were
not
statistically
significant,
but
were
large
and
consistent,
and
are
considered
to
be
related
to
the
administration
of
compound
and
a
secondary
effect
of
maternal
toxicity.
The
number
and
incidence
of
visceral
anomalies
and
variants
were
not
statistically
different
between
groups.
The
incidence
of
skeletal
anomalies
were
increased
in
the
high
dose
group
as
a
result
of
fetuses
in
one
litter
having
short
and
spatulate
ribs
(
5
rabbits),
short
and
curved
femurs
(
5
rabbits),
and
a
curved
tibia
and
fibula
(
4
rabbits).
A
total
of
10
litters
and
55
fetuses
were
examined
at
the
high
dose.
The
developmental
LOAEL
is
125
mg/
kg/
day,
based
on
higher
incidence
of
resorption
and
concurrent
lower
fetal
viability
and
evidence
of
skeletal
variants.
The
developmental
NOAEL
is
25
mg/
kg/
day.

The
developmental
toxicity
study
in
the
rabbit
is
classified
acceptable/
guideline
(
83­
3[
a])
and
satisfies
the
guideline
requirement
for
a
developmental
toxicity
study
(
OPPTS
870.3700;
OECD
414)
in
rabbits.

4.2.4
Reproductive
Toxicity
Study
In
a
2­
generation
reproduction
study
(
1986,
MRID
44596601),
tau­
fluvalinate
(
93.1%
a.
i.)
was
continuously
administered
in
the
diet
to
Sprague­
Dawley
rats
(
P
generation
­
28/
sex/
dose,
32/
sex/
dose
at
the
high­
dose;
F
1
generation
­
24/
sex/
dose)
at
dose
levels
of
0,
10,
25
or
125
ppm
(
equivalent
to
[
M/
F]
0/
0,
0.76/
0.84,
1.90/
2.08,
and
9.53/
10.51
mg/
kg/
day,
respectively).
Exposure
to
P
animals
began
at
6
weeks
of
age
and
lasted
for
10
weeks
prior
to
mating
and
throughout
mating,
gestation,
and
lactation.
F
1
pups
selected
to
produce
the
F
2
generation
were
exposed
to
the
same
dosage
as
their
parents
at
post­
natal
day
(
PND)
21
and
continuously
throughout
the
rest
of
the
study.
After
approximately
12
weeks
of
treatment,
F
1
offspring
were
paired
to
produce
the
F
2
litters
that
were
necropsied
at
weaning.
Mating
to
produce
a
second
F
2b
generation
was
not
performed.

Systemic
toxicity.
There
were
no
differences
of
toxicological
concern
in
body
weight,
body
weight
gain,
food
consumption,
female
sexual
development,
reproductive
performance,
gross
pathologic
findings,
absolute
and
body
weight­
adjusted
organ
weights,
and
histological
findings.
At
125
ppm,
treatment­
related
clinical
signs
were
limited
to
skin
ulceration
in
P
males
(
3/
32
treated
vs
0/
28
controls),
P
females
(
1/
32
treated
vs
0/
28
controls),
and
F
1
males
(
2/
24
treated
vs
0/
24
controls).
The
P
female
and
her
litter
were
severely
ulcerated
and,
therefore,
were
sacrificed.
F
1
dams
did
not
exhibit
any
treatment­
related
clinical
signs.
No
observations
of
toxicological
significance
were
made
at
the
mid­
(
25
ppm)
and
low­
dose
(
10
ppm).
The
systemic
toxicity
LOAEL
is
125
ppm
(
9.53/
10.51
[
M/
F]
mg/
kg/
day)
based
on
clinical
signs
(
skin
ulceration).
The
systemic
toxicity
NOAEL
is
25
ppm
(
1.90/
2.08
[
M/
F]
mg/
kg/
day).

Offspring
toxicity.
There
were
no
differences
of
toxicological
concern
in
litter
size,
viability,
developmental
landmarks,
gross
pathologic
findings,
absolute
and
body
weight­
adjusted
organ
weights,
and
histological
findings.
At
125
ppm,
tremors
were
observed
during
the
lactation
period
(

LD
14)
in
the
F
1
litters
(
15/
28
treated
litters
vs
0/
28
controls)
and
F
2
litters
(
6/
20
treated
litters
vs
1/
24
controls).
There
was
a
toxicologically
significant
decrease
in
F
2
pup
weight
at
PND
21
(

12%,
p<
0.05).
This
decrease
in
pup
weight,
combined
with
a
slightly
lower
litter
size,
caused
a
significant
decrease
(

16%,
p<
0.05)
in
mean
litter
weight
when
compared
to
controls
(
286.9
g
treated
vs
342.1
g
controls).
No
observations
of
toxicological
significance
were
made
Page
26
of
59
in
the
10
or
25
ppm
groups.
The
offspring
toxicity
LOAEL
is
125
ppm
(
9.53/
10.51
[
M/
F]
mg/
kg/
day)
based
on
decreased
pup
body
weights
and
increased
incidence
of
clinical
signs
(
tremors).
The
reproductive
toxicity
NOAEL
is
25
ppm
(
1.90/
2.08
[
M/
F]
mg/
kg/
day).

The
reproductive
study
is
determined
to
be
acceptable/
guideline
(
§
83­
4)
and
does
satisfy
the
guideline
requirement
for
a
multi­
generational
reproductive
toxicity
study
in
rats.

4.2.5
Additional
Information
from
Literature
Sources
A
literature
search
(
PubMed)
revealed
one
paper
(
J.
Steroid
Biochem.
35(
3­
4):
409­
414
(
1990))
suggesting
that
pyrethroids
as
a
class
(
including
tau­
fluvalinate)
may
have
endocrine
disrupting
properties
based
on
inhibition
of
[
3H]
methyltrienolone
binding
with
human
skin
fibroblasts
androgen
receptors.
Not
all
pyrethroids
tested,
however,
were
able
to
displace
[
3H]
testosterone
from
sex
hormone
binding
globulin.
Although
tau­
fluvalinate
is
not
mentioned
specifically,
another
publication
(
Sheets
et
al,
Toxicolo.
Appl.
Pharmacol.
126:
186­
190
(
1994))
discusses
the
inability
of
the
neonatal
rats
to
detoxify
pyrethroids.

4.2.6
Pre­
and/
or
Postnatal
Toxicity
4.2.6.1
Determination
of
Susceptibility
Neither
the
rat
or
rabbit
developmental
toxicity
nor
the
rat
multi­
generation
reproduction
studies
demonstrated
increased
toxicity
to
the
fetuses
or
offspring
relative
to
the
dams
or
parental
generation,
as
indicated
by
the
offspring
having
LOAELs
greater
than
or
equal
to
the
parental
LOAELs.
In
particular,
the
NOAEL
and
LOAEL
for
maternal
toxicity
in
the
rat
developmental
toxicity
study
were
5
and
10
mg/
kg/
day,
whereas
there
was
no
developmental
toxicity
at
15
mg/
kg/
day,
the
highest
dose
tested.
The
NOAEL
and
LOAEL
for
both
the
maternal
and
developmental
toxicity
for
the
rabbit
developmental
toxicity
study
were
25
and
125
mg/
kg/
day.
However,
the
developmental
effects
at
125
mg/
kg/
day
or
signs
of
lower
fetal
viability
and
evidence
of
skeletal
variants
were
considered
to
accompany
the
lower
body
weight
seen
in
the
dams.
Similarly,
the
NOAEL
and
LOAEL
for
the
systemic
effects
in
the
parental
groups
was
the
same
as
the
NOAEL
and
LOAEL
for
the
offspring
toxicity
in
the
multi­
generation
reproduction
study.
The
degree
of
effects
in
the
offspring
was
not
considered
severe
enough
to
determine
that
there
is
a
meaningful
concern
that
the
offspring
are
qualitatively
more
susceptible
than
the
parents.

Thus,
there
is
no
evidence
of
increased
qualitative
or
quantitative
susceptibility
of
offspring
to
the
toxic
effects
of
tau­
fluvalinate
in
the
available
database.

4.2.6.2
Degree
of
Concern
Analysis
and
Residual
Uncertainties
for
Pre
and/
or
Post­
natal
Susceptibility
The
team
has
concluded
that
there
is
a
low
degree
of
concern
for
residual
uncertainties
for
preand
post­
natal
susceptibility.
There
is
no
evidence
of
increased
susceptibility
in
the
guideline
developmental
or
reproductive
studies.
The
team
has
selected
an
endpoint
for
risk
assessment
that
provides
a
clear
NOAEL
for
the
primary
effect
of
interest,
neurotoxicity.
It
is
the
most
conservative
(
lowest)
endpoint
in
the
database
and
will
be
protective
of
other
effects
seen
in
the
Page
27
of
59
database,
and
any
potential
effects
seen
in
a
DNT
study.
Further,
although
tau­
fluvalinate
is
a
neurotoxicant
and
there
is
no
developmental
neurotoxicity
study
available,
the
team
has
determined
that
the
potential
for
exposure
of
mothers,
their
fetuses
and
neonates
to
taufluvalinate
is
low
based
on
the
following:

1)
Tau­
fluvalinate
has
very
limited
annual
domestic
usage,
and
the
majority
of
this
usage
is
in
commercial
greenhouses
and
on
outdoor
field­
and
container­
grown
ornamentals
where
pregnant
women
and
babies
are
unlikely
to
be
exposed.

2)
Dietary
exposures
to
tau­
fluvalinate
are
anticipated
to
be
very
low
to
insignificant,
as
the
only
registered
food
use
of
tau­
fluvalinate
is
in
beehives
(
honey).
Honey
is
not
used
as
an
ingredient
in
infant
formulas
and
is
not
considered
an
appropriate
food
for
children
less
than
2
years
old.
In
addition,
the
low
solubility
(
2.4
ppb)
of
tau­
fluvalinate
limits
the
likelihood
of
it
getting
into
drinking
water
in
appreciable
quantities.
The
results
of
acute
and
chronic
dietary
exposure
analyses
conducted
using
DEEM­
FCID
and
Lifeline
software
confirm
tau­
fluvalinate's
low
dietary
exposure
potential
(
See
section
6.1.2
below).

3)
The
potential
for
residential
exposure
is
very
low,
based
on
the
low
annual
usage
on
residential
sites
and
the
fact
that
there
are
no
broadcast
applications
allowed
in
residential
areas.

Based
on
tau­
fluvalinate's
limited
use
and
the
low
probability
of
exposure,
the
team
has
a
low
degree
of
concern
for
pre­
and/
or
post­
natal
increased
sensitivity.
Additional
information
supporting
this
conclusion,
including
specific
production
and
usage
data,
is
contained
in
the
Confidential
Appendix.

4.3
Recommendation
for
a
Developmental
Neurotoxicity
Study
The
RARC
met
on
02/
09/
2005
and
considered
the
factors
that
both
support
and
do
not
support
requiring
a
developmental
neurotoxicity
study
as
described
below.
After
consideration
of
these
factors
as
well
as
the
exposure
patterns,
the
RARC
agreed
that
there
would
not
be
a
sufficient
exposure
to
justify
requiring
a
developmental
neurotoxicity
study
with
tau­
fluvalinate
(
Taufluvalinate
Proposed
Review
and
Risk
Assessment
Strategy
Report
of
the
Risk
Assessment
Review
Committee
(
RARC1),
Feb.
9,
2005).

4.3.1
Evidence
that
supports
requiring
a
Developmental
Neurotoxicity
study
Tau­
Fluvalinate
is
a
pyrethroid
insecticide
with
known
effects
on
the
nervous
system
in
insects.
In
mammals
manifestations
of
neurotoxicity
resulting
from
interaction
with
the
sodium
channel
(
and
possibly
other
nerve
membrane
phenomena)
can
result.
Since
the
fetus
and
neonatal
mammals
have
a
lower
capacity
for
detoxifying
the
intact
pyrethroid
structure,
there
is
a
potential
for
neurotoxicity
to
result
in
fetuses
if
the
intact
pyrethroid
passes
the
placenta
or
if
intact
pyrethroid
can
be
transported
to
the
newborn
mammal
via
lactation.
Although
residues
of
intact
pyrethroid
in
infant
formula
could
result
in
exposure
of
newborns,
there
are
currently
no
food
uses
of
tau­
fluvalinate
likely
to
result
in
such
residues.
Honey,
the
only
food
on
which
tau­
fluvalinate
is
used,
is
not
a
component
of
infant
formula.
Page
28
of
59
Tau­
fluvalinate
was
shown
to
cause
peripheral
nerve
histological
changes
in
the
non­
guideline
"
acute"
neurotoxicity
study.

Developmental
neurotoxicity
studies
have
been
requested
for
most
other
pyrethroids.

4.3.2
Evidence
that
supports
not
requiring
Developmental
Neurotoxicity
study
For
the
reasons
described
above
in
section
4.2.6.2
(
Degree
of
Concern
Analysis
and
Residual
Uncertainties
for
Pre
and/
or
Post­
natal
Susceptibility)
the
team
has
determined
that
the
potential
for
exposure
of
mothers,
their
fetuses
and
neonates
to
tau­
fluvalinate
is
low
and
not
significant
enough
to
justify
requiring
a
developmental
neurotoxicity
study.
Total
domestic
usage
is
very
limited,
and
most
of
this
use
occurs
on
non­
food,
non­
residential
sites
where
exposure
of
pregnant
women
and
infants
would
not
be
expected.
Significant
dietary
exposure
is
not
expected,
based
on
tau­
fluvalinate's
limited
usage,
low
potential
to
contaminate
drinking
water
and
the
fact
that
honey
(
the
only
food
use)
is
not
a
component
of
infant
formula
and
not
recommended
for
consumption
by
children
under
2
years
of
age.

In
addition,
the
conduct
of
a
DNT
study
with
tau­
fluvalinate
would
be
confounded
by
the
increased
sensitivity
of
the
rats
to
the
"
pyrethroid
reaction".
The
severity
of
the
dermal
irritation
that
results
from
this
reaction
often
requires
early
termination
of
the
study.
Such
confounding
would
further
affect
the
assessment
of
the
neonatal
pups
who
may
be
in
dermal
contact
with
the
intact
test
material
via
proximity
to
spilled
feed.
The
dams
and
pups
would
have
to
be
dosed
by
gavage
in
an
attempt
to
circumvent
confounding
of
the
study
due
to
the
"
pyrethroid
reaction".

4.3.2.1
Rationale
for
the
UFDB
(
when
a
DNT
is
recommended)

Not
applicable.
A
DNT
study
is
not
recommended.

4.4
Hazard
Identification
and
Toxicity
Endpoint
Selection
Comments
about
endpoint
selection:
Based
on
a
weight­
of­
evidence
approach,
a
conservative
NOAEL
for
neurotoxic
effects
has
been
identified
for
tau­
fluvalinate.
This
approach
is
based
on
the
results
of
2
studies:
the
rat
chronic
feeding
study
and
the
rat
subchronic
neurotoxicity
study.
In
the
chronic
study
in
the
rat,
clinical
signs
of
neurotoxicity
including:
excessive
salivation,
pawing
at
bottom
of
the
cage,
lacrimation,
abnormal
stance,
ruffling,
and
transient
hyperactivity
followed
by
hypoactivity
were
observed
at
1.0
mg/
kg/
day;
these
effects
were
not
seen
at
0.5
mg/
kg/
day.
In
the
subchronic
study
in
the
rat,
excessive
grooming
and
bulging
eyes
were
noted
in
the
animals
at
2
mg/
kg/
day
(
the
lowest
dose
tested).
We
evaluated
these
two
studies
in
parallel
because
the
clinical
signs
of
neurotoxicity
in
the
rat
chronic
study
are
transient
and
mentioned
in
the
report
but
not
well
documented.
However,
the
team
believes
that
these
early­
onset
neurotoxic
effects
are
consistent
with
the
typical
clinical
signs
associated
with
pyrethroids
and
are
most
likely
the
result
of
preliminary
nerve
stimulation
and/
or
agitation.
At
the
next
highest
dose
tested
in
the
chronic
rat
study
(
2.5
mg/
kg/
day),
the
development
of
tropic
(
plantar)
ulcers
could
possibly
be
indicative
of
amplified
and
prolonged
nervous
system
stimulation/
agitation.
Furthermore,
the
results
of
the
90­
day
subchronic
neurotoxicity
study
are
consistent
with
the
Page
29
of
59
results
of
the
rat
chronic
feeding
study,
demonstrating
marked
evidence
of
neurotoxicity
at
a
similar
low
dose.
The
team
believes
that
the
results
of
these
2
studies
taken
together
form
the
basis
for
a
clear
NOAEL
of
0.5
mg/
kg/
day
for
neurotoxic
effects,
with
minimal
effects
beginning
to
be
seen
at
1.0
mg/
kg/
day
in
the
chronic
study,
thus
establishing
a
conservative
LOAEL.
The
selection
of
this
LOAEL
is
further
supported
by
the
increasingly
severe
neurotoxic
effects
seen
at
the
higher
doses
of
2
mg/
kg/
day
and
2.5
mg/
kg/
day,
respectively,
in
the
shorter­
term
subchronic
study
and
longer­
term
chronic
feeding
study.
We
believe
that
this
conservative
determination
is
protective
for
all
population
subgroups.

4.4.1
Acute
Reference
Dose
(
aRfD)
­
General
Population
Studies
Selected:
Rat
Chronic
Feeding
Study
&
Subchronic
Neurtotoxicity
Study
in
the
rat
(
See
rationale
Section
4.4)

MRID
No:
92069048
&
44900601
Executive
Summaries:

Rat
Chronic
Feeding
Study:
In
a
combined
chronic
/
carcinogenicity
study
(
1984,
MRID
92069048),
tau­
fluvalinate
(
92.1%
a.
i,
Run
23R,
Batch
No.
0281028)
was
administered
to
Charles
Rivers
CD
rats
(
85/
sex/
dose)
by
gavage
at
dose
levels
of
0,
0.25,
0.50,
1.0,
or
2.5
mg/
kg
bw/
day
for
24
months.

In
males
and
females
from
groups
receiving
1.0
and
2.5
mg/
kg/
day,
transient
clinical
signs
of
toxicity
included
excessive
salivation
and
lacrimation,
pawing
of
the
bottom
and
sides
of
the
cage,
abnormal
stance,
ruffling,
and
transient
hyperactivity
followed
by
hypoactivity.
These
signs
were
observed
during
the
first
3
hours
after
dosing
and
subsided
within
6
hours.
No
treatment­
related
effects
on
hematology,
urinalysis,
ophthalmology,
clinical
chemistry
or
organ
weights
were
observed
in
male
or
female
rats
at
any
dose.
Mean
body
weights
were
significantly
decreased
(
13­
15%)
in
females
receiving
2.5
mg/
kg/
day.
There
were
no
effects
of
dosing
on
food
consumption.
There
was
an
increase
in
plantar
ulcers
in
females
receiving
2.5
mg/
kg/
day
when
compared
to
controls.
No
other
treatment­
related
effects
on
gross
or
histopathology
were
observed
at
any
dose.
At
the
doses
tested,
there
were
no
treatment­
related
increases
in
tumor
incidences
in
treated
animals
when
compared
with
controls.
The
LOAEL
is
1.0
mg/
kg/
day,
based
on
abnormal
stance,
ruffling,
and
transient
hyperactivity
followed
by
hypoactivity
in
males
and
females.
The
NOAEL
is
0.50
mg/
kg/
day
.

This
chronic/
carcinogenicity
study
in
the
rat
is
classified
as
acceptable/
guideline
and
satisfies
the
guideline
requirement
for
a
chronic/
carcinogenicity
study
[
OPPTS
870.4300);
OECD
453]
in
the
rat.

Subchronic
Neurotoxicity
Rat
Study
­
See
executive
summary
of
this
study
in
Section
4.2.2
Dose
and
Endpoint
for
Risk
Assessment:
NOAEL
=
0.5
mg/
kg/
day
based
on
excessive
salivation
and
lacrimation,
pawing
of
the
bottom
and
sides
of
the
cage,
abnormal
stance,
ruffling,
and
transient
hyperactivity
followed
by
hypoactivity
at
1.0
mg/
kg/
day
(
LOAEL).
Page
30
of
59
Uncertainty
Factor(
s):
100.
Includes
a
10X
factor
for
interspecies
extrapolation
and
a
10X
factor
for
intraspecies
variation.

Comments
about
Study/
Endpoint:
See
explanation
above
in
Section
4.4.
On
February
9th,
2005,
the
RARC
concurred
that
the
results
of
the
90­
day
neurotoxicity
study
are
consistent
with
the
results
of
the
chronic
study
and
that
the
NOAEL
from
the
rat
chronic
feeding
study
should
be
used
for
acute,
chronic
and
inhalation
endpoints.
The
acute,
short­
term,
intermediate­
term
and
long­
term
effects
of
tau­
fluvalinate
are
not
cumulative
based
on
the
characteristics
and
nature
of
typical
pyrethroid
effects.
Furthermore,
the
RARC
concurred
that
even
though
tau­
fluvalinate
is
a
neurotoxicant,
the
low
exposure
precludes
the
need
to
require
a
DNT.

Acute
RfD
=
0.5
mg/
kg/
day
(
NOAEL)
=
0.005
mg/
kg/
day
100
(
UF)

4.4.2
Acute
Reference
Dose
(
aRfD)
­
Females
age
13­
49
The
acute
RfD
for
females
age
13­
49
is
the
same
as
for
the
general
population
(
see
above).

4.4.3
Chronic
Reference
Dose
(
cRfD)

Studies
Selected:
Same
as
for
acute
dietary
(
Rat
Chronic
Feeding
Study
&
Subchronic
Neurtotoxicity
Studies
(
See
rationale
Section
4.4).

MRID
No:
92069048
&
44900601
Executive
Summaries:
See
above.

Dose
and
Endpoint
for
Risk
Assessment:
NOAEL
=
0.5
mg/
kg/
day
based
on
excessive
salivation
and
lacrimation,
pawing
of
the
bottom
and
sides
of
the
cage,
abnormal
stance,
ruffling,
and
transient
hyperactivity
followed
by
hypoactivity
at
1.0
mg/
kg/
day
(
LOAEL).

Uncertainty
Factor(
s):
100.
Includes
a
10X
factor
for
interspecies
extrapolation
and
a
10X
factor
for
intraspecies
variation.

Comments
about
Study:
See
section
4.4.1
Chronic
RfD
=
0.5
mg/
kg/
day
(
NOAEL)
=
0.005
mg/
kg/
day
100
(
UF)
Page
31
of
59
4.4.4
Incidental
Oral
Exposure
(
Short
and
Intermediate
Term)

Short­/
Intermediate­
term
oral
endpoints
are
selected
when
incidental
oral
exposure
could
result
from
residential,
recreational,
and
institutional
pesticide
use.
Based
on
the
limited
usage
of
taufluvalinate
and
the
nature
of
the
currently
registered
uses,
the
potential
for
incidental
oral
exposure
to
tau­
fluvalinate
is
very
low.
Tau­
fluvalinate
is
registered
for
use
in
residential
areas
as
a
perimeter
treatment
around
buildings
and
as
an
ant
mound
drench.
Because
of
the
localized
nature
of
these
uses,
neither
would
be
expected
to
result
in
significant
incidental
oral
exposure.
There
are
no
broadcast
or
other
wide
area
uses
of
tau­
fluvalinate
permitted
on
residential,
recreational
or
institutional
sites.
Based
on
these
considerations,
the
team
concluded
that
an
incidental
oral
exposure
endpoint
was
not
required.
The
RARC
concurred
with
the
team's
decision
(
Tau­
fluvalinate:
Proposed
Review
and
Risk
Assessment
Strategy
Report
of
the
Risk
Assessment
Review
Committee
(
RARC1),
Feb.
9,
2005)

4.4.5
Dermal
Absorption
There
is
no
acceptable
guideline
study
that
demonstrates
a
dermal
absorption
factor.
There
is
one
study
(
Accession
No.:
250142,
classified
as
unacceptable/
guideline,
not
ungradable)
that
demonstrated
that
only
4%
of
the
applied
dose
was
absorbed
in
a
single
male
rat.
Comparison
of
the
LOAEL
of
125
mg/
kg/
day
(
based
on
"
anorexia
and
general
depression")
from
the
rabbit
developmental
toxicity
study
with
the
LOAEL
of
500
mg/
kg/
day
(
based
on
systemic
response
of
decreased
food
consumption)
from
the
21­
day
dermal
toxicity
study
would
suggest
that
a
dermal
absorption
factor
of
25%
(
125
mg/
kg/
day
÷
500
mg/
kg/
day
x
100)
would
be
appropriate.

4.4.6
Dermal
Exposure
(
Short,
Intermediate
and
Long
Term)

No
toxicity
endpoint
was
selected
for
dermal
exposure
to
products
containing
tau­
fluvalinate.
Dermal
exposure
to
products
containing
tau­
fluvalinate
is
expected
to
be
largely
self­
limiting
due
to
the
irritation
that
occurs
as
a
result
of
the
"
pyrethroid
reaction".
The
team
determined
(
and
the
RARC
agreed)
that
the
issue
of
dermal
exposure
can
be
best
addressed
by
labeling
to
avoid
contact
with
skin
and
instructions
to
wash
the
affected
area
immediately
following
contact.
Currently
approved
end­
use
product
labels
include
adequate
precautionary
labeling.

4.4.7
Inhalation
Exposure
(
Short,
Intermediate
and
Long
Term)

Studies
Selected:
Same
as
for
acute
and
chronic
dietary
(
Rat
Chronic
Feeding
Study
&
Subchronic
Neurtotoxicity
Studies
(
See
rationale
Section
4.4).

MRID
No:
92069048
&
44900601
Executive
Summaries:
See
above.

Dose
and
Endpoint
for
Risk
Assessment:
NOAEL
=
0.5
mg/
kg/
day
based
on
excessive
salivation
and
lacrimation,
pawing
of
the
bottom
and
sides
of
the
cage,
abnormal
stance,
ruffling,
and
transient
hyperactivity
followed
by
hypoactivity
at
1.0
mg/
kg/
day
(
LOAEL).
Page
32
of
59
Comments
about
Study:
See
section
4.4.1.
There
is
no
subchronic
inhalation
study
with
taufluvalinate
available
for
risk
assessment.
The
potential
for
tau­
fluvalinate
to
affect
the
respiratory
system
in
humans
through
its
ability
to
cause
the
"
pyrethroid
reaction"
has
not
been
assessed
in
animal
studies.
Even
if
it
were,
the
most
appropriate
species
for
assessing
the
potential
human
hazard
due
to
possible
respiratory
effects
may
not
be
the
rat,
the
species
commonly
used
and
recommended
by
the
guidelines
for
subchronic
inhalation
studies.
The
potential
for
taufluvalinate
to
affect
the
respiratory
system
in
humans
is
an
important
issue
because
humans
with
chronic
respiratory
conditions
such
as
asthma
or
emphysema
may
have
incidents
triggered
by
exposure
to
tau­
fluvalinate.
The
RARC
recommended
that
label
restrictions
be
such
that
applicators
and
workers
wear
appropriate
respirators
when
applying
products
that
may
result
in
spray
mists
or
other
inhalation
hazards.
Currently
approved
product
labels
require
adequate
protective
clothing,
including
a
NIOSH­
approved
respirator
for
both
indoor
and
outdoor
applications.

4.4.8
Margins
of
Exposure
The
following
margins
of
exposure
(
MOEs)
represent
HED's
level
of
concern
for
occupational
and
residential
(
non­
dietary)
exposure
risk
assessments:

Route
of
Exposure
Occupational
MOE
(
all
durations
of
exposure)
Residential
MOE
(
all
durations
of
exposure)

Dermal
100
(
this
risk
assessment
is
not
required)
100
(
this
risk
assessment
is
not
required)

Incidental
Oral
100
(
this
risk
assessment
is
not
required)
100
(
this
risk
assessment
is
not
required)

Inhalation
100
100
(
this
risk
assessment
is
not
required)

For
occupational
exposure
(
all
durations)
risk
assessments,
an
MOE
of
100
is
required.
The
MOE
is
based
on
10x
for
intraspecies
variation
and
10x
for
interspecies
extrapolation.
For
residential
exposures,
an
MOE
of
100
is
required,
and
is
based
on
10x
for
intraspecies
variation,
10x
for
interspecies
extrapolation
and
a
1x
special
FQPA
factor.

4.4.9
Recommendation
for
Aggregate
Exposure
Risk
Assessments
Exposures
resulting
from
oral
and
inhalation
exposure
may
be
aggregated
based
on
a
common
toxic
endpoint:
neurotoxicity.
Neither
an
incidental
oral
endpoint
nor
a
dermal
endpoint
was
selected
for
risk
assessment,
and
there
is
no
need
to
aggregate
exposures
through
these
routes
with
oral
(
dietary)
and
inhalation
exposures.

4.4.10
Classification
of
Carcinogenic
Potential
Tau­
fluvalinate
was
not
demonstrated
to
be
carcinogenic
in
either
the
rat
or
mouse
carcinogenicity
studies,
and
none
of
the
mutagenicity/
genetic
toxicity
studies
were
determined
to
be
positive.
Based
on
lack
of
carcinogenic
effects
in
the
rat
and
mouse
carcinogenicity
studies
Page
33
of
59
and
lack
of
a
mutagenicity
concern,
tau­
fluvalinate
can
be
classified
as
"
not
likely
to
be
a
human
carcinogen".

Table
4.4.
Summary
of
Toxicological
Doses
and
Endpoints
for
Tau­
fluvalinate
for
Use
in
Human
Risk
Assessments
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
Special
FQPA
SF*
and
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
Acute
Dietary
(
females
13­
49)
No
selection.
No
evidence
that
there
is
significant
toxicity
following
a
single
exposure.

Acute
Dietary
(
general
population)
NOAEL
=
0.5
mg/
kg/
day.
UF
=
100
aRfD
=
0.005
mg/
kg/
day
1X
aPAD
=
aPAD/
FQPA
SF
aPAD
=
0.005/
1
=
0.005
mg/
kg/
day
LOAEL
=
1
mg/
kg/
day.
Clinical
signs
in
the
rat
chronic
feeding
study
coupled
with
a
LOAEL
of
2
mg/
kg/
day
based
on
excessive
grooming
and
bulging
eyes
in
the
subchronic
neurotoxicity
study.

Chronic
Dietary
(
all
populations)
NOAEL
=
0.5
mg/
kg/
day
UF
=
100
cRfD
=
0.005
mg/
kg/
day
1X
cPAD
=
cRfD/
FQPA
SF
cPAD
=
0.005/
1
=
0.005
mg/
kg/
day
LOAEL
=
1
mg/
kg/
day.
Clinical
signs
in
the
rat
chronic
feeding
study
coupled
with
a
LOAEL
of
2
mg/
kg/
day
based
on
excessive
grooming
and
bulging
eyes
in
the
subchronic
neurotoxicity
study.

Incidental
Oral
­
all
durations.
No
selection
since
there
are
no
residential,
recreational
or
institutional
uses
likely
to
result
in
incidental
oral
exposure
to
tau­
fluvalinate.
As
per
e­
mail
from
K.
Rothwell
(
February
4,
2005)
there
is
no
residential
turf
use.

Dermal
­
all
intervals
No
endpoint
selection.
Dermal
exposure
should
be
self­
limiting
because
of
the
dermal
reactions
resulting
from
contact
with
product.
The
issue
of
dermal
exposure
can
be
best
addressed
by
labeling
to
avoid
contact
with
skin
and
instructions
to
wash
the
affected
area
immediately
following
contact.

Inhalation
­
all
intervals
Short­
Term
(
1
­
30
days)
NOAEL
=
0.5
mg/
kg/
day.
1X
MOE
=
100
LOAEL
=
1
mg/
kg/
day.
Clinical
signs
in
the
rat
chronic
feeding
study
coupled
with
a
LOAEL
of
2
mg/
kg/
day
based
on
excessive
grooming
and
bulging
eyes
in
the
subchronic
neurotoxicity
study.

Cancer
(
oral,
dermal,
inhalation)
Classification:
tau­
fluvalinate
has
not
been
reviewed
by
CARC
or
HIARC
for
carcinogenicity
classification.
However,
since
no
evidence
of
carcinogenicity
was
seen
in
rat
and
mouse
carcinogenicity
studies
with
tau­
fluvalinate,
and
the
available
mutagenicity/
genetic
toxicity
data
base
do
not
indicate
a
concern,
tau­
fluvalinate
may
be
classified
as
"
not
likely
to
be
a
human
carcinogen".

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
*
Refer
to
Section
4.5
4.5
Special
FQPA
Safety
Factor
The
team
evaluated
the
potential
for
increased
susceptibility
of
infants
and
children
from
exposure
to
tau­
fluvalinate
as
required
by
the
Food
Quality
Protection
Act
(
FQPA)
of
1996
according
to
Page
34
of
59
the
2002
OPP
10x
Guidance
Document.
The
team
concluded
that
the
special
FQPA
SF
can
be
removed
(
1X)
since
there
are
no/
low
concerns
and
no
residual
uncertainties
for
pre­
and/
or
postnatal
toxicity
based
on
the
following
evidence:

°
In
the
developmental
rat
study,
maternal
toxicity
(
decreased
body
weight
and
food
consumption)
was
observed
at
10
mg/
kg/
day.
However,
fetal
anomalies
were
not
seen
at
the
highest
dose
tested
(
15
mg/
kg/
day)
indicating
that
there
is
no
quantitative
or
qualitative
pre­
and/
or
postnatal
toxicity
resulting
from
exposure
to
tau­
fluvalinate.

°
A
clear
NOAEL/
LOAEL
was
established
for
the
developmental
rabbit
study.

°
In
the
2­
generation
reproductive
study
in
rats,
the
fetal
anomalies
(
tremors
during
lactation
in
both
litters,
decrease
in
pup
weight
in
F2
generation
and
slightly
lower
litter
size)
were
seen
only
at
the
highest
dose
tested
(
9.53/
10.51
mg/
kg/
day
for
males/
females),
and
they
were
observed
in
the
presence
of
maternal
toxicity
(
skin
ulcerations).
The
effects
in
the
offspring,
although
not
also
seen
in
the
parents,
demonstrated
a
clear
NOAEL
and
LOAEL
and
are
considered
a
qualitative
increase
in
susceptibility
of
low
concern.

The
tau­
fluvalinate
risk
assessment
team
evaluated
the
quality
of
the
exposure
data;
and,
based
on
these
data,
recommended
that
the
special
FQPA
SF
be
reduced
to
1X.
The
recommendation
is
based
on
the
following:

°
The
dietary
food
exposure
assessment
utilizes
tolerance
level
residues
and
100%
crop
treated
information
for
all
commodities.
By
using
these
screening­
level
assumptions,
chronic
exposures/
risks
will
not
be
underestimated.

°
The
dietary
drinking
water
assessment
utilizes
values
generated
by
models
and
associated
modeling
parameters
which
are
designed
to
provide
conservative,
health
protective,
highend
estimates
of
water
concentrations.

4.6
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).
Page
35
of
59
In
the
available
toxicity
studies
on
tau­
fluvalinate
submitted
for
registration
purposes,
there
was
no
estrogen,
androgen,
and/
or
thyroid
mediated
toxicity.
When
the
appropriate
screening
and/
or
testing
protocols
being
considered
under
the
Agency's
EDSP
have
been
developed,
taufluvalinate
may
be
subjected
to
further
screening
and/
or
testing
to
better
characterize
effects
related
to
endocrine
disruption.

5.0
Public
Health
Data
Reference:
Review
of
Fluvalinate
Incident
Reports,
DP
Barcode
D300199,
Jerome
Blondell,
03/
14/
2005
5.1
Incident
Reports
Databases
for
the
OPP
Incident
Data
System
(
IDS),
Poison
Control
Centers,
the
California
Department
of
Pesticide
Regulation,
the
National
Pesticide
Telecommunications
Network
(
NPTN)
and
the
National
Institute
of
Occupational
Safety
and
Health's
Sentinel
Event
Notification
System
for
Occupational
Risks
(
NIOSH
SENSOR)
were
consulted
for
incident
data
involving
the
insecticidal
active
ingredient
tau­
fluvalinate.

From
the
available
incident
data
it
is
apparent
that
tau­
fluvalinate
exposure
can
lead
to
mild
or
moderate
irritation
of
eyes
and
skin.
Commonly
reported
systemic
effects
include
headache,
nausea
and
breathing
difficulty.
Many
of
the
incidents
reported
in
California
were
related
to
the
pesticide's
use
in
greenhouses.
In
addition,
beekeepers
nationwide
have
reported
dermal
or
other
allergic­
type
reactions.
In
a
comparison
of
Poison
Control
Centers'
data
for
tau­
fluvalinate
and
other
pesticides,
tau­
fluvalinate
was
found
to
be
as
likely
to
cause
minor
symptoms
as
other
pesticides
in
the
database
but
much
less
likely
to
cause
serious
effects
requiring
hospitalization
or
critical
care.

5.2
Other
Tau­
fluvalinate
is
not
included
in
the
Agricultural
Health
Survey
(
AHS)
Applicator
questionnaire
and
is
not
on
the
current
National
Health
and
Nutrition
Examination
Survey
(
NHANES)
list.

6.0
Exposure
Characterization/
Assessment
6.1
Dietary
Exposure/
Risk
Pathway
6.1.1
Residue
Profile
Reference:
Tau­
Fluvalinate.
RED
­
Reregistration
Eligibility
Decision
Document.
Residue
Chemistry
Considerations.
Case
No.
2295;
D300204;
J.
Morales;
02/
22/
05
A
tolerance
is
established
at
40
CFR
§
180.427
(
a)
under
the
name
"
Fluvalinate"
for
"
residues
of
(
alpha
RS
,
2R)­
fluvalinate
[(
RS)­
alpha­
cyano­
3­
phenoxybenzyl
(
R)­
2­[
2­
chloro­
4­
(
trifluoromethyl)
anilino]­
3­
methylbutanoate"
in/
on
honey
at
0.05
ppm.
"
Fluvalinate"
is
the
common
name
for
the
racemic
mixture
of
the
4
isomers
of
cyano­(
3­
phenoxyphenyl)
methyl
N­[
2­
Page
36
of
59
chloro­
4­(
trifluoromethyl)
phenyl]­
valinate
(
CAS
name).
"
Tau­
fluvalinate"
is
the
term
for
the
half
resolved
mixture
(
2
of
the
4
isomers).
The
tolerance
expression
should
be
revised
to
reflect
the
correct
common
name
and
the
CAS
name
as
follows:
"
Tolerances
are
established
for
residues
of
the
insecticide
tau­
fluvalinate
[
cyano­(
3­
phenoxyphenyl)
methyl
N­[
2­
chloro­
4­
(
trifluoromethyl)
phenyl]­
D­
valinate]
...".

The
nature
of
the
residue
in
honey
is
adequately
understood.
Currently
tolerances
are
expressed
in
terms
of
tau­
fluvalinate,
per
se.
The
current
tolerance
expression
is
adequate.
Adequate
data
are
available
to
reassess
the
established
tolerance
for
honey
at
the
same
level.
However,
based
on
the
available
data,
the
established
tolerance
may
be
reduced
from
0.05
ppm
to
0.02
ppm.

A
GC/
ECD
method
is
available
for
the
enforcement
of
tolerances
for
residues
of
tau­
fluvalinate
in
honey;
this
method
has
been
forwarded
to
FDA
for
publication
in
PAM
Vol.
II.
This
method
has
a
limit
of
detection
of
0.01
ppm.

Acceptable
methods
are
available
for
enforcement
and
data
collection
purposes
for
both
plant
and
animal
commodities.
The
Pesticide
Analytical
Manual
(
PAM)
Volume
II
lists
Method
I,
a
GC
method
with
electron
capture
detection
(
ECD),
for
the
enforcement
of
tolerances
for
tau­
fluvalinate
residues
of
concern
in/
on
plant
and
animal
commodities.
The
stated
limits
of
quantitation
are
0.01
ppm
for
plant
commodities
(
except
oil)
and
animal
commodities,
and
0.02
ppm
for
oil.
These
methods
are
not
currently
required
to
support
reregistration
of
tau­
fluvalinate,
as
there
are
no
registered
uses
on
any
plant
or
animal
commodities.

The
FDA
PESTDATA
database
dated
11/
01
(
PAM
Volume
I,
Appendix
I)
indicates
that
taufluvalinate
is
completely
recovered
(
average
recovery
>
80%)
using
multiresidue
methods
Sections
302
(
Luke
method;
Protocol
D)
and
303
(
Mills,
Onley,
Gaither
method;
Protocol
E,
nonfatty).
Recovery
using
Section
304
(
Mills
Method;
Protocol
F,
fatty
food)
was
variable
(
47­
96%).

The
reregistration
requirements
for
magnitude
of
the
residue
in/
on
honey
have
been
satisfied.
Residues
of
tau­
fluvalinate
were
below
the
limit
of
detection
(<
0.01
ppm)
in
all
samples
of
honey
from
the
brood
and
super
layers,
except
one,
taken
0,
28,
42,
and
70
days
following
placement
of
10%
Impr
strips
in
beehives;
the
strips
were
removed
after
42
days,
and
the
honey
supers
were
not
removed
during
treatment.
One
honey
sample
from
the
brood
layer
bore
detectable
residues
at
0.015
ppm.
Residues
were
also
found
to
be
<
0.01
ppm
in
honey
from
hives
treated
at
exaggerated
rates
(
2­
4x)
with
longer
exposure
times.

The
above
data
actually
represent
an
exaggerated
rate
since
honey
supers
remained
in
place
during
treatment
(
current
registration
specifies
that
honey
supers
be
removed
during
treatment);
however,
these
were
the
data
used
to
establish
the
current
honey
tolerance.

All
previously
registered
uses
of
tau­
fluvalinate
(
or
tau­
fluvalinate)
on
food/
feed
crops
have
been
canceled.
Page
37
of
59
6.1.2
Acute
and
Chronic
Dietary
Exposure
and
Risk
Reference:
Tau­
fluvalinate
Acute
and
Chronic
Dietary
Exposure
Assessments
for
the
Reregistration
Eligibility
Decision;
S.
Stanton;
03/
11/
2005;
DP
Barcode
D300203.

Acute
and
chronic
dietary
risk
assessments
were
conducted
using
the
Dietary
Exposure
Evaluation
Model
(
DEEM­
FCID
 
)
,
Version
2.00/
2.02,
and
the
Lifeline
Model
Version
2.0,
which
use
food
consumption
data
from
the
USDA's
Continuing
Surveys
of
Food
Intakes
by
Individuals
(
CSFII)
from
1994­
1996
and
1998.

Acute
Dietary
Exposure
Results
and
Characterization
The
Tier
1
acute
analysis
assumed
100%
crop
treated
and
reassessed
tolerance­
level
residues
of
0.02
ppm
in
honey.
Drinking
water
was
incorporated
directly
in
the
dietary
assessment
using
the
1
in
10
year
annual
peak
concentration
for
surface
water
generated
by
the
PRZM­
EXAMS
model
(
See
Section
6.2,
"
Water
Exposure/
Risk
Pathway"
for
information
on
the
drinking
water
estimates
used
in
the
analysis).

The
resulting
acute
dietary
exposure
estimates
using
the
DEEM­
FCID
model
were
less
than
6%
of
the
aPAD
for
the
U.
S.
population
and
all
population
subgroups.
Tau­
fluvalinate
acute
dietary
exposure
(
food
+
water)
at
the
95th
percentile
was
estimated
at
0.000069
mg/
kg/
day
for
the
U.
S.
population
(
1.4%
of
the
aPAD)
and
0.000257
mg/
kg/
day
(
5.1%
of
the
aPAD)
for
the
most
highly
exposed
population
subgroup
(
All
Infants).
Estimated
acute
exposures
at
the
95th
percentile
using
the
Lifeline
model
were
consistent
with
the
DEEM­
FCID
results
(
1.2%
of
the
aPAD
for
the
U.
S.
population
and
3.9%
of
the
aPAD
for
infants).

Nearly
all
of
the
estimated
acute
dietary
exposure
to
tau­
fluvalinate
is
from
drinking
water.
Estimated
acute
dietary
exposure
to
tau­
fluvalinate
from
honey
represents
between
<
0.01%
and
0.06%
(
children,
1­
2
yrs.
old)
of
the
total
estimated
exposure.

Chronic
Dietary
Exposure
Results
and
Characterization
The
Tier
1
chronic
analysis
assumed
100%
crop
treated
and
reassessed
tolerance­
level
residues
of
0.02
ppm
in
honey.
Drinking
water
was
incorporated
directly
in
the
dietary
assessment
using
the
1
in
10
year
annual
mean
concentration
for
surface
water
generated
by
the
PRZM­
EXAMS
model
(
See
Section
6.2,
"
Water
Exposure/
Risk
Pathway"
for
information
on
the
drinking
water
estimates
used
in
the
analysis).

The
resulting
chronic
dietary
exposure
estimates
using
the
DEEM­
FCID
model
were
less
than
1%
of
the
cPAD
for
the
U.
S.
population
and
all
population
subgroups.
Tau­
fluvalinate
chronic
dietary
exposure
(
food
+
water)
was
estimated
at
0.000014
mg/
kg/
day
for
the
U.
S.
population
(
0.3%
of
the
cPAD)
and
0.000045
mg/
kg/
day
(
0.9%
of
the
cPAD)
for
the
most
highly
exposed
population
subgroup
(
All
Infants).
Estimated
chronic
exposures
using
the
Lifeline
model
were
consistent
with
the
DEEM­
FCID
results
(
0.2%
of
the
cPAD
for
the
U.
S.
population
and
0.8%
of
the
cPAD
for
infants).
Page
38
of
59
Nearly
all
of
the
estimated
chronic
dietary
exposure
to
tau­
fluvalinate
is
from
drinking
water.
Estimated
chronic
dietary
exposure
to
tau­
fluvalinate
from
honey
represents
<
0.01%
of
the
total
estimated
exposure
for
the
U.
S.
population
and
all
population
subgroups.

Table
6.1.
Summary
of
Dietary
Exposure
and
Risk
for
Tau­
fluvalinate
Population
Subgroup
Acute
Dietary
(
95th
Percentile)
1
Chronic
Dietary
DEEM­
FCID
 
Lifeline
DEEM­
FCID
 
Lifeline
Dietary
Exposure
(
mg/
kg)
%
aPAD
Dietary
Exposure
(
mg/
kg)
%
aPAD
Dietary
Exposure
(
mg/
kg/
day)
%
cPAD
Dietary
Exposure
(
mg/
kg/
day)
%
cPAD
General
U.
S.
Population
0.000069
1.4
0.000060
1.2
0.000014
<
1
0.000010
<
1
All
Infants
(<
1
year
old)
0.000257
5.1
0.000197
3.9
0.000045
<
1
0.000038
<
1
Children
1­
2
years
old
0.000109
2.2
0.000126
2.5
0.000021
<
1
0.000020
<
1
Children
3­
5
years
old
0.000098
2.0
0.000103
2.0
0.000020
<
1
0.000017
<
1
Children
6­
12
years
old
0.000068
1.4
0.000062
1.2
0.000013
<
1
0.000010
<
1
Youth
13­
19
years
old
0.000056
1.1
0.000046
<
1.0
0.000010
<
1
0.000007
<
1
Adults
20­
49
years
old
0.000064
1.3
0.000051
1.0
0.000013
<
1
0.000008
<
1
Adults
50+
years
old
0.000058
1.2
0.000051
1.0
0.000014
<
1
0.000009
<
1
Females
13­
49
years
old
0.000064
1.3
0.000056
1.1
0.000013
<
1
0.000009
<
1
1Acute
exposure
is
reported
at
the
95th
percentile
since
it
was
a
Tier
1
dietary
assessment.
Estimated
exposures
at
the
99th
and
99.9th
percentiles
were
also
well
below
HED's
level
of
concern,
with
the
highest
estimated
exposure
at
the
99.9th
percentile
(
infants
using
the
DEEM­
FCID
software)
representing
only
13%
of
the
aPAD.

6.2
Water
Exposure/
Risk
Pathway
Reference:
Tier
II
Estimated
Environmental
Concentration
for
the
Use
of
Tau­
Fluvalinate
for
Apiary
Uses,
Carrots
for
Seed
(
24­
C
SLNs),
Building
Perimeters,
Nurseries,
Ornamentals,
Indoor
Landscapes
and
Honey
for
the
Human
Health
Drinking
Water
Risk
Assessment;
Mark
Corbin;
D304067;
02/
03/
2005.

Tau­
fluvalinate
is
highly
immobile
(
K
d
values
between
853
and
1,708
with
corresponding
K
oc
values
between
110,000
and
370,000,
respectively)
and
practically
insoluble
in
water
(
2.4
ppb
at
25C),
indicating
a
low
potential
for
significant
residues
in
drinking
water.
Nevertheless,
tau­
Page
39
of
59
fluvalinate
is
registered
for
outdoor,
non­
food
uses
(
including
carrots
and
Brassica/
cole
crops
grown
for
seed,
ornamentals
and
building
perimeters)
that
could
potentially
result
in
residues
in
surface
or
ground
water.

The
estimated
drinking
water
concentrations
from
surface
water
sources
were
calculated
using
PRZM
(
Pesticide
Root
Zone
Model)
and
EXAMS
(
Exposure
Analysis
Modeling
System).
Based
on
the
modeling
results,
the
1
in
10
year
annual
mean
(
chronic,
non­
cancer)
concentration
in
surface
water
is
estimated
to
be
0.65
ppb.
The
1
in
10
year
annual
peak
(
acute)
concentration
is
estimated
to
be
1.31
ppb.
The
estimated
ground
water
concentrations
were
calculated
using
the
Tier
I
SCI­
GROW
(
Screening
Concentration
In
Ground
Water)
model.
The
estimated
acute
and
chronic
drinking
water
concentration
from
ground
water
sources
is
0.0025
ppb.
The
higher
PRZM­
EXAMS
estimated
drinking
water
concentrations
for
surface
water
were
used
for
the
acute
and
chronic
dietary
analyses.
The
modeling
results
are
summarized
below:

Table
6.2.
Summary
of
Estimated
Surface
and
Ground
Water
Concentrations
for
Taufluvalinate

Exposure
Duration
Tau­
fluvalinate
Surface
Water
Conc.,
ppb
a
Ground
Water
Conc.,
ppb
b
Acute
1.31
0.0025
Chronic
(
non­
cancer)
0.65
0.0025
a
From
the
Tier
II
PRZM­
EXAMS
­
Index
Reservoir
model.
Input
parameters
are
based
on
multiple
(
12)
applications
to
woody
ornamentals
in
Oregon
at
the
maximum
application
rate
of
0.34
lb.
a.
i./
A,
the
upper
90th
percentile
aerobic
soil
metabolic
half­
life
of
22.2
days,
a
photolysis
half­
life
of
1
day
and
the
average
K
oc
value
of
244,000.
b
From
the
SCI­
GROW
model
assuming
12
applications
to
woody
ornamentals
at
the
maximum
use
rate
of
0.34
lb.
ai/
A,
the
median
K
oc
of
270,000,
and
the
average
aerobic
soil
metabolic
halflife
of
11.5
days.

6.3
Residential
(
Non­
Occupational)
Exposure/
Risk
Pathway
Although
tau­
fluvalinate
is
labeled
for
use
in
residential
areas,
a
residential
exposure
assessment
was
not
conducted,
since
there
is
little
potential
for
exposure
from
these
uses.
Tau­
fluvalinate
may
be
applied
in
residential
areas
to
building
surfaces/
perimeters
and
ant
mounds
by
commercial
applicators
only
(
i.
e.,
no
homeowner
applications
are
permitted).

°
Building
surfaces
and
perimeters:
Perimeter
applications
are
made
to
a
band
of
soil
and/
or
vegetation
6
to
10
feet
wide
around
and
adjacent
to
the
structure.
Sites
may
include
vegetation
areas,
soil,
trunks
of
woody
ornamentals
and
fence
lines
adjacent
to
or
around
the
structure.
Surface
applications
are
made
as
crack
and
crevice
treatments
to
structures
such
as
porches,
window
and
door
frames,
eaves
and
foundations.

°
Ant
mounds:
Tau­
fluvalinate
is
applied
as
a
drench
to
individual
ant
mounds.
Page
40
of
59
Page
41
of
59
6.3.1
Residential
Handler
Exposure/
Risk
A
residential
handler
exposure
assessment
was
not
conducted,
since
there
are
no
homeowner
uses
of
tau­
fluvalinate
and,
therefore,
no
potential
for
such
exposure.
All
applications
in
residential
areas
are
made
by
commercial
applicators.

6.3.2
Residential
Post­
Application
Exposure/
Risk
The
residential
uses
of
tau­
fluvalinate
are
largely
spot
applications.
There
are
no
wide
area
treatments,
such
as
broadcast
applications
on
home
lawns,
that
would
result
in
significant
postapplication
exposure
of
adults
or
children.
Therefore,
a
residential
post­
application
exposure
assessment
is
not
required.

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
the
ground
application
method
employed
for
tau­
fluvalinate.
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.

7.0
Aggregate
Risk
Assessments
and
Risk
Characterization
In
accordance
with
the
FQPA,
HED
must
consider
and
aggregate
(
add)
pesticide
exposures
and
risks
from
three
major
sources:
food,
drinking
water,
and
residential
exposures.
In
an
aggregate
assessment,
exposures
from
relevant
sources
are
added
together
and
compared
to
quantitative
estimates
of
hazard
(
e.
g.,
a
NOAEL
or
PAD),
or
the
risks
themselves
can
be
aggregated.
When
aggregating
exposures
and
risks
from
various
sources,
HED
considers
both
the
route
and
duration
of
exposure.

For
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
(
EDWCs).
In
order
to
determine
if
aggregate
risks
are
of
concern,
HED
has
historically
calculated
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
were
then
compared
to
the
EDWCs
provided
by
EFED
to
determine
if
a
potential
concern
existed
for
dietary
exposure
to
residues
in
drinking
water.
Page
42
of
59
In
order
to
fully
implement
the
requirements
of
FQPA,
HED
and
EFED
have
been
working
toward
refining
the
screening­
level
DWLOC
approach
to
conducting
aggregate
risk
assessments
that
combine
exposures
across
all
pathways.
As
part
of
this
process,
EFED
and
HED
have
agreed
that
EDWCs
can
be
used
directly
in
dietary
exposure
assessments
to
calculate
aggregate
dietary
(
food
+
water)
risk.
This
is
done
by
using
the
relevant
model
value
as
a
residue
for
drinking
water
(
all
sources)
in
the
dietary
exposure
assessment.
The
principal
advantage
of
this
approach
is
that
the
actual
individual
body
weight
and
water
consumption
data
from
the
CSFII
are
used,
rather
than
assumed
weights
and
consumption
for
broad
age
groups.
This
refinement
has
been
used
in
estimating
the
dietary
exposure
component
in
the
tau­
fluvalinate
aggregate
risk
assessments.

7.1
Acute
Aggregate
Risk
The
acute
aggregate
risk
assessment
considered
exposures
from
food
and
water
only,
because
there
are
no
residential
uses
expected
to
contribute
to
acute
exposures
for
this
chemical.
Since
water
exposure
was
incorporated
directly
into
the
DEEM­
FCID
and
Lifeline
dietary
exposure
analyses,
the
acute
dietary
risk
estimates
reported
in
section
6.1.2
represent
the
total
acute
aggregate
risk
for
tau­
fluvalinate.
The
acute
aggregate
risk
estimates
for
the
U.
S.
population
and
all
subgroups
are
<
6%
of
the
aPAD
and,
therefore,
below
HED's
level
of
concern.

7.2
Short­
Term
Aggregate
Risk
There
are
no
residential
uses
expected
to
contribute
to
short­
term
exposures
for
this
chemical,
based
on
its
current
use
patterns.
Therefore,
a
short­
term
aggregate
assessment
is
not
required.

7.3
Intermediate­
Term
Aggregate
Risk
There
are
no
residential
uses
expected
to
contribute
to
intermediate­
term
exposures
for
this
chemical,
based
on
its
current
use
patterns.
Therefore,
an
intermediate­
term
aggregate
assessment
is
not
required.

7.4
Long­
Term
Aggregate
Risk
The
long­
term
(
chronic)
aggregate
risk
assessment
considered
exposures
from
food
and
water
only,
because
there
are
no
residential
uses
expected
to
contribute
to
chronic
exposures
for
this
chemical.
Since
water
exposure
was
incorporated
directly
into
the
DEEM­
FCID
and
Lifeline
dietary
exposure
analyses,
the
chronic
dietary
risk
estimates
reported
in
section
6.1.2
represent
the
total
chronic
aggregate
risk
for
tau­
fluvalinate.
The
chronic
aggregate
risk
estimates
for
the
U.
S.
population
and
all
subgroups
are
<
1%
of
the
cPAD
and,
therefore,
below
HED's
level
of
concern.

7.5
Cancer
Risk
A
cancer
aggregate
risk
assessment
is
not
required,
since
there
was
no
evidence
of
carcinogenicity
in
the
toxicology
studies
submitted
for
tau­
fluvalinate.
Page
43
of
59
8.0
Cumulative
Risk
Characterization/
Assessment
Tau­
fluvalinate
is
a
member
of
the
pyrethroid
class
of
pesticides.
Although
all
pyrethroids
alter
nerve
function
by
modifying
the
normal
biochemistry
and
physiology
of
nerve
membrane
sodium
channels,
EPA
is
not
currently
following
a
cumulative
risk
approach
based
on
a
common
mechanism
of
toxicity
for
the
pyrethroids.
Although
all
pyrethroids
interact
with
sodium
channels,
there
are
multiple
types
of
sodium
channels,
and
it
is
currently
unknown
whether
they
have
similar
effects
on
all
channels.
In
addition,
we
do
not
have
a
clear
understanding
of
effects
on
key
downstream
neuronal
function,
e.
g.,
nerve
excitability,
nor
do
we
understand
how
these
key
events
interact
to
produce
their
compound­
specific
patterns
of
neurotoxicity.
There
is
ongoing
research
by
both
the
EPA's
Office
of
Research
and
Development
and
the
pyrethroid
registrants
to
evaluate
the
differential
biochemical
and
physiological
actions
of
pyrethroids
in
mammals.
This
research
is
expected
to
be
completed
by
2007.
When
the
results
of
this
research
are
available,
the
Agency
will
make
a
determination
of
common
mechanism
of
toxicity
as
a
basis
for
assessing
cumulative
risk.
For
information
regarding
EPA's
procedures
for
cumulating
effects
from
substances
found
to
have
a
common
mechanism
of
toxicity,
see
EPA's
website
at
http://
www.
epa.
gov/
pesticides/
cumulative/.

9.0
Occupational
Exposure/
Risk
Pathway
Reference:
Tau­
Fluvalinate.
Occupational
and
Residential
Exposure
Chapter
of
the
Reregistration
Eligibility
Decision
Document
(
RED);
DP
Barcode:
D300202;
R.
Travaglini;
03/
24/
05
9.1
Short/
Intermediate/
Long­
Term
Handler
Risk
Occupational
handlers
may
be
exposed
through
the
following
routes
during
mixing,
loading
and
application
of
tau­
fluvalinate
using
aerial,
groundboom,
high/
low
pressure
handwand
or
fogging
equipment
and
during
flagging
operations
for
spray
applications:

°
Dermal:
Although
dermal
exposure
is
expected,
no
toxicity
endpoint
for
dermal
exposure
to
tau­
fluvalinate
has
been
selected.
Dermal
exposure
to
tau­
fluvalinate
is
expected
to
be
largely
self­
limiting
due
to
the
irritation
that
occurs
on
contact
with
the
pesticide
as
a
result
of
the
characteristic
"
pyrethroid
reaction";
and
HED
believes
the
issue
of
dermal
exposure
can
be
best
addressed
by
labeling
to
avoid
contact
with
skin
and
instructions
to
wash
the
affected
area
immediately
following
contact.
Currently
approved
end­
use
product
labels
include
adequate
precautionary
labeling
and
protective
equipment
requirements
(
long­
sleeved
shirt,
long
pants,
chemical­
resistant
gloves,
shoes
and
socks
and
a
NIOSH­
approved
respirator)
to
mitigate
risk
from
dermal
exposure.
Therefore,
a
full
dermal
exposure
assessment
was
not
conducted.
However,
a
screening
level
assessment
was
conducted,
based
on
the
systemic
NOAEL
of
100
mg/
kg/
day
from
the
21/
28­
day
dermal
toxicity
study
in
rabbits.
In
this
study,
minimal
irritation
effects
were
seen
at
the
100
mg/
kg/
day
dose
with
indications
of
the
"
pyrethroid
reaction"
only
at
the
higher
doses
(
500
and
2000
mg/
kg/
day).
Margins
of
Exposure
(
MOEs)
based
on
this
endpoint
exceeded
100
for
all
handler
scenarios
at
the
baseline
level
of
protection
(
long­
Page
44
of
59
sleeved
shirts
and
long
pants,
but
no
gloves
or
respirator)
and
are,
therefore,
not
of
concern.

°
Inhalation:
Even
though
the
volatility
of
this
chemical
is
low,
both
short­
and
intermediate­
term
inhalation
exposure
may
occur
based
on
the
use
patterns
for
taufluvalinate
Long­
term
inhalation
exposure
is
not
anticipated.
An
endpoint
for
short­
and
intermediate­
term
inhalation
exposure
has
been
selected,
based
on
the
NOAEL
of
0.5
mg/
kg/
day
from
the
rat
chronic
feeding
study.
Excessive
salivation
and
lacrimation,
pawing
of
the
bottom
and
sides
of
the
cage,
abnormal
stance,
ruffling,
and
transient
hyperactivity
followed
by
hypoactivity
were
seen
at
the
LOAEL
of
1.0
mg/
kg/
day
in
this
study.

Tau­
fluvalinate
Handler
Exposure
Scenarios:
Pesticide
handlers
may
be
exposed
to
taufluvalinate
in
a
variety
of
occupational
settings
based
on
its
currently
registered
use
patterns.
These
use
patterns
are
summarized
below,
along
with
assumptions
regarding
the
daily
area
or
acreage
treated
by
handlers:

Table
9.1a
Summary
of
Tau­
fluvalinate
Use
Patterns
Crop
or
Treated
Area
Max.
Application
Rate
(
lbs
ai/
acre;
lbs./
gallon)
Application
Method
Application
Formulation
Daily
Area
or
Acreage
Treated1
bee
hives
10.25
%
a.
i./
strip
placement
impregnated
5
combs
carrots/
brassica
0.15
aerial/
ground­
boom
liquid
350/
80
acres
outdoor/
indoor
ornamentals
0.0016
lbs
ai/
gal.
low
pressure
handwand
liquid
40
gal./
day
outdoor
perimeter
treatments
(
structures,
buildings,
etc)
0.0016
lbs
ai/
gal
high
pressure
handwand
liquid
1000
gal./
day
greenhouses
0.0016
lbs
ai/
gal
high
pressure
handwand
liquid
1000
gal./
day
greenhouse
fog
treatment
0.0016
lbs
ai/
gal
fogger
liquid
1000
gal./
day
cut
flowers/
cuttings
0.0008
dip
liquid
1000
gal./
day
ant
mounds
0.0016
lbs
ai/
gal
low
pressure
handwand
liquid
40
gal./
day
1
The
daily
areas
treated
were
defined
for
each
handler
scenario
(
in
appropriate
units)
by
determining
the
amount
that
can
be
reasonably
treated
in
a
single
day
(
e.
g.,
acres,
#
or
combs
or
gallons
per
day).
When
possible,
the
assumptions
for
daily
areas
treated
were
taken
from
the
Health
Effects
Division
Science
Advisory
Committee
on
Exposure
SOP
#
9:
Standard
Values
for
Daily
Acres
Treated
in
Agriculture,
completed
on
July
5,
2000.
Page
45
of
59
HED
evaluated
occupational
inhalation
exposures
for
uses
on
carrots/
brassica,
outdoor/
indoor
ornamentals,
outdoor
perimeter
treatments
(
structures,
buildings,
etc),
greenhouses
and
ant
mounds.
HED
did
not
evaluate
the
remaining
uses
(
beehives,
greenhouse
fog
treatment
and
cut
flowers/
cuttings),
as
explained
below:

°
In
the
case
of
the
treated
strips
used
in
beehives,
an
outdoor
use,
HED
believes
that
exposure
to
the
tau­
fluvalinate
impregnated
in
the
strips
will
be
minimal
due
to
its
low
vapor
pressure
(
10
­
7
Torr).

°
In
the
case
of
cut
flowers/
cuttings,
HED
feels
that
the
high
pressure
handwand
greenhouse
scenario
would
be
a
comparable,
protective
estimate
of
exposure
to
tau­
fluvalinate
through
this
use.

°
In
the
case
of
greenhouse
fog
treatments,
HED
does
not
have
data
with
which
to
estimate
possible
tau­
fluvalinate
exposures
through
this
use.
To
address
these
potential
exposures,
HED
is
requiring
the
registrant
to
submit
occupational
exposure
data
for
greenhouse
exposure
scenarios
(
OPPTS
Guideline
875.2500).

HED
identified
8
specific
occupational
handler
exposure
scenarios
for
the
selected
uses
and
evaluated
each
of
these
for
short­
and
intermediate­
term
inhalation
exposures
to
tau­
fluvalinate:

13.
Mix/
load:
Liquids
to
Support
Aerial
Application
on
carrots/
brassica,
14.
Application:
Aerial
Spray
Application
on
carrots/
brassica,
15.
Application:
Groundboom
Spray
Application
on
carrots/
brassica,
16.
Flagger:
To
Support
Aerial
Application
on
carrots/
brassica,
17.
Mix/
load/
application
on
non­
agricultural
outdoor
areas,
structures,
buildings
etc.
(
high
pressure
handwand),
18.
Mix/
load/
application
for
greenhouses
(
high
pressure
handwand),
19.
Mix/
load/
application
for
outdoor
ornamentals
(
low
pressure
handwand),
and
20.
Mix/
load/
application
for
ant
mounds
(
low
pressure
handwand).

Data
and
Assumptions
For
Handler
Exposure
Scenarios:

Because
no
chemical
specific
data
and/
or
studies
were
submitted
for
this
chemical,
PHED
V1.1
has
been
used
to
assess
the
exposure
scenarios
for
tau­
fluvalinate.
PHED
was
designed
by
a
Task
Force
of
representatives
from
the
U.
S.
EPA,
Health
Canada,
the
California
Department
of
Pesticide
Regulation
and
member
companies
of
the
Crop
Life
America
(
formerly
the
American
Crop
Protection
Association).
PHED
is
a
software
system
consisting
of
two
parts
­­
a
database
of
measured
exposure
values
for
workers
involved
in
the
handling
of
pesticides
under
actual
field
conditions
and
a
set
of
computer
algorithms
used
to
subset
and
statistically
summarize
the
selected
data.
Currently,
the
database
contains
values
for
over
1,700
monitored
individuals
(
i.
e.,
replicates).

The
assumptions
used
in
calculating
handler
exposures
and
risks
are
listed
below:
Page
46
of
59

Application
Rates:
The
application
rates
are
the
maximum
allowable
rates
that
were
identified
on
the
registered
product
labels
for
each
use
assessed
in
this
document.

Acreage
Treated:
The
daily
acres
treated
are
HED
standard
values
(
Health
Effects
Division
Science
Advisory
Committee
on
Exposure
SOP
#
9:
Standard
Values
for
Daily
Acres
Treated
in
Agriculture,
completed
on
July
5,
2000).

Unit
Exposures:
The
unit
exposure
values
calculated
by
PHED
generally
range
from
the
geometric
mean
to
the
median
of
the
selected
data
set.
To
add
consistency
and
quality
control
to
the
values
produced
from
this
system,
the
PHED
Task
Force
has
evaluated
all
data
within
the
system
and
has
developed
a
set
of
grading
criteria
to
characterize
the
quality
of
the
original
study
data.
The
assessment
of
data
quality
is
based
on
the
number
of
observations
and
the
available
quality
control
data.
While
data
from
PHED
provides
the
best
available
information
on
handler
exposures,
it
should
be
noted
that
some
aspects
of
the
included
studies
(
e.
g.,
duration,
acres
treated,
pounds
of
active
ingredient
handled)
may
not
accurately
represent
labeled
uses
in
all
cases.

Amount
Handled:
Based
on
the
daily
acres
treated.

Personal
Protective
Equipment
(
PPE):
HED
calculated
Margins
of
Exposure
(
MOEs)
for
the
baseline,
minimum
PPE,
PPE1,
PPE2
and
engineering
controls
for
each
occupational
exposure
scenario
under
the
following
assumptions:

All
Scenarios:
All
occupational
handlers
are
wearing
footwear
(
socks
plus
shoes
or
boots).
Footwear
is
assumed
to
provide
100
percent
exposure
protection.

Baseline
Attire:
All
handlers
are
wearing
long­
sleeved
shirts
and
long
pants,
but
no
gloves
or
respirator.

Minimum
PPE
(
PPE
1):
All
handlers
are
wearing
long­
sleeved
shirts,
long
pants
and
gloves,
but
no
respirator.

PPE
2:
All
handlers
are
wearing
long­
sleeved
shirts,
long
pants,
gloves
and
a
PF5
respirator
(
dust/
mist
respirator
with
a
protection
factor
of
5).
Note:
Current
labels
require
this
level
of
protection.

Engineering
Controls:
Indicates
the
use
of
an
appropriate
engineering
control
such
as
a
closed
tractor
cab
or
closed
loading
system
for
granulars
or
liquids.

Occupational
Handler
Exposure
and
Risk
Estimates:

Summaries
of
the
short­
and
intermediate­
term
inhalation
risks
at
each
level
of
protection
(
baseline
,
PPE1,
PPE2
and
Engineering
Controls)
are
presented
below
in
Tables
9.1b
through
9.1d.
The
short­
and
intermediate­
term
MOEs
are
the
same
because
the
toxicological
endpoints
for
both
exposure
durations
are
the
same
for
tau­
fluvalinate.
Page
47
of
59
*
Note:
Baseline
Attire
and
Minimum
PPE
(
PPE1)
differ
only
in
the
use
of
gloves,
which
would
not
affect
inhalation
exposure.
Therefore,
the
estimated
inhalation
exposures
and
risks
for
these
levels
of
protection
would
be
the
same
and
are
presented
together
in
Table
9.1b.

Table
9.1b
Short­
and
Intermediate­
Term
Inhalation
Exposures
and
Risks
Assuming
Baseline
PPE
or
PPE1
Exposure
Scenario
(
Scenario
#)
Inhalation
Unit
Exposure
(
Ug/
lb
ai)
1
Crop2
Application
Rate3
Daily
Area
Treated4
Inhalation
Dose
(
mg/
kg/
day)
5
Inhalation
MOE6
Mixer/
Loader
Mixing/
Loading
Liquids
for
Aerial
application
(
1)
1.2
Carrots
&
brassica
crop
group
grown
for
seed
0.15
lb
ai
per
acre
350
Acres
per
day
0.0009
560
Applicator
Sprays
for
Aerial
application
(
2)
Not
Applicable
(
see
engineering
controls)
carrots
&
brassica
crop
group
grown
for
seed
0.15
lb
ai
per
acre
350
Acres
per
day
Not
Applicable
(
see
engineering
controls)
Not
Applicable
(
see
engineering
controls)

Sprays
for
Groundboom
Application
(
3)
0.74
carrots
&
brassica
crop
group
grown
for
seed
0.15
lb
ai
per
acre
80
acres
per
day
0.00013
3900
Flagger
Flagging
for
Sprays
application
(
4)
0.35
Carrots
&
brassica
crop
group
grown
for
seed
0.15
lb
ai
per
acre
350
Acres
per
day
0.00026
1900
Mixer/
Loader/
App
Mixing/
Loading/
Applying
Liquids
for
High­
Pressure
HandWand
application
(
5)
120
nonagricultural
areas;
nonresidential
ind
ustrial
outdoor
areas;
buildings,
structures.
0.0016
lb
ai
per
gallon
1000
Gallons
per
day
0.0027
180
Mixing/
Loading/
Applying
Liquids
for
High­
Pressure
HandWand
application
(
6)
120
greenhouses
0.0016
lb
ai
per
gallon
1000
Gallons
per
day
0.0027
180
Mixing/
Loading/
Applying
Liquids
for
Low
Pressure
Handwand
application
(
7)
30
outdoor
ornamentals
0.0016
lb
ai
per
gallon
40
Gallons
per
day
0.000027
18000
Mixing/
Loading/
Applying
Liquids
for
Low
Pressure
Handwand
application
(
8)
30
ant
mounds
0.0016
lb
ai
per
gallon
40
Gallons
per
day
0.000027
18000
1Baseline
and
PPE1
inhalation
unit
exposures
represent
no
respirator.
Values
are
reported
in
the
PHED
Surrogate
Exposure
Guide
dated
August
1998
or
are
from
data
submitted
by
the
Outdoor
Residential
Exposure
Task
Force
dated
May
2000.
2Crops
and
use
patterns
are
from
product
labeling
&
LUIS
Report.
3Application
rates
are
based
on
maximum
values
found
in
various
sources
including
LUIS
and
various
labels.
In
most
scenarios,
a
range
of
maximum
application
rates
is
used
to
represent
the
range
of
rates
for
different
crops/
sites/
uses.
Most
application
rates
upon
which
the
analysis
is
based
are
Page
48
of
59
presented
as
lb
ai/
A.
In
some
cases,
the
application
rate
is
based
on
applying
a
solution
at
concentrations
specified
by
the
label
(
i.
e.,
presented
as
lb
ai/
gallon).
4Amount
treated
is
based
on
the
area
or
gallons
that
can
be
reasonably
applied
in
a
single
day
for
each
exposure
scenario
of
concern
based
on
the
application
method
and
formulation/
packaging
type.
(
Standard
EPA/
OPP/
HED
values).
5
Inhalation
dose
(
mg/
kg/
day)
=
[
unit
exposure
(
ug/
lb
ai)
*
0.001
mg/
ug
unit
conversion
*
Inhalation
absorption
(
100%)
*
Application
rate
(
lb
ai/
acre
or
lb
ai/
gallon)
*
Daily
area
treated
(
acres
or
gallons)]
/
Body
weight
(
70
kg).
6Inhalation
MOE
=
0.5
mg/
kg/
day
(
oral
NOAEL)
/
Daily
Inhalation
Dose.
Target
Inhalation
MOE
is
100.

Table
9.1c
Short­
and
Intermediate­
Term
Inhalation
Exposures
and
Risks
Assuming
PPE2
Exposure
Scenario
(
Scenario
#)
Inhalation
Unit
Exposure
(
Ug/
lb
ai)
1
Crop2
Application
Rate3
Daily
Area
Treated4
Inhalation
Dose
(
mg/
kg/
day)
5
Inhalation
MOE6
Mixer/
Loader
Mixing/
Loading
Liquids
for
Aerial
application
(
1)
0.24
Carrots
&
brassica
crop
group
grown
for
seed
0.15
lb
ai
per
acre
350
Acres
per
day
0.00018
2800
Applicator
Sprays
for
Aerial
application
(
2)
Not
Applicable
(
see
engineering
controls)
carrots
&
brassica
crop
group
grown
for
seed
0.15
lb
ai
per
acre
350
Acres
per
day
Not
Applicable
(
see
engineering
controls)
Not
Applicable
(
see
engineering
controls)

Sprays
for
Groundboom
Application
(
3)
0.15
carrots
&
brassica
crop
group
grown
for
seed
0.15
lb
ai
per
acre
80
Acres
per
day
0.000026
19000
Flagger
Flagging
for
Sprays
application
(
4)
0.07
Carrots
&
brassica
crop
group
grown
for
seed
0.15
lb
ai
per
acre
350
Acres
per
day
0.000053
9500
Mixer/
Loader/
App
Mixing/
Loading/
Applying
Liquids
for
High­
Pressure
HandWand
application
(
5)
24
nonagricultural
areas;
nonresidential
ind
ustrial
outdoor
areas;
buildings,
structures.
0.0016
lb
ai
per
gallon
1000
Gallons
per
day
0.00055
910
Mixing/
Loading/
Applying
Liquids
for
High­
Pressure
HandWand
application
(
6)
24
greenhouses
0.0016
lb
ai
per
gallon
1000
Gallons
per
day
0.00055
910
Mixing/
Loading/
Applying
Liquids
for
Low
Pressure
Handwand
application
(
7)
6
outdoor
ornamentals
0.0016
lb
ai
per
gallon
40
Gallons
per
day
0.0000055
91000
Mixing/
Loading/
Applying
Liquids
for
Low
Pressure
Handwand
application
(
8)
6
ant
mounds
0.0016
lb
ai
per
gallon
40
Gallons
per
day
0.0000055
91000
1PPE2
inhalation
unit
exposures
represent
a
dust/
mist
respirator
with
a
protection
factor
of
5.
Values
are
reported
in
the
PHED
Surrogate
Exposure
Guide
dated
August
1998
or
are
from
data
submitted
by
the
Outdoor
Residential
Exposure
Task
Force
dated
May
2000.
2Crops
and
use
patterns
are
from
product
labeling
&
LUIS
Report.
Page
49
of
59
3Application
rates
are
based
on
maximum
values
found
in
various
sources
including
LUIS
and
various
labels.
In
most
scenarios,
a
range
of
maximum
application
rates
is
used
to
represent
the
range
of
rates
for
different
crops/
sites/
uses.
Most
application
rates
upon
which
the
analysis
is
based
are
presented
as
lb
ai/
A.
In
some
cases,
the
application
rate
is
based
on
applying
a
solution
at
concentrations
specified
by
the
label
(
i.
e.,
presented
as
lb
ai/
gallon).
4Amount
treated
is
based
on
the
area
or
gallons
that
can
be
reasonably
applied
in
a
single
day
for
each
exposure
scenario
of
concern
based
on
the
application
method
and
formulation/
packaging
type.
(
Standard
EPA/
OPP/
HED
values).
5
Inhalation
dose
(
mg/
kg/
day)
=
[
unit
exposure
(
ug/
lb
ai)
*
0.001
mg/
ug
unit
conversion
*
Inhalation
absorption
(
100%)
*
Application
rate
(
lb
ai/
acre
or
lb
ai/
gallon)
*
Daily
area
treated
(
acres
or
gallons)]
/
Body
weight
(
70
kg).
6Inhalation
MOE
=
0.5
mg/
kg/
day
(
oral
NOAEL)
/
Daily
Inhalation
Dose.
Target
Inhalation
MOE
is
100.

Table
9.1d
Short­
and
Intermediate­
Term
Inhalation
Exposures
and
Risks
Assuming
Use
of
Engineering
Controls
Exposure
Scenario
(
Scenario
#)
Inhalation
Unit
Exposure
(
Ug/
lb
ai)
1
Crop2
Application
Rate3
Daily
Area
Treated4
Inhalation
Dose
(
mg/
kg/
day)
5
Inhalation
MOE6
Mixer/
Loader
Mixing/
Loading
Liquids
for
Aerial
application
(
1)
0.083
carrots
&
brassica
crop
group
grown
for
seed
0.15
lb
ai
per
acre
350
Acres
per
day
0.000062
8000
Applicator
Sprays
for
Aerial
application
(
2)
0.068
carrots
&
brassica
crop
group
grown
for
seed
0.15
lb
ai
per
acre
350
Acres
per
day
0.000051
9800
Sprays
for
Groundboom
Application
(
3)
0.43
carrots
&
brassica
crop
group
grown
for
seed
0.15
lb
ai
per
acre
80
Acres
per
day
0.0000074
68000
Flagger
Flagging
for
Sprays
application
(
4)
0.07
carrots
&
brassica
crop
group
grown
for
seed
0.15
lb
ai
per
acre
350
Acres
per
day
0.0000053
95000
Mixer/
Loader/
App
Mixing/
Loading/
Applying
Liquids
for
High­
Pressure
HandWand
(
5)
Not
Applicable
(
NA)
nonagricultural
areas;
nonresidential
ind
ustrial
outdoor
areas;
buildings,
structures
0.0016
lb
ai
per
gallon
1000
Gallons
per
day
Data
not
available
Data
not
available
Mixing/
Loading/
Applying
Liquids
for
High­
Pressure
HandWand
application
(
6)
NA
greenhouses
0.0016
lb
ai
per
gallon
1000
Gallons
per
day
Data
not
available
Data
not
available
Mixing/
Loading/
Applying
Liquids
for
High­
Pressure
HandWand
application
(
7)
NA
outdoor
ornamentals
0.0016
lb
ai
per
gallon
40
Gallons
per
day
Data
not
available
Data
not
available
Mixing/
Loading/
Applying
Liquids
for
Low
Pressure
Handwand
application
(
8)
NA
ant
mounds
0.0016
lb
ai
per
gallon
40
Gallons
per
day
Data
not
available
Data
not
available
1Engineering
controls
inhalation
unit
exposures
represent
no
respirator.
Values
are
reported
in
the
PHED
Surrogate
Exposure
Guide
dated
August
1998
or
are
from
data
submitted
by
the
Outdoor
Residential
Exposure
Task
Force
dated
May
2000.
2Crops
and
use
patterns
are
from
product
labeling
&
LUIS
Report.
Page
50
of
59
3Application
rates
are
based
on
maximum
values
found
in
various
sources
including
LUIS
and
various
labels.
In
most
scenarios,
a
range
of
maximum
application
rates
is
used
to
represent
the
range
of
rates
for
different
crops/
sites/
uses.
Most
application
rates
upon
which
the
analysis
is
based
are
presented
as
lb
ai/
A.
In
some
cases,
the
application
rate
is
based
on
applying
a
solution
at
concentrations
specified
by
the
label
(
i.
e.,
presented
as
lb
ai/
gallon).
4Amount
treated
is
based
on
the
area
or
gallons
that
can
be
reasonably
applied
in
a
single
day
for
each
exposure
scenario
of
concern
based
on
the
application
method
and
formulation/
packaging
type.
(
Standard
EPA/
OPP/
HED
values).
5
Inhalation
dose
(
mg/
kg/
day)
=
[
unit
exposure
(
ug/
lb
ai)
*
0.001
mg/
g
unit
conversion
*
Inhalation
absorption
(
100%)
*
Application
rate
(
lb
ai/
acre
or
lb
ai/
gallon)
*
Daily
area
treated
(
acres
or
gallons)]
/
Body
weight
(
70
kg).
6Inhalation
MOE
=
0.5
mg/
kg/
day
(
oral
NOAEL)
/
Daily
Inhalation
Dose.
Target
Inhalation
MOE
is
100.

HED
believes
that
the
risk
values
presented
in
this
occupational
assessment
represent
the
best
quality
results
that
could
be
produced
given
the
exposure,
use
and
toxicology
data
that
are
available.
HED
also
believes
that
the
risks
represent
reasonable
worse­
case
estimates
of
handler
exposure,
because
maximum
application
rates
are
coupled
with
medium­
to
high­
end
estimates
of
area
treated
daily
to
define
risk
estimates
that
likely
fall
in
the
upper
percentiles
of
the
actual
exposure
distributions.
Using
these
worst­
case
assumptions,
estimated
occupational
handler
MOEs
for
all
exposure
scenarios
at
all
protection
levels
are
greater
than
100
and
are,
therefore,
not
of
concern.

Estimated
inhalation
exposures
at
the
baseline
and
PPE1
levels
of
protection
are
particularly
conservative,
since
they
assume
respirators
are
not
being
used
by
handlers.
In
fact,
current
labels
require
handlers
to
wear
NIOSH
approved
respirators
(
in
addition
to
long­
sleeved
shirt,
long
pants,
chemical­
resistant
gloves,
shoes
and
socks)
for
both
indoor
and
outdoor
applications.

9.2
Short/
Intermediate/
Long­
Term
Postapplication
Risk
Post­
application
dermal
exposure
to
tau­
fluvalinate
is
expected
to
be
largely
self­
limiting
due
to
the
irritation
that
occurs
on
contact
with
the
pesticide
as
a
result
of
the
characteristic
"
pyrethroid
reaction"
(
see
sec.
9.1).
Therefore,
post­
application
dermal
exposure
and
risk
were
not
assessed.

With
the
exception
of
the
greenhouse
uses,
post­
application
inhalation
exposure
to
tau­
fluvalinate
is
expected
to
be
minimal.
Potential
post­
application
inhalation
exposure
in
greenhouses
is
likely
mitigated
by
the
ventilation
requirements
of
the
Worker
Protection
Standard
(
WPS).
For
these
reasons,
a
post­
application
inhalation
exposure
assessment
was
not
deemed
necessary
for
taufluvalinate
However,
to
confirm
that
the
established
re­
entry
interval
(
REI)
of
12
hours
is
adequate,
HED
is
requiring
the
registrant
to
conduct
an
inhalation
post­
application
exposure
study
(
OPPTS
Guideline
875.2500).
The
study
should
be
conducted
in
exact
accordance
with
the
use
directions
on
the
product
label,
including
ventilation
criteria.
The
study
should
be
designed
in
such
a
way
that
it
will
be
of
sufficient
duration
for
the
pesticidal
residue
levels
to
dissipate
to
zero
(
0)
or
to
the
level
of
detection
in
two
separate,
distinct
parts
of
the
treated
area.
The
registrant
should
submit
a
study
protocol
developed
under
the
aforementioned
guidelines
for
Agency
review
prior
to
conducting
the
study.

10.0
Data
Needs
and
Label
Requirements
10.1
Toxicology
Page
51
of
59

90­
Day
Inhalation
Study
(
OPPTS
Guideline
870.3465)
­
This
study
requirement
is
reserved
pending
outcome
of
the
airborne
residue
dissipation
study
for
greenhouses
(
see
below).

10.2
Residue
Chemistry
­
None
10.3
Occupational
and
Residential
Exposure

Post­
application
occupational
exposure
data
for
greenhouse
exposure
scenarios
(
OPPTS
Guideline
875.2500)

References:

Tau­
Fluvalinate.
RED
­
Reregistration
Eligibility
Decision
Document.
Residue
Chemistry
Considerations.
Case
No.
2295;
D300204;
J.
Morales;
02/
22/
05
Tau­
Fluvalinate
RED
­
Reregistration
Eligibility
Decision.
Product
Chemistry
Considerations.
Case
No.
2295;
D311824;
J.
Morales;
02/
22/
05
Tau­
fluvalinate
Acute
and
Chronic
Dietary
Exposure
Assessments
for
the
Reregistration
Eligibility
Decision;
D300203;
S.
Stanton;
03/
11/
05
Tier
II
Estimated
Environmental
Concentration
for
the
Use
of
Tau­
Fluvalinate
for
Apiary
Uses,
Carrots
for
Seed
(
24­
C
SLNs),
Building
Perimeters,
Nurseries,
Ornamentals,
Indoor
Landscapes
and
Honey
for
the
Human
Health
Drinking
Water
Risk
Assessment;
D304067;
Mark
Corbin;
02/
03/
2005
Revised,
Corrected
Tau­
Fluvalinate.
Occupational
and
Residential
Exposure
Chapter
of
the
Reregistration
Eligibility
Decision
Document
(
RED);
D319595;
R.
Travaglini;
06/
26/
05
Review
of
Fluvalinate
Incident
Reports,
D300199,
Jerome
Blondell,
03/
14/
2005
Page
52
of
59
Appendices
1.0
TOXICOLOGY
DATA
REQUIREMENTS
The
toxicology
data
requirements
(
40
CFR
158.340)
for
tau­
fluvalinate
are
in
Table
1.
Use
of
the
new
guideline
numbers
does
not
imply
that
the
new
(
1998)
guideline
protocols
were
used.

Test
Technical
Required
Satisfied
870.1100
Acute
Oral
Toxicity
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.1200
Acute
Dermal
Toxicity
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.1300
Acute
Inhalation
Toxicity
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.2400
Primary
Eye
Irritation
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.2500
Primary
Dermal
Irritation
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.2600
Dermal
Sensitization
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
yes
yes
no
yes
yes
yes
yes
yes
no
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
yes
no
reserved
(
2)
yes
yes
(
1)
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
yes
yes
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
Acute
Delayed
Neurotox.
(
hen)
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.6100b
90­
Day
Neurotoxicity
(
hen)
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.6200a
Acute
Neurotox.
Screening
Battery
(
rat)
.
.
.
.
.
.
.
.
.
870.6200b
90
Day
Neuro.
Screening
Battery
(
rat)
.
.
.
.
.
.
.
.
.
.
.
870.6300
Develop.
Neuro
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
no
no
yes
yes
no
­
­
Partial
(
3)
yes
­­

870.7485
General
Metabolism
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.7600
Dermal
Penetration
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
yes
no
yes
­­

Special
Studies
for
Ocular
Effects
Acute
Oral
(
rat)
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
Subchronic
Oral
(
rat)
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
Six­
month
Oral
(
dog)
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
no
no
no
 
 
­
­

(
1)
­
Satisfied
by
the
chronic
dog
study.
(
2)
­
Reserved
pending
outcome
of
the
greenhouse
fogger/
mist
study
(
i.
e.,
airborne
residue
dissipation
study).
(
3)
­
A
non­
guideline
study
is
available
for
partial
fulfillment
of
this
requirement;
an
additional
study
is
not
required.
Page
53
of
59
2.0
NON­
CRITICAL
TOXICOLOGY
STUDIES
1.
(
82­
1a)
13­
Week
Feeding
Study
in
Rats.
Zoecon
Corporation.
1981.
MRID
No.
00094109,
92069032.
HED
Doc.
No.
002256.

In
a
90­
day
subchronic
feeding
study
in
rats
(
1981,
MRID
00094109),
groups
of
20
male
and
20
female
21
day
old
Charles
River
COBS
CD
rats
were
administered
0.3,
1.0,
3.0,
30.0
or
50.0
mg/
kg
b.
w./
day
tau­
fluvalinate
(
88.2­
93.1.%,
Lot
#
455­
95,
468­
27,
Run
23)
in
the
diet
which
was
adjusted
weekly
for
concentration.

Salivation
and
abnormal
gait
were
observed
in
the
50.0
mg/
kg/
day
group.
Skin
lesions
were
observed
in
males
at
3.0
mg/
kg/
day
and
higher
dose
levels.
Skin
lesions
were
observed
in
females
beginning
at
30.0
mg/
kg/
day.
Body
weights
were
15.8
and
25.3%
less
than
controls
in
males
in
the
30.0
and
50.0
mg/
kg/
day
groups,
respectively.
Body
weights
were
6.3
and
11.9%
less
than
controls
in
females
in
the
30.0
and
50.0
mg/
kg/
day
groups,
respectively.
The
hematocyte,
hemoglobin
levels
and
erythrocyte
counts
were
decreased
at
30.0
and
50.0
mg/
kg/
day.
The
BUN
was
increased
somewhat
in
the
30.0
and
50.0
mg/
kg/
day
groups.
Albumin
and
total
bilirubin
were
decreased
at
30.0
and
50.0
mg/
kg/
day.
On
histological
examination
of
the
tissues,
there
was
significant
damage
to
the
skin
characterized
by
focal
ulceration
and
inflammation
extending
to
the
muscularis.
The
Systemic
LOEL
was
3.0
mg/
kg/
day
based
on
the
occurrence
of
skin
lesions
(
due
to
systemic
neurotoxicity).
The
Systemic
NOEL
was
1.0
mg/
kg/
day.

The
study
is
acceptable
and
satisfies
the
requirement
for
a
guideline
series
82­
1(
a)
90­
day
subchronic
feeding
study
in
rats.

2.
(
82­
1a)
13­
Week
Feeding
Study
in
Mice.
Zoecon
Corporation.
1981.
MRID
No.
00094113.
HED
Doc.
No.
004705.

In
a
13­
week
subchronic
feeding
study
in
mice
(
1981,
MRID
00094113),
groups
of
10
male
and
10
female
41­
day
old
CD­
1
mice
were
administered
0,
1,
3,
30,
50
or
100
mg/
kg
b.
w./
day
of
taufluvalinate
(
89.9­
93.1%,
Anal
10801­
91,
Anal
0281037,
Run
23R)
in
the
diet.
Compound­
related
effects
noted
included
infected
skin
lesions,
related
effects,
and
their
sequelae
(
increased
WBC
counts,
enlarged
lymph
nodes,
infected
eyes,
and
splenic
changes
in
all
dosage
groups).
Male
body
weights
were
significantly
decreased
in
groups
receiving
30
mg/
kg/
day
or
more.
Female
HCT,
HGB,
RBC
and
reticulocytes
were
significantly
decreased
in
the
100
mg/
kg/
day
group.
The
ovaries
in
the
100
mg/
kg/
day
group
were
significantly
decreased
and
had
ovarian
cysts.
Histological
examinations
of
the
ovaries
were
not
performed
in
the
other
groups.
The
NOEL
and
LOEL
were
not
determined.

The
study
is
supplementary
and
does
not
satisfy
the
requirement
for
a
guideline
series
82­
1(
a)
90­
day
subchronic
feeding
study
in
rodents.

3.
(
82­
1a)
14­
Day
Range
Finding
Study
in
Mice.
Zoecon
Corporation.
1981.
MRID
No.
00094105.
HED
Doc
No.
002256.
(
also
racemic
mixture)
Page
54
of
59
In
a
14­
day
rangefinding
toxicity
study
in
mice
(
1981,
MRID
00094105),
groups
of
5
male
and
5
female
CD­
1
mice
were
administered
0,
0.2,
0.7,
2.0,
7.0,
20.0,
70.0.
200.0
or
700.0
(
doses
approximately
0,
0.03,
0.10,
0.30,
1.00,
3.00,
10.00,
30.00
or
100.00
mg/
kg/
day)
of
taufluvalinate
(
89.9%,
#
1080­
91)
in
the
diet.
Another
group
of
5
male
and
5
female
mice
per
group
were
administered
0,
20.0,
70.0,
200.0
or
700.0
ppm
(
doses
approximately
0,
3.0,
10.0,
30.0
or
100.0
mg/
kg/
day)
of
fluvalinate
(
racemic)
(
93.8%,
Anal
0979­
069,
Run
#
7)
in
the
diet.

Tau­
fluvalinate
­
Hair
loss,
local
crusting
and
skin
ulceration
were
note
at
10
(
F)
and
30
mg/
kg/
day
(
M
and
F)
and
above.
Excessive
salivation,
ataxia,
reduced
motor
activity,
skin
paleness
and
death
occurred
at
100
mg/
kg/
day.
Body
weight
was
reduced
at
100
mg/
kg/
day.

Fluvalinate
(
racemic)
­
Hair
loss,
local
crusting
and
skin
ulceration
were
observed
in
females
at
10
mg/
kg/
day
and
in
males
at
100
mg/
kg/
day.

Tau­
fluvalinate
is
more
toxic
on
a
mg/
kg
basis
than
the
racemic
technical.
Females
appear
to
be
more
sensitive
than
males.
Quantitative
differences
in
observations
can
be
attributed
to
compound
potency.
There
do
not
appear
to
be
any
qualitative
differences
between
the
two
mixtures.

The
study
is
supplementary
(
by
design
­
rangefinding)
and
does
not
satisfy
the
requirement
for
a
guideline
series
82­
1(
a)
90­
day
subchronic
feeding
study
in
mice.

4.
(
82­
2)
21­
Day
Dermal
Toxicity
Study
in
Rabbits.
Zoecon
Corporation.
1981.
MRID
No.
00094115.
HED
Doc.
No.
002256
In
a
3­
week
dermal
toxicity
study
(
1981,
MRID
00094115),
groups
of
10
male
and
10
female
young
adult
New
Zealand
White
rabbits
were
administered
0,
100,
500
or
2000
mg/
kg/
day
of
taufluvalinate
(
93.1%,
Lot
23R,
#
0281037,
ZTS­
0029).
The
skin
on
the
backs
of
one­
half
of
the
animals
was
abraded.

A
well
defined
erythema
was
observed
in
all
treated
animals.
A
barely
perceptible
edema
was
noted
in
all
treated
males
and
females.
Skin
sores
were
noted
at
dose
levels
of
100
mg/
kg/
day
and
above.
Males
in
the
2000
mg/
kg/
day
group
had
decreased
body
weights.
Food
consumption
was
decreased
in
males
in
the
500
and
2000
mg/
kg/
day
groups
and
in
females
in
the
2000
mg/
kg/
day
group.
Histological
lesions
including
acanthosis,
hyperkeratosis,
acute
and
chronic
dermal
inflammation
and
epidermal
ulceration
were
observed
in
all
treated
animals.
The
NOEL
is
less
than
100
mg/
kg/
day.
The
LOEL
is
100
mg/
kg/
day
based
on
skin
irritation
(
possibly
a
systemic
neurologic
effect
as
well).
The
systemic
NOEL
is
100
mg/
kg/
day
and
the
LOEL
is
500
mg/
kg/
day
based
on
decreased
food
intake.

The
study
is
acceptable
and
satisfies
the
requirement
for
a
guideline
series
82­
2
21­
day
dermal
study
in
rabbits.

5.
(
83­
3)
Chronic
dosing
study
in
dogs.
Covance
Laboratories
Inc.,
9200
Leesburg
Pike,
Vienna,
VA
22182­
1699.
Covance
6398­
117,
December
17,
1998.
MRID
44743201.
Unpublished.
Page
55
of
59
In
a
chronic
toxicity
study
(
1998,
MRID
44743201),
tau­
fluvalinate
(
88.4%
purity)
was
administered
to
4
beagle
dogs/
sex/
dose
in
capsules
at
dose
levels
of
0,
3,
12,
and
50
mg/
kg/
day
for
52
weeks.

There
was
no
effect
on
mortality
in
either
sex
of
dogs.
Clinical
signs
with
a
possible
relationship
to
test
substance
exposure
included
salivation
in
3/
4
males
and
females
and
a
marked
increase
in
the
frequency
of
emesis
(
observed
in
all
dogs),
mainly
postdose,
in
the
high
dose
male
and
female
groups,
signs
consistent
with
CNS
toxicity.
The
body
weights
of
the
high­
dose
males
were
significantly
reduced
reaching
85%
of
controls
at
week
40;
those
of
the
mid
and
high­
dose
females
were
consistently
less
than
controls
with
effects
biologically
although
not
statistically
significant,
89
and
93%
at
52
weeks,
respectively.
The
overall
body
weight
gains
of
the
high­
dose
males
(
40%
of
controls,
p<
0.05)
and
mid­
and
high­
dose
females
(
47
and
63%,
N.
S.,
respectively)
were
also
reduced
by
exposure
to
Tau­
Fluvalinate
for
52
weeks.
There
were
no
compoundrelated
effects
on
food
consumption,
hematology,
clinical
chemistry,
or
gross
and
histologic
pathology.
Liver
weights,
absolute
and
relative
to
body
and
brain
weight,
were
significantly
increased
by
exposure
to
the
test
compound
in
the
high
dose
male
(
120,
138,
and
121%,
respectively,
all
p<
0.05)
and
females
(
124,
129,
and
127%,
respectively,
p<
0.05
for
relative
body
weight)
and
possibly
in
the
mid­
dose
female
group
(
110,110,
and
104%,
respectively,
all
N.
S.).
The
Tau­
fluvalinate
LOAEL
for
female
dogs
is
12
mg/
kg/
day
based
on
decreased
body
weight
and
body
weight
gain
and
increased
liver
weight.
The
NOAEL
for
female
dogs
is
3
mg/
kg/
day.
The
Tau­
fluvalinate
LOAEL
for
male
dogs
is
50
mg/
kg/
day,
based
on
decreased
body
weight
and
body
weight
gain,
increased
liver
weight,
and
increased
emesis
and
salivation.
The
NOAEL
for
males
is
12
mg/
kg/
day.

This
chronic
study
in
the
dog
is
Acceptable/
Guideline
and
satisfies
the
guideline
requirement
for
a
chronic
oral
study
[
OPPTS
870l4100,
OECD
452]
in
the
dog.

6.
(
83­
5)
2­
Year
Dosing/
Carcinogenicity
Study
in
Mice.
Zoecon
Corporation.
1984.
MRID
No.
00094889,
00128336,
00144628,
92069036.
HED
Doc.
No.
004705.

In
a
24­
month
combined
chronic/
carcinogenicity
study
(
1984,
MRID
00094889,
00128336,
00144628,
92069036),
groups
of
60
49­
day
old
Charles
River
CD­
1
mice
(
except
for
a
second
control
group
containing
50
animals/
sex/
dose)
were
administered
0,
2,
10
or
20
mg/
kg
b.
w./
day
of
tau­
fluvalinate
(
92.1%.
Run
23,
Anal
#
0281028)
in
the
diet
which
was
frequently
adjusted
to
achieve
the
appropriate
concentrations.
Ten
animals/
sex/
dose
were
sacrificed
from
the
2
control
groups
and
the
10
and
20
mg/
kg/
day
groups
at
week
52.

Skin
lesions
were
noted
in
the
10
and
20
mg/
kg/
day
groups.
Chronic
nephritis
was
increased
in
males
in
the
20
mg/
kg/
day
group.
There
was
no
indication
that
tau­
fluvalinate
was
carcinogenic
in
mice.

The
NOEL
is
2
mg/
kg/
day.
The
LOEL
is
10
mg/
kg/
day
based
on
dermal
lesions
(
due
to
systemic
neurotoxicity).
Tau­
fluvalinate
is
not
carcinogenic
in
mice.
Page
56
of
59
The
study
is
acceptable
and
satisfies
the
requirement
for
a
guideline
series
83­
2
carcinogenic
study
in
mice.
The
study
is
supplementary
and
does
not
satisfy
the
requirement
for
a
guideline
series
83­
1
chronic
feeding
study
in
mice.

7.
(
85­
1).
Metabolism
study
in
mice.
Zoecon
Corporation,
Palo
Alto,
CA;
No.
3760­
2­
02­
84;
dated
February
21,
1984.
Accession
No.
072918.
Unpublished.

In
a
metabolism
study
(
1984,
MRID
No.
072918)
[
trifluoromethy­
14C­]
tau­
fluvalinate
and
nonlabeled
tau­
fluvalinate,
were
administered
in
feed
to
male
and
female
mice
(
ICR
strain,
Simonsens
Laboratories,
Gilroy,
CA).
Treatment
groups
consisted
of
3
rats/
sex
given
at
doses
of
approximately
26
mg/
kg/
day
for
six
days.

Tau­
fluvalinate
was
rapidly
absorbed,
metabolized,
distributed
and
excreted
following
oral
administration
and
most
material
was
recovered
in
the
urine
and
feces
in
both
male
and
female
mice
pre­
fed
unlabelled
tau­
fluvalinate
at
approximately
26
mg/
kg/
day.
Approximately
59
percent
and
30
percent
of
the
applied
dose
was
excreted
in
the
feces
and
urine,
respectively,
during
the
4­
day
experiment,
with
most
of
the
radioactivity
eliminated
during
the
first
day.
The
major
products
identified
in
the
urine
included
2­[
2­
chloro­
4­(
trifluoromethyl)
anilino]­
3­
methyl­
butanoic
acid
(
anilino
acid)
and
the
taurine
conjugate
of
the
anilino
acid,
which
accounted
for
8.2­
12.0
and
1.7­
3.2
percent
of
day
1
radioactivity
in
urine,
respectively.
In
addition,
7
urinary
metabolites
were
found
but
not
identified.
Parent
tau­
fluvalinate
represented
15­
23%
of
the
radioactivity
in
the
day
1
fecal
extracts,
and
the
anilino
acid
represented
approximately
11
percent
of
fecal
radioactivity.
In
addition,
five
fecal
metabolites
were
found
but
not
identified.
Little
radioactivity
was
found
in
any
of
the
tissues
or
carcasses
and
no
major
sex
differences
were
observed.
This
metabolism
study
in
the
mice
is
classified
acceptable/
non­
guideline
and
does
not
satisfy
the
guideline
requirement
for
a
metabolism
study
[
OPPTS
870.7485,
OECD
417]
in
mice.
The
limiting
factor
is
the
study
used
only
3
mice/
sex
whereas
the
Guidelines
require
4
mice/
sex.

8.
(
85­
1).
Metabolism
study
in
rats.
Sandoz,
Study
No.
480605­
13,
May
20,
1992.

In
this
study
(
1992,
MRID
No.:
42322301),
a
single
oral
dose
of
14C­
fluvalinate
at
1
mg/
kg
(
Group
A),
200
mg/
kg
(
Group
C),
or
unlabelled
tau­
fluvalinate
at
1
mg/
kg/
day
for
14
days
followed
by
a
single
dose
of
14C­
fluvalinate
at
1
mg/
kg
(
Group
B)
were
administered
to
CD
rats.
The
rats
were
sacrificed
96
hours
later
following.
For
groups
A
and
B,
approximately
75%
of
the
dose
was
detected
in
the
excreta
by
24
hours
after
dosing.
For
the
high
dose
rats
(
Group
C),
however,
elimination
of
the
radioactivity
was
only
45%
of
the
dose
at
24
hours.
By
96
hours
after
administration,
approximately
90%
of
the
dose
in
all
groups
was
eliminated.
Over
the
4­
day
test
period,
fecal
excretion
was
the
dominant
elimination
pathway
accounting
for
approximately
60
to
80%
of
the
administered
tau­
fluvalinate
dose.
The
relative
amounts
of
parent
compound
and
the
major
fecal
metabolite,
anilino
acid
varied
with
dose.
For
groups
A
and
B,
the
parent
compound
and
anilino
acid
represented
about
55
and
10%
respectively,
of
the
fecal
radioactivity.
For
the
high
dose
group
(
200
mg/
kg)
the
parent
compound
and
anilino
acid
represented
about
85%
and
2%
respectively,
of
the
fecal
radioactivity.
Additional
fecal
metabolites,
although
less
significant
were
haloaniline,
3­
phenoxybenzoic
acid,
and
3­(
4"­
hydroxyphenoxy)
benzoic
acid.
With
respect
to
urinary
excretion,
the
low
dose
groups
(
A
and
B),
followed
first
order
kinetics
and
urinary
radioactivity
accounted
for
30­
40%
of
the
administered
dose.
The
elimination
half­
Page
57
of
59
life
was
estimated
as
12
hours
for
male
rats
and
15
hours
for
females
rats.
For
the
high
dose
group,
the
urinary
radio
activity
represented
less
than
20%
of
the
administered
dose,
suggesting
saturation
of
absorption
or
elimination
processes.
Urinary
metabolites
included
haloaniline,
3­
phenoxybenzoic
acid
A,
lactone
of
anilino
A,
3­
phenoxybenzyl
alcohol,
diacid
and
3­(
4"­
hydroxyphenoxy)
benzoic
acid
A.
The
major
urinary
metabolites
were
3­(
4"­
hydroxyphenoxy)
benzoic
acid
A,
and
3­
phenoxybenzoic
acid
A.
Residues
in
various
tissues
and
the
carcass
at
96
hours
after
dosing,
accounted
for
only
2­
8%
of
the
administered
dose.
Although
sex
related
differences
in
the
metabolism
of
tau­
fluvalinate
were
detected,
none
were
considered
significant.
Pretreatment
with
the
chemical
(
Group
B)
did
not
significantly
affect
the
metabolism
and
disposition
of
tau­
fluvalinate.

This
study
is
classified
as
Acceptable/
Guideline
and
satisfies
the
requirement
for
a
series
85­
1
general
metabolism
study
in
rats.
Page
58
of
59
3.0
Tolerance
Reassessment
Summary;
Codex/
International
Harmonization
Tolerance
Reassessment
Summary
for
Tau­
Fluvalinate.

Commodity
Current
Tolerance
(
ppm)
Range
of
Residues
(
ppm)
Tolerance
Reassessment
(
ppm)
Comment/[
Correct
Commodity
Definition]

Tolerance
Listed
Under
40
CFR
§
180.427
(
a):

Honey
0.05
<
0.01­
0.015
0.02
No
Codex
MRLs
have
been
established
for
tau­
fluvalinate;
therefore,
issues
of
compatibility
between
Codex
MRLs
and
U.
S.
tolerances
do
not
exist.
A
Mexican
MRL
of
0.1
mg/
kg
has
been
established
for
cottonseed.
No
Canadian
MRLs
have
been
established
for
fluvalinate
or
taufluvalinate
We
note
that
tau­
fluvalinate
is
registered
for
use
in
Canada
in
honey
bee
chambers;
this
use
presumably
falls
under
the
PMRA
General
MRL
of
0.1
mg/
kg.
[
Regulation
B.
15.002(
1)
of
the
Canadian
Food
and
Drugs
Regulations
(
FDR)
establishes
0.1
ppm
as
the
"
General
Maximum
Residue
Limit."
This
regulation
states
that
a
food
is
adulterated
if
it
contains
residues
of
a
pesticide
at
a
level
greater
than
0.1
ppm
unless
a
specific
MRL
has
been
established
in
Table
II,
Division
15
of
the
FDR.]
Page
59
of
59
Confidential
Appendix
This
appendix
has
been
removed
to
a
separate
file
so
that
it
can
be
stored
on
the
RAD
database.