Document ID: EPA-HQ-OPP-2005-0181-0014
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-03-22T05:00Z

Page
1
of
40
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
MEMORANDUM
DATE:
September
29,
2005
SUBJECT:
Para­
tertiary
amylphenol
(
4­
t­
amylphenol)
and
its
sodium
and
potassium
salts:
AD
Risk
Assessment
for
the
Reregistration
Eligibility
Decision
(
RED)
Document.
Chemical
Nos.
064101,
064111,
064112.
Case
No.
3016.
DP
Barcode:
D316280
FROM:
Deborah
Smegal,
MPH,
Toxicologist/
Risk
Assessor
Myron
Ottley,
Ph.
D.,
Toxicologist
Tim
McMahon,
Ph.
D.
Senior
Toxicologist
Siroos
Mostaghimi,
Ph.
D.
Environmental
Engineer
Najm
Shamim,
Ph.
D.
Chemist
Srinivas
Gowda,
Microbiologist/
Chemist
David
C.
Bays
Jonathan
Chen,
PhD.,
Toxicologist
Antimicrobials
Division
(
7510C)

THRU:
Norm
Cook,
Chief
Risk
Assessment
and
Science
Support
Branch
Antimicrobials
Division
(
7510C)

TO:
Killian
Swift,
Risk
Manager
Reviewer
Team
36,
Reregistration
Antimicrobials
Division
(
7510C)

Attached
is
the
Revised
Risk
Assessment
for
Para­
tertiary
amylphenol
(
4­
t­
amylphenol)
and
its
sodium
and
potassium
salts
for
the
purpose
of
issuing
a
Reregistration
Eligibility
Decision
(
RED).
The
disciplinary
science
chapters
and
other
supporting
documents
for
the
4­
t­
amylphenol
RED
are
also
included
as
attachments
as
follows:
Page
2
of
40
4­
t­
Amylphenol:
Report
of
the
Antimicrobials
Divisions's
Toxicology
Endpoint
Selection
Committee
(
ADTC),
July
2005
Toxicology
Science
Chapter
for
the
Reregistration
Eligibility
Decision
Document,
From
M.
Ottley/
D.
Smegal
to
K.
Swift,
September
2005
D316279
Occupational
and
Residential
Exposure
Assessment
for
t­
Tert­
Amylphenol
and
Salts.
S.
Mostaghimi
.
September
2005.
D316290
Product
Chemistry
of
Para­
Tertiary­
Amylphenol,
para­
tertiary­
amylphenol,
sodium
salt
and
para­
tertiary­
amylphenol,
potassium
salt.
From
A.
N.
Shamim
to
T.
McMahon.
D316275
Revised
Environmental
Fate
Assessment
of
4­
tert­
Amylphenol
and
its
Potassium
and
Sodium
salts
for
the
Reregistration
Eligibility
Decision
(
RED)
Document.
From
S.
Gowda,
Microbiologist
to
M.
Hartman.
September
29
2005,
D322006
Ecological
Hazard
and
Environmental
Risk
Assessment
for
4­
tert­
amylphenol
and
salts
to
be
included
in
the
RED.
D.
Bays
to
A.
Heyward
and
K.
Swift.
October
2005,
D316278
Incident
Reports
Associated
with
4­
tert­
amylphenol.
J.
Chen.
May
2005,
D316276
Dietary
Exposure
Assessments
for
the
Reregistration
Eligibility
Decision.
R.
Quick.
September
29,
2005.
D316295.
Page
3
of
40
1.0
EXECUTIVE
SUMMARY....................................................................................................................
4
2.0
PHYSICAL
AND
CHEMICAL
PROPERTIES..................................................................................
11
3.0.
ENVIRONMENTAL
FATE................................................................................................................
12
4.0
HAZARD
CHARACTERIZATION....................................................................................................
13
4.1
Hazard
Profile
...........................................................................................................................
13
4.2
FQPA
Considerations..............................................................................................................
16
4.3
Dose­
Response
Assessment
.....................................................................................................
17
4.4
Endocrine
Disruption
..............................................................................................................
18
5.0
EXPOSURE
ASSESSMENT
AND
CHARACTERIZATION............................................................
19
5.1
Summary
of
Registered
Uses
...................................................................................................
19
5.2
Dietary
Exposure
and
Risk
......................................................................................................
19
5.3
Drinking
Water
Exposure
and
Risk..........................................................................................
21
5.4
Residential
Exposure/
Risk
Pathway.........................................................................................
22
5.4.1
Residential
Handler...........................................................................................................
22
5.4.2
Postapplication
Residential
Exposure
................................................................................
23
6.0
AGGREGATE
RISK
ASSESSMENTS
AND
RISK
CHARACTERIZATION..................................
26
6.1
Short­
and
Intermediate­
Term
Aggregate
Risk
.......................................................................
27
6.2
Long­
Term
Aggregate
Risk
...................................................................................................
28
7.0
CUMULATIVE
EXPOSURE
AND
RISK...........................................................................................
28
8.0
OCCUPATIONAL
EXPOSURE
AND
RISK......................................................................................
28
9.0
INCIDENTS.........................................................................................................................................
30
10.0
ENVIRONMENTAL
RISK.................................................................................................................
31
11.0
DEFICIENCIES/
DATA
NEEDS.........................................................................................................
36
12.0
REFERENCES
....................................................................................................................................
37
Page
4
of
40
1.0
EXECUTIVE
SUMMARY
4­
tertiary­
amylphenol
(
4­
t­
amylphenol),
and
salts
(
potassium
and
sodium)
are
active
ingredients
in
disinfectant,
food­
contact
sanitizer
and
deodorizer
products
used
in
agricultural,
food
handling,
commercial/
institutional/
industrial,
residential
and
public
access,
and
medical
settings,
primarily
used
on
hard,
non­
porous
surfaces.
The
majority
of
the
products
are
virucidal,
fungicidal,
tuberculocidal,
bactericidal,
pseudomonacidal,
or
staphylocidal.
Examples
of
registered
uses
for
4­
t­
amylphenol
and
salts
include
application
to
hard
surfaces
(
e.
g.,
walls,
floors,
tables,
fixtures),
textiles
(
e.
g.,
clothing,
diapers,
mattresses,
bedding),
carpets,
medical
instruments,
and
agricultural
equipment.
Additionally,
there
are
registered
uses
for
fogging
in
occupational
settings
and
air
deodorization
in
both
occupational
and
residential
settings.
Concentrations
of
4­
t­
amylphenol
and
salts
in
products
range
from
0.0027%
to
10%.
The
products
are
formulated
as
soluble
concentrates,
ready­
to­
use
liquid
solutions,
pressurized
sprays,
and
impregnated
wipes.

A
potential
outdoor
use,
wood
protection
to
treat
unseasoned
forest
products,
is
apparently
no
longer
supported
by
any
registrant.
In
addition,
the
registrant
is
no
longer
supporting
uses
in
potable
human
drinking
water
systems.

Hazard:
The
toxicology
database
for
4­
t­
amylphenol,
in
terms
of
guideline
studies,
is
largely
incomplete.
Studies
from
the
open
literature
provide
limited
information,
and
more
data
are
needed
to
put
together
a
complete
profile.

4­
t­
Amylphenol
is
a
primary
dermal
irritant
(
Category
I)
and
is
in
Category
III
for
acute
oral
toxicity
based
on
guideline
studies.
It
also
appears
to
be
an
eye
irritant
(
Category
I),
and
may
be
in
Category
III
for
acute
dermal
toxicity
according
to
data
from
the
open
literature.
However,
acceptable
guideline
acute
studies
are
not
available
for
dermal,
inhalation,
primary
eye
irritation
or
dermal
sensitization,
and
the
literature
data
protocols
were
inadequate.
Literature
studies
also
indicate
it
is
a
skin
sensitizer
and
possible
depigmentation
agent.
In
short­
term
studies,
4­
t­
amylphenol
produced
clinical
signs
along
with
decreased
food
consumption
and
body
weight
in
a
developmental
toxicity
study,
but
no
systemic
effects
in
a
13­
week
dermal
study.
The
structural
abnormalities
and
developmental
delays
that
occurred
in
the
developmental
study,
occurred
at
higher
dose
levels
than
the
maternal
effects,
suggesting
that
increased
quantitative
susceptibility
concerns
are
not
warranted;
however,
the
minimal
maternal
effects
(
reversible
clinical
signs)
seen
in
the
presence
of
the
developmental
effects
increases
concern
for
qualitative
susceptibility.
Neither
a
developmental
study
in
rabbits
nor
a
reproduction
study
was
available
to
provide
confirmation.
Available
data
suggest
that
4­
t­
amylphenol
has
endocrine
disrupter
capabilities
(
uterotrophic
and
estrogenic
effects)
and
increased
bilirubin
production
in
babies.
In
addition,
this
chemical
is
listed
on
a
European
list
of
"
Chemicals
purported
to
be
endocrine
disruptors".

4­
t­
Amylphenol
was
negative
for
carcinogenicity
in
a
subchronic
skin
painting
study
from
the
open
literature.
However,
guideline
studies
for
carcinogenicity
are
not
available.
All
mutagenicity
tests
were
negative.

Toxicity
Endpoints:
The
toxicity
endpoints
used
in
this
document
to
assess
potential
risks
Page
5
of
40
include
acute
and
chronic
dietary
reference
doses
(
RfDs),
and
short­,
intermediate­
and/
or
long­
term
incidental
oral,
dermal
and
inhalation
doses.
The
Antimicrobials
Division's
endpoint
selection
committee
(
ADTC)
selected
endpoints
in
April
2005.
Since
the
toxicological
endpoints
selected
for
4­
tert­
amylphenol
and
4­
tert­
amylphenol
salts
are
identical,
a
separate
assessment
was
not
conducted
for
each
active
ingredient.

Acute
and
Chronic
RfDs:
The
acute
RfD
is
0.67
mg/
kg/
day
for
females
(
13­
50
years,
based
on
adverse
developmental
effects
(
skeletal
effects
and
decreased
fetal
body
weight)
at
500
mg/
kg/
day
in
a
rat
developmental
study.
The
chronic
RfD
is
0.17
mg/
kg/
day
based
on
clinical
signs
of
toxicity
and
decreased
body
weight
and
food
consumption
at
200
mg/
kg/
day
in
a
rat
developmental
study.
An
uncertainty
factor
of
300
(
10X
for
interspecies
extrapolation,
10X
for
intraspecies
variability,
and
3X
for
database
uncertainties)
was
applied
to
the
NOAEL
to
obtain
the
acute
and
chronic
RfDs.
A
database
uncertainty
factor
of
3x
is
applied
to
non­
occupational
risk
assessments
for
4­
t­
amylphenol,
due
to
the
number
and
significance
of
the
data
gaps
including
lack
of
repeated
oral
toxicity
studies.
An
additional
Food
Quality
Protection
Factor
(
FQPA)
safety
factor
is
applied,
which
is
discussed
below.

Incidental
oral
endpoints:
The
short­
and
intermediate­
term
incidental
oral
NOAEL
is
50
mg/
kg/
day
from
a
rat
oral
developmental
toxicity
study
that
noted
clinical
signs,
decreases
in
body
weight
and
body
weight
gain,
coupled
with
decreased
food
consumption
at
200
mg/
kg/
day.
The
target
margin
of
exposure
(
MOE)
is
3,000
(
includes
10X
FQPA
factor).

Dermal
endpoints:
The
short­
and
intermediate­
term
dermal
NOAEL
is
25
mg/
kg/
day,
which
is
based
on
the
lack
of
systemic
effects
identified
up
to
and
including
a
dose
of
25
mg/
kg/
day
in
a
rat
subchronic
dermal
toxicity
study.
Uncertainty
factors
or
"
target"
margins
of
exposure
(
MOE)
for
4­
t­
amylphenol
dermal
exposures
are
100
for
occupational
scenarios
and
1,000
for
residential
scenario
(
includes
10X
FQPA
factor).
It
should
be
noted
that
4­
t­
amylphenol
caused
dermal
irritant
effects
following
repeated
dermal
exposure
at
10
mg/
kg/
day,
and
may
also
be
a
potential
dermal
sensitizer.

Inhalation
endpoints:
The
short­,
intermediate­
and
long­
term
inhalation
NOAEL
is
50
mg/
kg/
day
from
a
rat
oral
developmental
toxicity
study
that
noted
clinical
signs,
decreases
in
body
weight
and
body
weight
gain,
coupled
with
decreased
food
consumption
at
200
mg/
kg/
day.
In
the
absence
of
data,
it
was
conservatively
assumed
that
inhalation
absorption
is
equivalent
to
oral
absorption
(
i.
e.,
100%).
For
inhalation
exposures,
the
uncertainty
factors
are
300
for
occupational
scenarios
and
3,000
for
residential
scenarios
(
includes
10X
FQPA
factor).

FQPA
Safety
Factor.
The
ADTC
committee
concluded
that
the
hazard
based
FQPA
safety
factor
should
be
retained
at
10X.
The
toxicology
data
base
is
not
complete
with
respect
to
assessing
the
increased
susceptibility
to
infants
and
children
as
required
by
FQPA
for
4­
t­
amylphenol.
The
rat
prenatal
developmental
study
showed
no
quantitative
evidence
of
increased
susceptibility
(
i.
e.,
developmental
NOAELs/
LOAELs
were
the
higher
than
those
for
maternal
effects).
However,
there
was
qualitative
evidence
of
increased
susceptibility
as
the
fetal
effects
(
i.
e.,
skeletal
abnormalities,
decreased
body
weight
gain)
were
considered
to
be
more
severe
than
the
maternal
toxicity
(
reversible
clinical
signs).
In
addition,
there
is
an
absence
of
developmental
toxicity
data
in
the
rabbit,
and
an
absence
of
reproductive
toxicity
data.
Page
6
of
40
Furthermore,
studies
in
the
open
literature
suggest
that
4­
t­
amylphenol
may
be
an
endocrine
disruptor.
It
increased
non­
pregnant
uterine
weight
in
rats
and
was
associated
with
elevated
blood
levels
of
bilirubin
in
children
exposed
to
4­
t­
ampyphenol
and
other
phenols
in
disinfectant.
These
studies,
while
not
indicative,
are
suggestive
of
a
basis
for
increased
concern
for
reproductive
and/
or
developmental
effects
due
to
exposure
to
4­
t­
amylphenol.
In
addition,
this
chemical
is
listed
on
a
European
list
of
"
Chemicals
purported
to
be
endocrine
disruptors".

Based
on
Agency
policy,
a
RfD
modified
by
a
FQPA
safety
factor
is
a
population
adjusted
dose
(
PAD)
1
FQPA
Safety
Factor.
The
Agency
calculated
an
acute
PAD
and
a
chronic
PAD,
and
uses
this
value
to
estimate
acute
and
chronic
dietary
risk.

Dietary
Exposure
and
Risk:
The
Agency
has
conducted
a
dietary
exposure
and
risk
assessment
for
use
of
4­
t­
amylphenol
in
a
ready­
to­
use
disinfecting
solution.
A
counter
top
that
is
treated
with
this
product
may
come
into
contact
with
food,
which
in
turn
may
be
ingested.
This
is
considered
to
be
an
indirect
food
use.
4­
t­
Amylphenol
(
also
known
as
phenol,
4­
1,1­
dimethylpropyl)
(
CAS
No.
80­
46­
6)
has
a
tolerance
exception
in
40CFR
180.940
(
c)
as
a
food­
contact
sanitizer
for
use
in
food­
processing
equipment
and
utensils
with
a
not
to
exceed
limit
of
80
ppm.
However,
the
maximum
ingredient
percentage
for
4­
t­
amylphenol
in
food
handling
establishments
from
the
various
labeled
ready­
to­
use
products
is
0.054
%
a.
i
(
540
ppm),
which
exceeds
the
current
tolerance
exemption
limitation.
The
Agency
estimates
that
use
of
this
product
results
in
4­
t­
amylphenol
food
residues
of
340
ppb
(
µ
g/
kg).

When
assessing
acute
and
chronic
(
non­
cancer)
dietary
risk,
AD
considered
potential
dietary
exposure
to
the
U.
S.
population
including
infants
and
children,
as
well
as
to
females
of
childbearing
age
(
13­
50
years).
AD
expresses
dietary
risk
estimates
as
a
percentage
of
the
aPAD
or
chronic
PAD.
Dietary
exposures
that
are
less
than
100%
of
the
aPAD
or
cPAD
are
below
the
Agency's
level
of
concern.

Acute
Dietary
Risk.
AD
has
determined
that,
based
on
the
assumptions
and
models
used,
the
acute
dietary
risk
from
exposure
to
4­
t­
amylphenol
does
not
exceed
the
Agency's
level
of
concern
for
females
of
childbearing
age,
the
only
subpopulation
examined.
The
dietary
risk
estimate
is
2.7%
of
the
acute
PAD.

Chronic
Dietary
Risk.
In
the
absence
of
data,
screening
level
estimates
used
for
the
acute
dietary
risk
analysis
are
used
to
assess
potential
chronic
dietary
exposure.
The
risk
analysis
assumes
daily
exposure
from
the
hard
surface
disinfection
of
counter
tops.
The
chronic
non­
cancer
dietary
analysis
indicates
all
risk
estimates
are
below
the
Agency's
level
of
concern
for
all
population
subgroups.
The
highest
dietary
risk
estimate
is
42%
of
the
chronic
PAD,
for
infants
and
children,
assuming
10%
of
the
residues
are
transferred
to
food.
The
Agency
requires
confirmatory
data
for
this
transfer
rate
because
100%
residue
transfer
indicates
risks
of
concern.

Water
Exposure
and
Risk:
There
are
no
currently
registered
outdoor
uses
of
4­
t­
amylphenol
and
its
salts
that
are
being
supported
by
the
registrant.
The
potential
outdoor
uses,

1
PAD
=
Population
Adjusted
Dose
=
Acute
or
Chronic
RfD
FQPA
Safety
Factor
Page
7
of
40
wood
protection
to
treat
unseasoned
forest
products,
and
use
in
potable
human
drinking
water
systems
are
apparently
no
longer
supported
by
any
registrant.
4­
t­
Amylphenol's
use
as
a
general
disinfectant
allows
for
the
possibility
of
surface
water
contamination.
However,
the
estimated
value
for
biodegradation
indicates
it
may
biodegrade
linearly
within
days
in
the
aquatic
environment,
although
ultimate
biodegradation
(
mineralization)
may
take
months.
The
sodium
and
potassium
salts
of
4­
t­
amylphenol
are
estimated
to
biodegrade
within
days
to
weeks.
Because
of
the
possibility
of
biodegradation
in
water
and
soils,
4­
t­
amylphenol
and
its
salts
are
not
likely
to
contaminate
surface
and
ground
waters.
Thus,
a
quantitative
drinking
water
assessment
was
not
conducted
for
these
chemicals.

Residential
(
Non­
Occupational)
Exposure
and
Risk:
Some
products
containing
4­
t­
amylphenol
are
labeled
for
residential
use
as
disinfectants
and
deodorizers.
These
products
are
for
use
on
hard
surfaces
(
e.
g.,
floors,
walls,
bathroom
fixtures,
trash
cans,
household
contents),
textiles
(
e.
g.,
clothing,
diapers,
and
bedding),
and
carpets.
Additionally,
there
are
products
which
can
be
used
to
deodorize
air
in
the
home.
There
are
no
residential
uses
for
products
containing
sodium
4­
tert­
amylphenate
or
potassium
4­
tert­
amylphenate.
The
following
scenarios
were
considered
for
residential
handlers:
application
of
hard
surface
disinfectants
via
(
1)
mopping;
(
2)
wiping;
(
3)
trigger
pump
spray;
and
(
4)
aerosol
spray.

The
Agency
also
evaluated
potential
postapplication
exposures
to
products
that
contain
4­
t­
amylphenol.
Postapplication
scenarios
evaluated,
which
were
considered
to
be
representative
of
all
possible
exposure
scenarios,
included:
contact
with
treated
hard
surfaces/
flooring
by
children
(
incidental
oral
and
dermal
exposure),
dermal
contact
with
treated
textiles
and
diapers,
incidental
ingestion
of
treated
textiles,
and
postapplication/
bystander
inhalation
exposure
from
use
of
disinfecting/
deodorizing
products.
Duration
of
exposure
is
short­
term
(
1­
30
days)
and
intermediate­
term
(
1­
6
months)
for
all
residential
scenarios
assessed,
except
for
the
diaper
use,
which
is
also
considered
to
be
a
long­
term
scenario
(>
6
months).
The
scenarios
were
evaluated
based
on
the
Residential
Exposure
Assessment
Standard
Operating
Procedures
(
SOPs),
product
label
maximum
application
rates,
related
use
information,
Agency
standard
assumptions,
inhalation
and
dermal
unit
exposure
data
from
the
proprietary
Chemical
Manufactures
Association
(
EPA
1999,
CMA,
1992),
and
Pesticide
Handlers
Exposure
Database
(
PHED).
In
addition,
the
Multi­
Chamber
Concentration
and
Exposure
Model
(
MCCEM)
was
used
to
estimate
postapplication
inhalation
exposure
to
air
deodorizer.
At
this
time,
EPA
does
not
have
available
chemical­
specific
handler
or
postapplication
exposure
studies
that
meet
Agency
guidelines.

Residential
Handler
Risk
Summary.
For
the
residential
handler
dermal
and
inhalation
risk
assessment,
short­
and
intermediate­
term
risks
for
all
scenarios
evaluated
are
above
the
respective
target
MOEs
for
all
scenarios
(
i.
e.,
dermal
MOEs
were
>
1,000
and
inhalation
MOEs
were
>
3,000),
and
thus
are
not
of
concern.

Postapplication
Residential
Risk
Summary.
For
the
residential
postapplication
scenarios
assessed
in
this
document,
risk
estimates
that
exceed
the
Agency's
level
of
concern
(
i.
e.,
dermal
MOEs
<
1,000,
inhalation
MOEs
<
3,000,
and
oral
MOEs
<
3,000)
are:

°
Incidental
oral
exposure
from
children
mouthing
treated
textiles
(
oral
MOE=
650);
Page
8
of
40
°
Dermal
exposure
from
children
wearing
treated
clothing
(
Dermal
MOE
=
0.86
with
a
100%
transfer
factor
and
Dermal
MOE
=
17
with
a
5%
transfer
factor);
°
Dermal
exposure
from
children
wearing
a
treated
diaper
(
Dermal
MOE
=
59
with
a
100%
transfer
factor
and
Dermal
MOE
=
1,200
with
a
5%
transfer
factor,
which
is
above
the
target
MOE);
°
Dermal
exposure
from
children
playing
on
a
treated
hard
surface
in
a
daycare
center
(
Dermal
MOE
=
940);
°
Dermal
exposure
from
adults
wearing
treated
clothing
(
Dermal
MOE
=
140
with
a
100%
transfer
factor;
however,
with
a
5%
transfer
factor
the
Dermal
MOE
=
2,700,
which
is
above
the
target
MOE).
The
Agency
will
require
confirmatory
data
to
support
a
5%
transfer
factor.

As
noted
previously,
4­
t­
amylphenol
also
caused
dermal
irritant
effects
following
repeated
dermal
exposure
at
10
mg/
kg/
day,
and
may
also
be
a
potential
dermal
sensitizer.
Since
the
MOEs
are
based
on
systemic
effects
at
25
mg/
kg/
day,
the
Agency
intends
to
consider
the
potential
for
irritation
and
sensitization
in
recommended
labeling
language
of
pesticide
products
containing
4­
t­
amylphenol,
and
additional
dermal
toxicity
data
on
a
diluted
end­
use
formulation.

Aggregate
Exposure
and
Risk:
In
order
for
a
pesticide
registration
to
continue,
it
must
be
shown
that
the
use
does
not
result
in
"
unreasonable
adverse
effects
on
the
environment".
Section
2
(
bb)
of
FIFRA
defines
this
term
to
include
"
a
human
dietary
risk
from
residues
that
result
from
a
use
of
a
pesticide
in
or
on
any
food
inconsistent
with
standard
under
section
408..."
of
FFDCA.
As
mandated
by
the
FQPA
amendments
to
FIFRA
and
the
Federal
Food,
Drug
and
Cosmetic
Act
(
FFDCA),
the
Agency
must
consider
total
aggregate
exposure
from
food,
drinking
water
and
residential
sources
of
exposure
to
4­
t­
amylphenol.

Oral
and
inhalation
exposure
and
risk
estimates
were
combined
for
the
aggregate
risk
assessment
because
the
toxicity
endpoint
is
identical
for
both
routes
of
exposure.
Dermal
residential
exposures
were
not
aggregated
with
the
oral
or
inhalation
exposures
due
to
different
toxicological
endpoints
for
oral
(
clinical
signs
and
body
weight
changes),
and
dermal
(
no
systemic
effects
at
the
highest
dose
tested).
Acute
and
chronic
aggregate
assessments
were
not
conducted
because
there
are
no
significant
impacts
to
drinking
water
sources
from
the
indoor
uses
of
4­
t­
amylphenol,
nor
are
there
long­
term
residential
uses.
Thus,
only
short­
and
intermediate­
term
aggregate
assessments
were
conducted.

Short
and
Intermediate
Term.
Short­
and
intermediate­
term
aggregate
risks
are
considered
together
since
the
exposure
and
toxicity
endpoints
are
identical
for
both
durations.
For
children,
the
short­
and
intermediate­
term
aggregate
assessment
includes
average
dietary
exposure
(
food)
and
estimated
incidental
oral
exposures
from
residential
uses
such
as
hard
surface
disinfection.
In
addition,
inhalation
exposures
from
the
postapplication
of
an
air
deodorizer
use
were
aggregated
with
the
oral
exposures
since
the
toxicity
endpoint
is
the
same
and
it
is
possible
that
the
scenarios
could
co­
occur.
For
adults,
the
aggregate
assessment
includes
dietary
(
oral)
and
residential
inhalation
exposures
from
wiping
a
hard
surface
disinfectant,
in
addition
to
postapplication
inhalation
exposure
from
the
air
deodorizer.

The
aggregate
oral
and
inhalation
risks
are
not
of
concern
for
adults,
as
the
total
aggregate
Page
9
of
40
MOE
is
13,000
which
is
greater
than
the
target
of
3,000.
For
children,
the
aggregate
risk
estimates
are
also
above
the
target
MOE
of
3000
(
MOE=
3,200),
and
thus
are
not
of
concern.
As
noted
previously,
incidental
oral
exposure
to
treated
textiles
are
not
included
in
the
aggregate
assessment
because
oral
MOE
is
already
of
concern
(
MOE=
650
versus
target
>
3000).
It
should
be
noted
that
several
conservative
assumptions
were
used
in
this
assessment.

A
dermal
aggregate
assessment
was
not
conducted.
However,
as
noted
previously,
shortand
intermediate
dermal
risks
are
already
of
concern
for
residents
for
the
treated
textile
and
diaper
use,
and
dermal
contact
with
residues
from
hard
surface
disinfectant
use.
The
Agency
will
request
confirmatory
data
to
verify
these
risk
estimates.

Long­
Term
Aggregate.
A
long­
term
aggregate
assessment
was
not
conducted
because
the
only
long­
term
residential
use
(
diaper
use)
results
in
dermal
exposure,
which
has
a
different
toxicological
effect
than
the
chronic
dietary
oral
exposure.

Occupational
Exposure
and
Risk.
Based
on
examination
of
product
labels
describing
uses
for
the
product,
it
has
been
determined
that
exposure
to
handlers
can
occur
in
a
variety
of
occupational
environments.
Additionally,
postapplication
exposures
are
likely
to
occur
in
these
settings.
The
representative
scenarios
selected
by
AD
for
assessment
were
evaluated
using
maximum
application
rates
as
recommended
on
the
product
labels
for
4­
t­
amylphenol.

To
assess
the
handler
risks,
AD
used
surrogate
unit
exposure
data
from
both
the
proprietary
Chemical
Manufacturers
Association
(
CMA)
antimicrobial
exposure
study
and
the
Pesticide
Handlers
Exposure
Database
(
PHED).
Additionally,
the
MCCEM
(
Multi­
Chamber
Concentration
and
Exposure
Model)
was
used
to
estimate
postapplication/
bystander
exposures.

For
the
occupational
handler
dermal
and
inhalation
risk
assessment,
the
short­
and
intermediate­
and
long­
term
risks
calculated
at
baseline
exposure
(
no
gloves
and
no
respirators)
were
above
target
MOEs
for
all
scenarios
(
i.
e.,
dermal
MOEs
were
>
100
and
inhalation
MOEs
were
>
300).
Note,
however,
that
the
high
pressure
spray
application
method
in
the
agricultural
use
site
category
was
assessed
using
gloved
data.

For
most
of
the
occupational
scenarios,
postapplication
dermal
exposure
is
not
expected
to
occur
or
is
expected
to
be
negligible
based
on
the
application
rates
and
chemical
properties
of
the
chemical.
Postapplication/
bystander
inhalation
exposures,
however,
were
assessed
for
entry
into
a
building
after
a
fogging
application.
The
representative
building
selected
was
a
poultry
barn.
The
calculated
inhalation
MOEs
were
above
the
target
MOE
of
300
for
all
fogging
postapplication
scenarios.

Other
Food
Quality
Protection
Act
(
FQPA)
Considerations
Cumulative
Effects.
Section
408
of
the
FFDCA
stipulates
that
when
determining
the
safety
of
a
pesticide
chemical,
EPA
shall
base
its
assessment
of
the
risk
posed
by
the
chemical
on,
among
other
things,
available
information
concerning
the
cumulative
effects
to
human
health
that
may
result
from
dietary,
residential,
or
other
non­
occupational
exposure
to
other
substances
that
have
a
common
mechanism
of
toxicity.
The
reason
for
consideration
of
other
substances
is
due
to
Page
10
of
40
the
possibility
that
low­
level
exposures
to
multiple
chemical
substances
that
cause
a
common
toxic
effect
by
a
common
mechanism
could
lead
to
the
same
adverse
health
effect
as
would
a
higher
level
of
exposure
to
any
of
the
other
substances
individually.
A
person
exposed
to
a
pesticide
at
a
level
that
is
considered
safe
may
in
fact
experience
harm
if
that
person
is
also
exposed
to
other
substances
that
cause
a
common
toxic
effect
by
a
mechanism
common
with
that
of
the
subject
pesticide,
even
if
the
individual
exposure
levels
to
the
other
substances
are
also
considered
safe.
EPA
does
not
have,
at
this
time,
available
data
to
determine
whether
4­
t­
amylphenol
and
its
salts
have
a
common
mechanism
of
toxicity
with
other
substances.

Endocrine
Disruption.
Available
data
for
4­
t­
amylphenol
suggest
is
has
endocrine
disruptor
capabilities
in
mammals
(
uterotrophic
and
estrogenic
effects)
and
increased
bilirubin
production
in
babies.
It
has
been
shown
to
affect
the
reproductive
process
of
carp.
The
Food
Quality
Protection
Act
(
FQPA;
1996)
requires
that
EPA
develop
a
screening
program
to
determine
whether
certain
substances
(
including
all
pesticides
and
inerts)
"
may
have
an
effect
in
humans
that
is
similar
to
an
effect
produced
by
a
naturally
occurring
estrogen,
or
such
other
endocrine
effect...."
Following
the
recommendations
of
its
Endocrine
Disruptor
Screening
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).

When
the
appropriate
screening
and/
or
testing
protocols
being
considered
under
the
Agency's
EDSP
have
been
developed
and
validated,
4­
t­
amylphenol
and
its
potassium
and
sodium
salts
may
be
subjected
to
additional
screening
and/
or
testing
to
better
characterize
effects
related
to
endocrine
disruption.

Environmental
Hazard
and
Risk.
The
registrant
has
not
submitted
any
ecological
effects
data
to
support
this
RED
for
4­
tert­
amylphenol
and
its
salts.
The
only
data
that
was
available
was
found
in
the
peer­
reviewed
literature.
None
of
these
studies
met
current
guideline
requirements
and
therefore,
could
not
be
used
in
a
risk
assessment.
There
is
a
concern
about
the
possibility
of
endocrine
disruption
in
fish,
since
4­
t­
amylphenol
is
considered
an
ecoestrogen.
This
was
documented
in
several
studies
on
carp
(
Cyprinus
carpio),
whose
findings
were
included
in
the
ecotoxicity
chapter.
However,
since
this
chemical
is
restricted
to
indoor
uses
only,
the
possibility
for
exposure
of
fish
to
4­
t­
amylphenol
would
be
limited.
The
registrant
does
have
to
submit
three
ecological
effects
studies
on
the
acute
toxicity
of
this
chemical.
These
include
an
avian
acute
oral
toxicity
test,
preferably
using
the
bobwhite
quail,
(
850.2100/
71­
1),
a
freshwater
fish
acute
toxicity
test,
preferably
using
the
rainbow
trout,
(
850.1075/
72­
1),
and
an
acute
freshwater
invertebrate
test
(
850.1010/
72­
2).
These
tests
are
required
in
order
to
document
potential
acute
toxicity
to
these
organisms
in
the
unlikely
event
that
exposure
to
4­
t­
amylphenol
and
its
salts
does
occur.
Page
11
of
40
2.0
PHYSICAL
AND
CHEMICAL
PROPERTIES
The
physical
and
chemical
properties
of
4­
t­
amylphenol
and
its
sodium
and
potassium
salts
are
provided
in
Table
1.

Structure
for
4­
t­
amylphenol:

OH
C
CH
3
CH
3
C
H
H
CH
3
O
­
Na
+
CH
3
CH
3
CH
3
Paratertiaryamyl
P
hen
o
l,
S
o
d
ium
S
alt
O
­
K
+
CH
3
CH
3
CH
3
P
a
rate
rtia
ry
P
h
en
o
l,
Po
tas
sium
S
alt
Table
1
Physical
and
Chemical
Properties
Property
4­
t­
amylphenol
Sodium
4­
tert­
amylphenate
Potassium
4­
tert­
amylphenate
PC
Chemical
Code
064101
064111
064112
Cas
Number
80­
46­
6
31366­
95­
7
53404­
18­
5
Molecular
Formula
C11H16O
C11H15NaO
C11H15KO
Page
12
of
40
Table
1
Physical
and
Chemical
Properties
Property
4­
t­
amylphenol
Sodium
4­
tert­
amylphenate
Potassium
4­
tert­
amylphenate
Synonyms
Para­
tert­
amylphenol,
1­
hydroxy­
4(
2­
methyl­
2­
butyl)

benzene;
p­(
1,1­
dimethylpropyl)
phenol;
p­(
alpha,
alpha­
dimethylpropyl)

phenol
Molecular
Weight
164.25
186.23
202.34
Melting
Point
95
o
C
205
o
C
(
estimated)
206
o
C
Boiling
Point
263
o
C
485
o
C
(
estimated)
486
o
C
Vapor
Pressure
1.16
x
10­
3
mm
Hg
at
25
o
C
7.7
x10­
10
(
estimated)
at
25
o
C
7.7
x10­
10
mm
Hg
at
25
o
C
(
estimated)

Solubility
(
water)
113.4
mg/
L
4595
mg/
L
(
estimated)
3811
mg/
L
at
25
o
C
(
estimated)

Henry
Law
Constant
(
HLC)
2.03
x
10­
6
atm­
m3/
mol
(
estimated)
4.10
x
10­
14
atm­
m3
/
mole
(
estimated)
5.38
x
10­
14
atm­
m3
/
mole
(
estimated)

Log
Koc
3.57
(
estimated)
3.57
3.57
(
estimated)

Log
Kow
3.91
1.23
1.23
(
estimated)

Physical
State
White
Solid
Solid
Solid
Persistence
in
Air
(
t
½

in
Air)
3.073
hours
(
measured
against
hydroxy
radical)
4.67
hours
(
measured
against
hydroxy
radical
4.67
hours
(
measured
against
hydroxy
radical)

3.0.
ENVIRONMENTAL
FATE
Detailed
information
on
environmental
fate
is
presented
in
the
attached
memo
from
S.
Gowda
(
September
2005).
A
brief
summary
is
provided
below.

The
environmental
fate
assessment
for
4­
t­
amylphenol
and
its
potassium
and
sodium
salts
is
based
on
US
EPA
=

s
Estimation
Programs
Interface
(
EPI)
Suite.
EPI
Suite
provides
estimations
of
physical/
chemical
properties
and
environmental
fate
properties.

4­
t­
Amylphenol
may
be
bioaccumlative
(
log
KOW
3.91)
and
is
likely
to
pose
a
concern
for
aquatic
organisms.
It
is
expected
to
have
moderate
to
slight
mobility
in
soils
based
upon
the
estimated
Koc
value
of
3799.
Estimated
value
for
biodegradation
probability
indicates
that
it
may
biodegrade
linearly
within
days
in
aquatic
medium.
However,
ultimate
biodegradation
(
mineralization)
may
take
months.
It
is
volatile
and
may
vaporize
into
the
atmosphere.
The
estimated
half
life
in
the
air
for
4­
t­
Amylphenol
is
about
three
hours
which
indicates
that
it
is
not
persistent
in
air.
Because
of
the
possibility
of
biodegradation
in
water
and
soils,
it
is
not
likely
to
contaminate
surface
and
ground
waters.
Page
13
of
40
4­
t­
Amylphenol,
potassium
salt,
is
not
likely
to
be
bioaccumlative
(
log
KOW
1.23)
and
may
not
pose
a
concern
for
bioconcentration
in
aquatic
organisms.
It
may
be
expected
to
have
moderate
to
slight
mobility
in
soils
as
its
estimated
Koc
value
is
3799.
Estimated
probability
of
biodegradation
of
4­
t­
Amylphenol,
potassium
salt,
in
soils
and
water
indicates
that
it
is
likely
to
biodegrade
within
days
to
weeks.
Therefore,
it
may
be
unlikely
that
soil
and
water
contamination
would
take
place.
It
has
low
volatility
and
its
estimated
half
life
in
air
is
about
4.68
hours
and
is
not
likely
to
be
persistent
in
air.

4­
t­
Amylphenol,
sodium
salt,
is
not
likely
to
be
bioaccumlative
(
log
KOW
is
1.23)
and
may
not
pose
a
concern
for
bioconcentration
in
aquatic
organisms.
It
may
be
expected
to
have
moderate
to
slight
mobility
in
soils
as
its
estimated
Koc
value
is
the
same
as
the
parent
molecule,
4­
t­
Amylphenol.
Probability
for
sodium
4­
tert­
amylphenate
biodegradation
is
the
same
as
the
parent
molecule,
4­
t­
amylphenol.
Hence,
it
is
not
likely
to
persist
in
soils
and
water,
and
surface
and
ground
water
contamination
is
not
likely
to
occur.
It
has
low
volatility
and
its
estimated
half
life
in
air
is
about
4.68
hours
and
is
not
likely
to
be
persistent
in
air.

4.0
HAZARD
CHARACTERIZATION
4.1
Hazard
Profile
The
toxicology
database
for
4­
t­
amylphenol,
in
terms
of
guideline
studies,
is
largely
incomplete.
Studies
from
the
open
literature
provide
useful
information,
but
more
data
are
needed
to
put
together
a
complete
profile.

A
detailed
hazard
assessment
for
4­
t­
amylphenol
and
its
salts
is
presented
in
the
attached
memorandum
(
memo
from
M.
Ottley/
D.
Smegal,
September
2005).
4­
t­
Amylphenol
is
a
primary
dermal
irritant
(
Category
I)
and
is
in
Category
III
for
acute
oral
toxicity
based
on
guideline
studies.
It
also
appears
to
be
an
eye
irritant
(
Category
I),
and
may
be
in
Category
III
for
acute
dermal
toxicity
according
to
data
from
the
open
literature.
However,
acceptable
guideline
acute
studies
are
not
available
for
dermal,
inhalation,
primary
eye
irritation
or
dermal
sensitization,
and
the
literature
data
protocols
were
inadequate.

In
short­
term
studies,
4­
t­
amylphenol
produced
clinical
signs
along
with
decreased
food
consumption
and
body
weight
in
a
developmental
toxicity
study,
but
no
systemic
effects
in
a
13­
week
dermal
study.
The
structural
abnormalities
and
developmental
delays
that
occurred
in
the
developmental
study,
occurred
at
higher
dose
levels
than
the
maternal
effects,
suggesting
that
increased
quantitative
susceptibility
concerns
are
not
warranted;
however,
the
minimal
maternal
effects
(
reversible
clinical
signs)
seen
in
the
presence
of
the
developmental
effects
increases
concern
for
qualitative
susceptibility.
Neither
a
developmental
study
in
rabbits
nor
a
reproduction
study
was
available
to
provide
confirmation.

Available
data
suggest
that
4­
t­
amylphenol
has
endocrine
disrupter
capabilities
(
uterotrophic
and
estrogenic
effects)
and
increased
bilirubin
production
in
babies.
In
addition,
this
chemical
is
listed
on
a
European
list
of
"
Chemicals
purported
to
be
endocrine
disruptors"
(
IEH
2005).
When
taken
with
the
lack
of
available
developmental
and
reproductive
toxicity
data,
Page
14
of
40
concerns
for
FQPA
issues
are
heightened.

No
dermal
penetration
studies
were
available
for
4­
t­
amylphenol,
and
an
extrapolation
between
the
13­
week
dermal
study
and
the
oral
developmental
study
does
not
seem
possible,
for
the
purposes
of
estimating
dermal
absorption.

4­
t­
Amylphenol
was
negative
for
carcinogenicity
in
a
subchronic
skin
painting
study
from
the
open
literature.
However,
guideline
studies
for
carcinogenicity
are
not
available.
All
mutagenicity
tests
were
negative.
Tables
2
and
3
highlight
key
toxicological
studies
for
4­
t­
amylphenol.

Table
2
Acute
Toxicity
Studies
for
4­
t­
Amylphenol
Technical
Guideline
No./
Study
Type
MRID
No.
Results
Toxicity
Category
870.1100
Acute
oral
toxicity
46616601
LD50
>
2000
mg/
kg
for
males
and
females
III
870.1200
Acute
dermal
toxicity
NA
[
]

870.1300
Acute
inhalation
toxicity
NA
[
]

870.2400
Acute
eye
irritation
NA
No
adequate
acute
toxicity
studies
were
provided
or
identified
in
the
open
literature.

[
]

870.2500
Acute
dermal
irritation
46616602
Corrosive
following
4
hour
application;
scar
tissue
noted
14
days
after
treatment
I
870.2600
Skin
sensitization
NA
Table
3
Toxicity
Profile
of
4­
t­
Amylphenol
Technical
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
870.3250
90­
Day
dermal
toxicity
MRID
42470301
(
1993)
0,
2.5,
10,
25
mg/
kg/
day
not
acceptable,
no
systemic
toxicity
demonstrated
NOAEL
=
2.5
mg/
kg/
day
LOAEL
=
10
mg/
kg/
day
based
on
dermal
effects
870.3700a
Prenatal
developmental
in
rodents
41920002
(
1991)
Acceptable
0,
50,
200,
500
mg/
kg/
day
Maternal
NOAEL
=
50
mg/
kg/
day
LOAEL
=
200
mg/
kg/
day
based
on
clinical
signs
and
decreased
body
weight,
weight
gain,
and
food
consumption
Developmental
NOAEL
=
200
mg/
kg/
day
LOAEL
=
500
mg/
kg/
day
based
on
decreased
fetal
body
weight
and
increased
incidence
of
bent
ribs
Page
15
of
40
Table
3
Toxicity
Profile
of
4­
t­
Amylphenol
Technical
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
Gene
Mutation
870.5265
Salmonella
typhimurium
reverse
mutation
assay
414384­
01
(
1990)
Acceptable
1,
3.2,
10,
31.6,
and
100

ug/
plate
Negative,
with
or
without
activation
Gene
Mutation
870.5300
In
vitro
mammalian
cell
gene
mutation
test
415727­
01
(
1990)
Acceptable
non­
activated
conditions
­
5,
10,
20,
30,
and
40

g/
ml;
activated
conditions
­
2,
4,
6,
8,
and
10
ug/
ml
Negative
with
and
without
metabolic
activation.
The
few
positive
results
in
control
plates
are
consistent
with
historical
control
data
for
the
laboratory
and
test
system.

Cytogenetics
870.5395
Mammalian
erythrocyte
micro­
nucleus
test
417108
(
1990)
Acceptable
62.5
(
M),
250
(
M+
F),
1000
(
M+
F),
and
4000
mg/
kg
(
F)
Negative
Skin
Sensitization.
P­
tert­
amylphenol
has
been
reported
to
be
a
skin
sensitizer
and
depigmenting
agent
(
BIBRA
Working
Group,
1990).
Stevenson
(
1984),
however,
reported
p­
t­
amylphenol
to
have
a
"
low
depigmenting
potential"
because
none
of
129
men
who
had
been
exposed
to
the
compound
during
its
manufacture
exhibited
depigmentation.

Developmental
Toxicity.
The
data
base
for
developmental
toxicity
is
adequate
only
for
non­
food
uses
of
4­
t­
amylphenol.
Additional
data
are
required
for
indirect
food
use.
The
one
study
provided,
a
prenatal
developmental
toxicity
study
in
rats,
indicated
a
lower
NOAEL
and
LOAEL
for
maternal
toxicity
(
i.
e.,
50
and
200
mg/
kg­
day)
than
for
developmental
toxicity
(
i.
e.,
200
and
500
mg/
kg­
day),
and
the
developmental
effects
were
not
frankly
teratogenic.
Thus,
there
is
no
quantitative
indication
that
the
fetus
is
more
susceptible
than
the
pregnant
female.

Mutagenicity.
The
data
base
for
mutagenicity
is
considered
adequate
based
on
EPA's
1991
mutagenicity
guidelines
and
indicates
that
p­
tert­
amylphenol
is
not
mutagenic
or
genotoxic.
In
a
submitted
bacterial
study
(
MRID
No.
414384­
01)
and
a
study
identified
in
the
published
literature
(
Zeiger
et
al.
1988),
p­
t­
amylphenol
was
not
mutagenic
to
the
bacteria
in
the
presence
or
absence
of
mammalian
metabolic
activation.
An
assay
using
cultured
mouse
lymphoma
cells
also
proved
negative
(
MRID
No.
415727­
01).
Finally,
a
mouse
micronucleus
test
using
male
and
female
CD­
1
mice
also
was
negative
(
MRID
No.
417108).

Endocrine
Disruption.
4­
t­
Amylphenol
is
listed
on
a
European
list
of
"
Chemicals
purported
to
be
endocrine
disruptors"
(
IEH
2005).
In
the
open
literature
(
Yamasaki
et
al.
2003),
an
increase
in
non­
pregnant
uterine
weight
was
observed
in
rats
following
4­
t­
amylphenol
exposure.
Another
study
(
Soto
et
al.
1995)
suggested
that
4­
t­
amylphenol
may
have
estrogenic
effect.
Wysowski
et
Page
16
of
40
at.
(
1978)
reported
elevated
blood
levels
of
bilirubin
in
children
exposed
to
4­
t­
amylphenol
and
other
phenols
in
disinfectant.
These
studies,
while
not
indicative,
are
suggestive
of
a
basis
for
increased
concern
for
reproductive
and/
or
developmental
effects
due
to
exposure
to
4­
t­
amylphenol.

Soto
et
al.
(
1995)
have
found
p­
t­
amylphenol
to
be
estrogenic
in
the
E­
SCREEN
assay,
which
assesses
the
estrogenicity
of
a
compound
by
measuring
its
proliferative
effect
on
estrogen­
sensitive
cells.
The
cell
number
achieved
by
similar
inocula
of
MCF­
7
cells
(
estrogen­
sensitive
human
breast
cancer
cells)
in
the
absence
of
estrogens
(
negative
control)
and
in
the
presence
of
17­
estradiol
(
positive
control)
is
compared
with
the
number
of
cells
achieved
with
a
range
of
concentrations
of
the
test
chemical.
For
4­
t­
pentylphenol,
a
concentration
of
10
M
was
the
lowest
concentration
needed
for
maximal
cell
yield.
For
the
positive
control
17­
estradiol,
the
lowest
concentration
needed
was
30
pM.
The
relative
proliferative
effect
(
RPE)
is
calculated
as
100
x
(
PE­
1)
of
the
test
compound
divided
by
(
PE­
1)
of
17­
estradiol.
A
value
of
100
indicates
that
the
compound
tested
is
a
full
agonist
of
the
estradiol;
a
value
of
0
indicates
that
the
compound
lacks
estroenicity
at
the
doses
tested.
Intermediate
values
suggest
that
the
compound
is
a
partial
agonist
of
17­
estradiol.
For
4­
t­
pentylphenol,
and
RPE
of
105
was
estimated.

Routledge
and
Sumpter
(
1997)
demonstrated
estrogenic
activity
of
4­
tert­
amylphenol
using
an
estrogen­
inducible
strain
of
yeast
(
Saccharomyces
cerevisiae)
that
expresses
the
human
estrogen
receptor.
Using
the
natural
estrogen
17
 
­
estradiol
for
comparison,
the
data
indicated
that
both
the
position
(
para
>
meta
>
ortho)
and
branching
(
tertiary
>
secondary
=
normal)
of
the
alkyl
group
affect
estrogenicity.
In
this
assay,
4­
t­
amylphenol
was
found
to
be
100,000­
fold
less
potent
than17­
estradiol.

4.2
FQPA
Considerations
Under
the
Food
Quality
Protection
Act
(
FQPA),
P.
L.
104­
170,
which
was
promulgated
in
1996
as
an
amendment
to
the
Federal
Insecticide,
Fungicide,
and
Rodenticide
Act
(
FIFRA)
and
the
Federal
Food,
Drug
and
Cosmetic
Act
(
FFDCA),
the
Agency
was
directed
to
"
ensure
that
there
is
a
reasonable
certainty
that
no
harm
will
result
to
infants
and
children"
from
aggregate
exposure
to
a
pesticide
chemical
residue.
The
law
further
states
that
in
the
case
of
threshold
effects,
for
purposes
of
providing
this
reasonable
certainty
of
no
harm,
"
an
additional
tenfold
margin
of
safety
for
the
pesticide
chemical
residue
and
other
sources
of
exposure
shall
be
applied
for
infants
and
children
to
take
into
account
potential
pre­
and
post­
natal
toxicity
and
completeness
of
the
data
with
respect
to
exposure
and
toxicity
to
infants
and
children.
Notwithstanding
such
requirement
for
an
additional
margin
of
safety,
the
Administrator
may
use
a
different
margin
of
safety
for
the
pesticide
residue
only
if,
on
the
basis
of
reliable
data,
such
margin
will
be
safe
for
infants
and
children."

The
toxicology
data
base
is
not
complete
with
respect
to
assessing
the
increased
susceptibility
to
infants
and
children
as
required
by
FQPA
for
4­
t­
amylphenol.
The
rat
prenatal
developmental
study
showed
no
quantitative
evidence
of
increased
susceptibility
(
i.
e.,
developmental
NOAELs/
LOAELs
were
the
higher
than
those
for
maternal
effects).
However,
there
was
qualitative
evidence
of
increased
susceptibility
(
i.
e.,
fetal
effects
(
skeletal
abnormalities,
decreased
body
weight
gain)
were
considered
to
be
more
severe
than
the
maternal
toxicity
Page
17
of
40
(
reversible
clinical
signs)
observed
at
the
same
dose
level).
In
addition,
there
is
an
absence
of
developmental
toxicity
data
in
the
rabbit,
and
an
absence
of
reproductive
toxicity
data.

In
the
open
literature
(
Yamasaki
et
al.
2003),
an
increase
in
non­
pregnant
uterine
weight
was
observed
in
rats
following
4­
t­
amylphenol
exposure.
Another
study
(
Soto
et
al.
1995)
suggested
that
4­
t­
amylphenol
may
have
estrogenic
effect.
Wysowski
et
at.
(
1978)
reported
elevated
blood
levels
of
bilirubin
in
children
exposed
to
4­
t­
ampyphenol
and
other
phenols
in
disinfectant.
These
studies,
while
not
indicative,
are
suggestive
of
a
basis
for
increased
concern
for
reproductive
and/
or
developmental
effects
due
to
exposure
to
4­
t­
amylphenol.

On
the
basis
of
a
lack
of
guideline
studies,
qualitative
evidence
of
sensitivity
in
the
developmental
toxicity
study,
and
the
suggestive
evidence
in
the
open
literature
of
possible
endocrine
effects,
the
ADTC
has
determined
that
the
FQPA
Safety
Factor
should
be
retained
(
10x)
at
this
time.

4.3
Dose­
Response
Assessment
The
doses
and
toxicological
endpoints
selected
for
various
exposure
scenarios
are
summarized
below.

Table
4.
Toxicological
Endpoints
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
FQPA
SF
and
Endpoint
for
Risk
Assessment
Study
and
Toxicological
Effects
Acute
Dietary
(
Females
13
­
50
years)
NOAEL
=
200
mg/
kg/
day
UF
=
100
DB=
3x
Acute
RfD=
0.67
mg/
kg/
day
FQPA
SF
=
10x
aPAD=
acute
RfD
FQPA
SF
=
0.067
mg/
kg/
day
Developmental
Toxicity
Study
in
Rats
LOAEL
=
500
mg/
kg/
day,
based
on
skeletal
effects
and
decreased
fetal
body
weight
Chronic
Dietary
(
all
populations)
NOAEL
=
50
mg/
kg/
day
UF
=
100
DB=
3x
Chronic
RfD=
0.17
mg/
kg/
day
FQPA
SF
=
10x
cPAD=
chronic
RfD
FQPA
SF
=
0.017
mg/
kg/
day
Developmental
toxicity
study
in
the
rat
LOAEL
=
200
mg/
kg/
day
based
on
clinical
signs
of
toxicity,
decreased
body
weight
and
body
weight
gain,
and
decreased
food
consumption
Incidental
Oral,
Short­
and
Intermediate­
Term
Maternal
Oral
NOAEL
=
50
mg/
kg/
day
Target
MOE
=
3000
(
residential)
(
10x
inter­
and
intra­
species
extrapolation,
10X
FQPA,
3x
database
uncertainty)
Developmental
toxicity
study
in
the
rat
LOAEL
=
200
mg/
kg/
day
based
on
clinical
signs
of
toxicity,
decreased
body
weight
and
body
weight
gain,
and
decreased
food
consumption
Page
18
of
40
Short­,
and
Intermediate
­
Term
Dermal
Dermal
NOAEL
=
25
mg/
kg/
day
for
systemic
effects
Target
MOE
=
1000
(
residential)
(
10x
inter­
and
intraspecies
factors
and
10x
FQPA)
100
(
occupational)
Subchronic
dermal
toxicity
study
in
Rats
Systemic
LOAEL
=
not
identified.
No
systemic
effects
identified
up
to
and
including
25
mg/
kg/
day
(
HDT).

Dermal
LOAEL=
10
mg/
kg/
day
for
dermal
effects
and
irritation.
Dermal
NOAEL=
2.5
mg/
kg/
day
Short­,
Intermediate­,
and
Long­
Term
Inhalation
Oral
NOAEL
=
50
mg/
kg/
day
Target
MOE
=
300
(
occupational)
3000
(
residential)
(
10x
inter­
and
intraspecies
extrapolation,
10x
FQPA,
3x
database
uncertainty,
and
route­
specific
extrapolation
factor)
Developmental
toxicity
study
in
the
rat
LOAEL
=
200
mg/
kg/
day
based
on
clinical
signs
of
toxicity,
decreased
body
weight
and
body
weight
gain,
and
decreased
food
consumption.

Cancer
No
cancer
data
available
for
4­
t­
amylphenol
Database
Uncertainty
Factor.
For
oral
and
inhalation
risk
assessments,
the
ADTC
applied
an
additional
uncertainty
factor
of
3x
at
this
time,
due
to
the
number
and
significance
of
the
data
gaps
for
conduct
of
these
risk
assessments.
A
3x
factor
was
not
needed
for
the
dermal
route
as
an
acceptable
route­
specific
study
was
available.

4.4
Endocrine
Disruption
The
Food
Quality
Protection
Act
(
FQPA;
1996)
requires
that
EPA
develop
a
screening
program
to
determine
whether
certain
substances
(
including
all
pesticides
and
inerts)
"
may
have
an
effect
in
humans
that
is
similar
to
an
effect
produced
by
a
naturally
occurring
estrogen,
or
such
other
endocrine
effect...."
Following
the
recommendations
of
its
Endocrine
Disruptor
Screening
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).

When
the
appropriate
screening
and/
or
testing
protocols
being
considered
under
the
Agency's
EDSP
have
been
developed,
4­
t­
amylphenol
and
its
potassium
and
sodium
salts
may
be
subjected
to
additional
screening
and/
or
testing
to
better
characterize
effects
related
to
endocrine
disruption.
Page
19
of
40
As
noted
previously,
the
available
data
suggest
that
4­
t­
amylphenol
has
endocrine
disrupter
capabilities
(
uterotrophic
and
estrogenic
effects)
and
increased
bilirubin
production
in
babies.

5.0
EXPOSURE
ASSESSMENT
AND
CHARACTERIZATION
Dietary
exposure
to
4­
t­
amylphenol
can
occur
from
use
as
a
disinfectant
and
food­
contact
sanitizer.
Residential
exposure
can
occur
from
4­
t­
amylphenol­
containing
products,
such
as
hard
surface
disinfectants.
Postapplication
exposure
can
occur
in
adults
and
children
from
dermal
contact
with
treated
textiles
and
diapers,
as
well
as
in
children
from
hand­
to­
mouth
incidental
oral
exposure
from
treated
surfaces.
Occupational
exposure
to
4­
t­
amylphenol
can
occur
from
mixing/
loading/
application
activities
in
various
use
sites,
including
agricultural
premises,
food
handling,
commercial/
institutional/
industrial
premises
and
medical
premises.

5.1
Summary
of
Registered
Uses
4­
t­
Amylphenol,
and
salts
(
potassium
and
sodium)
are
active
ingredients
in
disinfectant,
food­
contact
sanitizer
and
deodorizer
products
used
in
agricultural,
food
handling,
commercial/
institutional/
industrial,
residential
and
public
access,
and
medical
settings,
primarily
used
on
hard,
non­
porous
surfaces.
Examples
of
registered
uses
for
4­
tert­
amylphenol
and
salts
include
application
to
hard
surfaces
(
e.
g.,
walls,
floors,
tables,
fixtures),
textiles
(
e.
g.,
clothing,
diapers,
mattresses,
bedding),
carpets,
medical
instruments,
and
agricultural
equipment.
Additionally,
there
are
registered
uses
for
fogging
in
occupational
settings
and
air
deodorization
in
both
occupational
and
residential
settings.
Concentrations
of
4­
tert­
amylphenol
and
salts
in
products
range
from
0.0027%
to
10%.
The
products
are
formulated
as
soluble
concentrates,
ready­
to­
use
liquid
solutions,
pressurized
sprays,
and
impregnated
wipes.
The
application
rates
used
in
this
assessment
were
the
maximum
application
rates
as
recommended
on
the
product
labels.

5.2
Dietary
Exposure
and
Risk
Estimates
of
dietary
risk
are
based
upon
the
detailed
analysis
in
the
Dietary
Exposure
Assessment
memorandum
(
memo
from
R.
Quick
to
K.
Swift,
September
2005,
D316295)
and
are
summarized
here
for
completeness.
4­
t­
Amylphenol
and
its
potassium
salt
are
antimicrobials
that
can
be
used
as
disinfectants
or
sanitizers
on
counter
tops,
tables,
refrigerators,
on
animal
premises;
and
in
mushroom
premises.
There
are
other
registered
uses
for
these
chemicals
that
include
but
are
not
limited
to
odor
elimination
in
rooms,
beauty
parlors
and
medical
premises.
There
are
32
registered
products
that
contain
4­
t­
amylphenol
or
its
potassium
and
sodium
salts
as
active
ingredients
that
may
result
in
dietary
exposure.
4­
t­
Amylphenol
(
also
known
as
phenol,
4­
1,1­
dimethylpropyl)
(
CAS
No.
80­
46­
6)
has
a
tolerance
exception
in
40CFR
180.940
(
c)
as
a
food­
contact
sanitizer
for
use
in
food­
processing
equipment
and
utensils
with
a
not
to
exceed
limit
of
80
ppm.

The
use
of
antimicrobial
chemicals
on
food
or
feed
contact
surfaces,
agricultural
commodities,
in
animal
premises
and
poultry
premises
including
hatcheries
and
application
to
Page
20
of
40
food­
grade
eggs
may
result
in
pesticide
residues
in
human
food.
The
Agency
must
determine
the
risk
to
human
health
that
may
occur
from
exposure
to
these
chemicals.

Refrigerators
counter
tops,
sinks
and
stoves
are
use
sites
on
registered
labels.
These
surfaces
that
have
been
treated
with
the
4­
t­
amylphenol
products
may
bear
small
residues
of
the
4­
t­
amylphenol
products
after
rinsing
with
potable
water;
i.
e.,
rinsing
with
potable
water
may
not
remove
all
residues
deposited
on
the
treated
surfaces
from
the
proposed
uses.
Residues
from
treated
surfaces
can
migrate
to
food
coming
into
contact
with
the
treated
and
rinsed
surfaces
and
can
be
ingested
by
humans.

In
the
absence
of
residue
data
for
residues
of
4­
t­
amyphenol
on
treated
food
contact
surfaces,
the
Agency
estimated
residue
levels
that
may
occur
in
food
from
the
application
rates
on
food
contact
surfaces.
To
estimate
the
Estimated
Daily
Intake
(
EDI),
the
Agency
has
used
an
FDA
model.
The
maximum
ingredient
percentage
for
4­
t­
amylphenol
in
food
handling
establishments
from
the
various
labeled
ready­
to­
use
products
is
0.054
%
a.
i
(
540
ppm).
The
Agency
estimates
that
use
of
this
product
results
in
4­
t­
amylphenol
food
residues
of
340
ppb
(
µ
g/
kg).
The
Agency
assumed
that
food
can
contact
2000
cm2
of
treated
surfaces,
and
that
10%
of
the
pesticide
migrates
to
food
based
on
the
Agency
Residential
SOPs.
The
use
of
the
10%
transfer
rate
instead
of
the
use
of
a
100%
transfer
rate
that
is
used
in
the
FDA
Sanitizer
Solution
Guidelines
requires
the
submission
of
confirmatory
data
to
establish
the
reliability
of
the
use
of
the10%
transfer
rate.
These
daily
estimates
were
conservatively
used
to
assess
both
acute
and
chronic
dietary
risks,
which
are
shown
below
in
Table
5.

Table
5.
Summary
of
Dietary
Exposure
and
Risk
for
4­
t­
amylphenol
Acute
Dietary
Chronic
Dietary
Population
Subgroup
Dietary
Exposure
(
mg/
kg/
day)
a
%
aPAD
b
Dietary
Exposure
(
mg/
kg/
day)
a
%
cPAD
b
adult
male
0.0015
NA
0.0015
9
females
(
13­
50
years)
0.0018
2.7
0.0018
10.6
infants/
children
0.0072
NA
0.0072
42
NA=
not
applicable
a­­
acute
and
chronic
exposure
analysis
based
on
body
weights
of
70
kg,
60
kg,
and
15
kg
for
adult
males,
females
and
children,
respectively.
b­­
%
PAD
=
dietary
exposure
(
mg/
kg/
day)
/
aPAD
or
cPAD,
where
aPAD=
0.067
mg/
kg/
day
for
females
of
child
bearing
age;
and
cPAD=
0.017
mg/
kg/
day
for
all
populations
Dietary
exposures
from
general
agricultural
premise
use,
poultry
hatcheries,
mushroom
houses
and
greenhouse
and
hydroponic
uses
are
expected
to
be
much
lower
than
the
dietary
exposures
resulting
from
the
surface
disinfectant
and
sanitizing
uses.

Agricultural
premise
uses
involve
the
application
of
a
pesticide
chemical
to
the
hard
surface
interior
surfaces
of
the
interior
of
barns
and
poultry
houses.
These
uses
involve
application
Page
21
of
40
to
the
physical
structure
of
the
premises
(
including
floors
and
walls)
and
also
include,
but
not
limited
to,
watering
troughs,
feed
troughs,
animal
halters,
ropes
and
forks.

Poultry
hatcheries
are
not
used
in
the
production
of
eggs
for
food­
grade
eggs
for
human
consumption.
Hatchery
eggs
are
used
for
the
production
of
chicks.
Sanitizer
chemicals
could
penetrate
the
egg
shell
and
become
a
residue
in
the
developing
chick.
Any
residues
that
did
penetrate
the
egg
shell
and
occur
in
the
chick
would
not
be
expected
to
be
detectable
in
birds
that
are
ready
for
consumption
because
of
growth
dilution
in
the
growing
birds.
The
use
of
p­
tertiary
amylphenol
products
in
poultry
hatcheries
appears
to
be
a
non­
food
use.

4­
t­
Amylphenol
is
used
for
cleaning
and
sanitizing
non­
food
contact
surfaces
between
crops
in
mushrooms.
Surfaces
that
are
treated
include
tanks,
air
conditioners,
air
ducts,
fans
and
breezeways,
compost
wharf,
concreted
surfaces,
inside
and
outside
walls
of
mushroom
houses,
lofts,
floors,
spawning
machines,
tampers,
casing
rings,
storage
sheds
and
track
alleys
before
spawning.
Thus,
the
use
of
4­
t­
amylphenol
products
in
mushroom
houses
appears
to
be
a
non­
food
use.

Food
commodities
can
be
grown
in
greenhouses
and
on
hydroponic
farms.
The
food
commodities
can
be
grown
in
a
growing
media
or
hydroponically
in
water.
There
is
a
label
restriction
against
application
to
crop,
soil
or
growing
media
in
which
a
crop
grows
or
will
be
grown.
There
is
also
a
label
instruction
that
requires
a
potable
water
rinse
before
treated
surfaces
contact
the
crop
or
the
substrate
in
which
the
crop
is
or
will
be
grown.
A
potable
water
rinse
for
treated
surfaces
will
likely
remove
a
part,
but
not
all
of
the
residues
from
treated
surfaces.
The
growing
structures
could
be
made
of
wood,
plastic,
concrete
or
metal.
The
greatest
potential
for
residues
adhering
to
treated
surfaces
would
be
expected
to
be
from
the
use
of
wood
structures.
Wood
is
porous
and
residues
would
likely
be
absorbed
into
the
treated
surfaces.
This
would
also
be
true
to
a
lesser
extent
on
concrete
surfaces.
Metal
surfaces
would
not
be
porous
and
rinsing
well
or
scrubbing
would
likely
remove
most
or
all
pesticide
residues.

5.3
Drinking
Water
Exposure
and
Risk
There
are
no
currently
registered
outdoor
uses
of
4­
t­
amylphenol
and
its
salts
that
are
being
supported
by
the
registrant.
The
potential
outdoor
uses,
wood
protection
to
treat
unseasoned
forest
products,
and
use
in
potable
human
drinking
water
systems
are
apparently
no
longer
supported
by
any
registrant.
4­
t­
Amylphenol's
use
as
a
general
disinfectant
allows
for
the
possibility
of
ground
and
surface
water
contamination.
It
has
been
found
in
an
effluent
sample
from
a
municipal
waste
water
treatment
plant.
However,
the
estimated
value
for
biodegradation
indicates
it
may
biodegrade
linearly
within
days
in
the
aquatic
environment,
although
ultimate
biodegradation
(
mineralization)
may
take
months.
It
is
also
volatile
based
on
its
vapor
pressure
of
0.00116
mmHg,
and
has
a
moderate
to
slight
mobility
in
soils
based
on
its
estimated
Koc
value
of
3799.
The
sodium
and
potassium
salts
of
4­
t­
amylphenol
are
also
slightly
to
moderately
mobile
in
soils,
and
are
estimated
to
biodegrade
within
days
to
weeks.
Because
of
the
possibility
of
biodegradation
in
water
and
soils,
4­
t­
amylphenol
and
its
salts
are
not
likely
to
contaminate
surface
and
ground
waters.
Thus,
a
drinking
water
assessment
was
not
conducted
for
these
chemicals.
Page
22
of
40
5.4
Residential
Exposure/
Risk
Pathway
Details
of
the
residential
exposure
assessment
can
be
found
within
the
companion
memorandum
(
memorandum
from
S.
Mostaghimi,
September
2005).
A
summary
of
the
residential
assessment
is
presented
below.

5.4.1
Residential
Handler
Exposure
Scenarios
4­
t­
Amylphenol
is
a
disinfectant,
sanitizer
and
deodorizer,
that
is
used
in
agricultural,
food
handling,
commercial/
institutional/
industrial,
residential
and
medical
settings.
It
is
used
as
a
hard
surface
disinfectant
(
e.
g.,
walls,
floors,
tables,
fixtures),
textiles
(
e.
g.,
clothing,
diapers,
mattresses,
bedding),
carpets,
medical
instruments
and
agricultural
equipment.
The
following
representative
residential
handler
scenarios
were
evaluated:

(
1)
mopping
hard
surfaces,
(
2)
wiping
hard
surfaces,
(
3)
using
trigger
pump
equipment
to
treat
hard
surfaces
and/
or
textiles,
and
(
4)
application
to
air
using
an
aerosol
spray
can
4­
t­
amylphenol
and
salt
products
are
widely
used
disinfectants
and
have
a
large
number
of
use
patterns
that
are
difficult
to
completely
capture
in
this
assessment.
As
such,
AD
has
selected
representative
scenarios
for
each
use
site
that
are
believed
to
be
representative
of
the
vast
majority
of
4­
t­
amylphenol
and
salt
uses,
based
on
end­
use
product
application
methods
and
use
amounts.

Exposure
Data
and
Assumptions
There
are
no
chemical­
specific
exposure
data
to
assess
paint
applications
with
a
brush,
roller,
airless
sprayer
or
aerosol
can.
However,
surrogate
data
are
available
for
mopping,
wiping,
trigger
pump
spray
and
aerosol
can
application
methods.
Dermal
and
inhalation
exposures
were
assessed
for
mopping
and
wiping
using
proprietary
Chemical
Manufacturers
Association
(
CMA)
data
(
CMA
1992,
USEPA
1999).
These
data
are
based
on
individuals
mopping
floors
and
receiving
exposure
via
contact
with
the
mop
or
with
the
bucket,
or
using
a
finger
pump
sprayer
to
apply
the
product
and
then
wipe
the
surfaces
with
a
paper
towel.
Dermal
and
inhalation
exposures
were
assessed
for
trigger
pump
spray
and
aerosol
application
methods
using
PHED
Version
1.1
values
found
in
the
Residential
Exposure
SOPs
(
U.
S.
EPA,
1997a,
2001).
The
surrogate
exposure
data
in
PHED
are
based
on
test
subjects
applying
an
aerosol
insecticide
to
baseboards
in
kitchens.
The
dermal
and
inhalation
exposures
from
these
techniques
have
been
normalized
by
the
amount
of
active
ingredient
handled
and
reported
as
unit
exposures
(
UE)
expressed
as
mg/
lb
ai
handled.

In
addition,
product
label
maximum
application
rates,
related
use
information,
and
Agency
standard
values
were
used
to
assess
residential
handler
exposures.
For
example,
it
was
assumed
that
one
gallon
of
diluted
solution
is
used
for
mopping
floors,
while
0.5
liters
(
0.13
gallons)
are
used
in
the
wiping
and
trigger
pump
spray
scenario.
For
aerosol
can
spray,
it
was
assumed
that
Page
23
of
40
one
16
oz
can
of
product
is
used
in
a
day.
The
residential
handler
scenarios
are
assumed
to
be
of
short­
and
intermediate­
term
duration
(
1­
30
days
and
1­
6
months)

Risk
Characterization
A
summary
of
the
residential
handler
exposures
and
risk
are
presented
on
Table
6.
The
non­
cancer
risk
estimates
are
expressed
in
terms
of
the
MOE.
For
residential
handlers
that
handle
products
containing
4­
t­
amylphenol
and
its
salts,
short­
term,
and
intermediate­
term
MOEs
were
above
the
target
MOEs
(
i.
e.,
 
>
1000
for
dermal
and
>
3000
for
inhalation)
and
thus,
do
not
exceed
the
Agency's
level
of
concern
for
any
of
the
residential
handler
scenarios
evaluated.

Table
6
Estimates
of
Exposures
and
Risks
to
Residential
Handlers
of
4­
t­
Amylphenol
and
salts
(
Short­
and
Intermediate­
Duration)

Scenario
Dermal
Dose
(
mg/
kg/
day)
a
Inhalation
Dose
(
mg/
kg/
day)
b
Dermal
MOEc
(
Target
MOE>
1000)
Inhalation
MOEd
(
Target
MOE>
3000)

(
1)
Mopping
0.00128
4.25x10­
5
20,000
1,200,000
(
2)
Wiping
0.00666
1.56x10­
4
3,800
320,000
(
3)
Trigger
Pump
Spray
0.00198
2.16x10­
5
13,000
2,300,000
(
4)
Aerosol
Spray
0.00233
2.54x10­
5
11,000
2,000,000
a
Dermal
Dose
(
mg/
kg/
day)
=
[
Unit
Dermal
Exposure
(
mg/
lb
ai)
*
Use
Rate
(
lb
ai/
lb
product
or
lb
ai/
gal
product)
*
Amount
Handled
per
Day
(
lb
product/
day)]
/
Body
Weight
(
kg).
b
Inhalation
Dose
(
mg/
kg/
day)
=
[
Unit
Inhalation
Exposure
(
mg/
lb
ai)
*
Use
Rate
(
lb
ai/
lb
product
or
lb
ai/
gal
product)
*
Amount
Handled
per
Day
(
lb
product/
day)*
inhalation
absorption
(
1.0)]
/
Body
Weight
(
kg)
c
Dermal
MOE
=
Dermal
NOAEL
(
mg/
kg/
day)
/
Dermal
Dose
(
mg/
kg/
day).
Where
the
NOAEL
is
25
mg/
kg/
day
from
the
subchronic
rat
dermal
toxicity
study.
d
Inhalation
MOE
=
Inhalation
NOAEL
(
mg/
kg/
day)
/
Inhalation
Dose
(
mg/
kg/
day).
Where
the
inhalation
NOAEL
of
50
mg/
kg/
day
is
from
an
oral
rat
developmental
study.
In
the
absence
of
data,
inhalation
absorption
is
assumed
to
be
equivalent
to
oral
absorption
5.4.2
Postapplication
Residential
Exposure
Residential
postapplication
exposures
result
when
bystanders
(
adults
and
children)
come
in
contact
with
4­
t­
amylphenol
and
its
salts
in
areas
where
pesticide­
treated
end­
use
products
have
recently
been
applied
(
e.
g.,
treated
hard
surfaces/
floors),
or
when
children
incidentally
ingest
the
pesticide
residues
through
mouthing
the
treated
end
products/
treated
articles
(
i.
e.,
hand­
to­
mouth
or
object­
to­
mouth
contact).

For
the
purposes
of
this
screening
level
assessment,
postapplication
scenarios
have
been
developed
that
encompass
multiple
products,
but
still
represent
a
high
end
exposure
scenario
for
all
products
represented.
Representative
postapplication
scenarios
assessed
include:
Page
24
of
40
°
contacting
treated
hard
surfaces/
floors
(
dermal
and
incidental
oral
exposure
to
children),
°
wearing
treated
clothing
(
dermal
exposure
to
adults
and
children),
°
wearing
diapers
treated
with
a
trigger­
pump
spray
(
dermal
exposure
to
children),
°
mouthing
treated
textiles
such
as
clothing
and
blankets
(
incidental
oral
exposure
to
children),
and
°
postapplication/
bystander
inhalation
exposures
from
use
of
disinfecting/
deodorizing
products
(
vapor
exposure
to
adults
and
children).

Exposure
Data
and
Assumptions
Typically,
most
products
used
in
a
residential
setting
result
in
exposures
occurring
over
a
short­
term
time
duration
(
1
 
30
days).
If
the
products
are
used
on
a
routine
basis
(
i.
e.,
once
a
week)
and
the
active
ingredient
has
a
long
indoor
half­
life,
exposures
may
occur
over
an
intermediate­
term
time
duration
(
30
days
 
6
months).
At
this
time,
AD
does
not
have
residue
dissipation
data
or
reliable
use
pattern
data,
including
the
frequency
and
duration
of
use
of
antimicrobial
products
in
the
residential
setting.
Even
though
AD
does
not
believe
that
the
use
patterns
of
many
residential
products
result
in
intermediate­
term
exposure,
they
are
assessed
to
provide
an
upper
bound
estimate
of
exposure.
AD
does
believe,
however,
that
intermediate­
term
exposure
to
children
may
occur
in
day
care
centers
where
disinfecting
products
are
used
more
frequently.

A
number
of
conservative
assumptions
were
used
in
assessing
postapplication
risks
including
maximum
application
rate
from
the
label.
In
addition
quantities
handled/
treated
were
estimated
based
on
information
from
various
sources,
including
the
Draft
Standard
Operating
Procedures
(
SOPs)
for
Residential
Exposure
Assessments
(
USEPA
2000,
2001)
and
the
AD
Draft
Residential
SOP
use
table.
In
certain
cases,
no
standard
values
were
available
for
some
scenarios.
Assumptions
for
these
scenarios
were
based
on
AD
estimates
and
could
be
further
refined
from
input
from
affected
sectors.
In
the
absence
of
data,
for
both
the
textile
and
diaper
scenarios,
it
was
assumed
that
either
100%
or
5%
of
4­
t­
amylphenol
could
transfer
and
be
available
for
dermal
contact.
The
Agency
will
require
data
to
confirm
the
actual
transfer
factor
of
4­
t­
amylphenol
No
postapplication
air
concentration
data
have
been
submitted
for
4­
t­
amylphenol
to
determine
potential
vapor
inhalation
risk.
Therefore,
the
Multi­
Chamber
Concentration
and
Exposure
Model
(
MCCEM
v1.2)
was
used
to
present
a
screening­
level
estimate
of
the
potential
inhalation
risk
to
adults
and
children
for
the
air
deodorizer
use.
MCCEM
estimates
average
and
peak
indoor
air
concentrations
of
chemicals
released
from
products
or
materials
in
houses,
apartments,
townhouses,
or
other
residences.
The
data
libraries
in
MCCEM
contain
information
about
residential
settings.
MCCEM
estimates
inhalation
exposures
to
chemicals,
calculated
as
single
day
doses,
chronic
average
daily
doses,
or
lifetime
average
daily
doses.
(
All
dose
estimates
are
potential
doses;
they
do
not
account
for
actual
absorption
into
the
body.)

Risk
Characterization
A
summary
of
the
residential
postapplication
exposures
and
risks
are
presented
on
Table
7.
The
non­
cancer
risk
estimates
are
expressed
in
terms
of
the
MOE.
The
target
MOEs
are
>
1000
Page
25
of
40
for
dermal
exposures,
and
>
3000
for
incidental
oral
and
inhalation
exposures.

Dermal
Risks.
The
child
short­
and
intermediate­
term
dermal
MOEs
for
contact
following
hard
surface
disinfection
is
above
the
target
MOE
of
1,000
for
residential
settings
(
MOE
=
3,700)
and
slightly
below
the
MOE
for
daycare
centers
(
MOE
=
940).
The
short­
and
intermediate­
term
MOEs
for
dermal
contact
with
treated
clothing
is
of
concern
for
young
children
(
MOEs
are
<
1
assuming
a
100%
transfer
factor;
MOE=
17
assuming
a
5%
transfer
factor).
For
adults,
the
dermal
MOE
is
below
the
target
MOE
of
1,000
using
a
100%
transfer
factor
(
MOE
=
140)
and
above
the
MOE
using
the
5%
transfer
factor
(
MOE
=
2,700).
The
dermal
MOE
for
a
children
wearing
treated
diapers
is
only
of
concern
(
MOE=
59)
using
a
transfer
factor
of
100%,
but
it
not
of
concern
when
using
a
transfer
factor
of
5%.
The
Agency
requires
confirmatory
data
for
a
4­
t­
amylphenol
transfer
factor
from
clothing
and
diapers.
In
addition,
it
should
be
noted
that
4­
t­
amylphenol
caused
dermal
irritant
effects
following
repeated
dermal
exposure,
and
may
also
be
a
potential
dermal
sensitizer.
The
Agency
intends
to
consider
these
effects
in
the
labeling
of
pesticide
products
containing
4­
t­
amylphenol,
and
request
additional
dermal
toxicity
data
on
the
diluted
end­
use
formulated
product.

Incidental
Oral
Risks.
The
short­
and
intermediate­
term
incidental
oral
MOEs
following
hard
surface
disinfection
are
above
the
target
MOE
of
3,000
for
residential
settings
(
MOE
=
61,000)
and
daycare
centers
(
MOE
=
15,000),
and
thus
are
not
of
concern.
However,
the
oral
MOE
for
children
mouthing
treated
textiles
exceeds
the
Agency's
level
of
concern
(
MOE=
650
compared
to
target
MOE>
3000).

Inhalation
Risks.
For
both
adults
and
children,
the
calculated
inhalation
MOEs
are
greater
than
the
target
MOE
of
3,000
(
MOE=
27,000
and
7,500,
respectively),
for
inhalation
exposures
following
use
of
an
air
deodorizer.

Table
7
Summary
of
Short­
and
Intermediate­
Term
Residential
Postapplication
Exposures
and
Risks
Scenario
Dose
a
(
mg/
kg/
day)
MOEb
(
Target
MOE>
1000
dermal;
>
3000
oral
and
inhalation)
Dermal
Exposure
Residential
Setting
0.0067
3,700
Hard
surface
Disinfection
Daycare
center
0.0267
940
Adults
0.0092
(
5%
transfer)
0.185
(
100%
transfer)
2,700
140
Treated
clothing
Children
1.45
(
5%
transfer)
28.9
(
100%
transfer)
17
<
1
Treated
Diapers
Children
0.0212
(
5%
transfer)
0.424
(
100%
transfer)
1,200
59
Incidental
Oral
Exposure
Residential
Setting
0.000817
61,000
Hard
surface
Disinfection
Daycare
center
0.00155
32,000
Treated
clothing
Children
650
Inhalation
Exposure
Page
26
of
40
Table
7
Summary
of
Short­
and
Intermediate­
Term
Residential
Postapplication
Exposures
and
Risks
Scenario
Dose
a
(
mg/
kg/
day)
MOEb
(
Target
MOE>
1000
dermal;
>
3000
oral
and
inhalation)
Adults
0.00186
27,000
Air
Deodorizer
Children
0.00666
7,500
a
Dose
calculations
for
each
scenario
above
are
outlined
in
the
attached
Occupational/
Residential
Assessment
(
memo
from
S.
Mostaghimi,
May
2005).
b
MOE=
NOAEL
(
mg/
kg/
day)
/
PDR
(
mg/
kg/
day).
Oral
and
inhalation
NOAEL
is
50
mg/
kg/
day;
dermal
NOAEL
is
25
mg/
kg/
day
6.0
AGGREGATE
RISK
ASSESSMENTS
AND
RISK
CHARACTERIZATION
In
order
for
a
pesticide
registration
to
continue,
it
must
be
shown
that
the
use
does
not
result
in
"
unreasonable
adverse
effects
on
the
environment".
Section
2
(
bb)
of
FIFRA
defines
this
term
to
include
"
a
human
dietary
risk
from
residues
that
result
from
a
use
of
a
pesticide
in
or
on
any
food
inconsistent
with
standard
under
section
408..."
of
FFDCA.
As
mandated
by
the
FQPA
amendments
to
FIFRA
and
the
Federal
Food,
Drug
and
Cosmetic
Act
(
FFDCA),
the
Agency
must
consider
total
aggregate
exposure
from
food,
drinking
water
and
residential
sources
of
exposure
to
4­
t­
amylphenol.
Aggregate
exposure
is
the
total
exposure
to
a
single
chemical
(
or
its
residues)
that
may
occur
from
dietary
(
i.
e.,
food
and
drinking
water),
residential,
and
other
non­
occupational
sources,
and
from
plausible
exposure
routes
(
oral,
dermal,
and
inhalation).

Typically,
aggregate
risk
assessment
are
conducted
for
acute
(
1
day),
short­
term
(
1­
30
days),
intermediate­
term
(
1­
6
months)
and
chronic
(
6
months
to
lifetime)
exposures.
However,
acute
and
chronic
aggregate
assessments
were
not
conducted
because
there
are
no
significant
impacts
to
drinking
water
sources,
nor
are
there
long­
term
residential
uses.
Thus,
only
short­
and
intermediate­
term
aggregate
assessments
were
conducted.
Oral
and
inhalation
exposure
and
risk
estimates
were
combined
for
the
aggregate
risk
assessment
because
these
endpoints
are
based
on
the
same
toxicity
study
(
oral
developmental
study)
and
effects
of
concern
(
clinical
signs
and
changes
in
body
weight
and
food
consumption).
Dermal
exposures
were
not
aggregated
with
the
oral
or
inhalation
exposures
due
to
different
toxicological
endpoints
for
oral
(
clinical
signs
and
body
weight
changes),
and
dermal
(
no
systemic
effects
at
the
highest
dose
tested).

In
performing
aggregate
exposure
and
risk
assessments,
the
Office
of
Pesticide
Programs
has
published
guidance
outlining
the
necessary
steps
to
perform
such
assessments
(
General
Principles
for
Performing
Aggregate
Exposure
and
Risk
Assessments,
November
28,
2001;
available
at
http://
www.
epa.
gov/
pesticides/
trac/
science/
aggregate.
pdf
).
Steps
for
deciding
whether
to
perform
aggregate
exposure
and
risk
assessments
are
listed,
which
include:
identification
of
toxicological
endpoints
for
each
exposure
route
and
duration;
identification
of
potential
exposures
for
each
pathway
(
food,
water,
and/
or
residential);
reconciliation
of
durations
and
pathways
of
exposure
with
durations
and
pathways
of
health
effects;
determination
of
which
possible
residential
exposure
scenarios
are
likely
to
occur
together
within
a
given
time
frame;
Page
27
of
40
determination
of
magnitude
and
duration
of
exposure
for
all
exposure
combinations;
determination
of
the
appropriate
technique
(
deterministic
or
probabilistic)
for
exposure
assessment;
and
determination
of
the
appropriate
risk
metric
to
estimate
aggregate
risk.

6.1
Short­
and
Intermediate­
Term
Aggregate
Risk
Aggregate
short
and
intermediate
term
risk
assessments
are
designed
to
provide
estimates
of
risk
likely
to
result
from
exposures
to
the
pesticide
or
pesticide
residues
in
food,
water,
and
from
residential
(
or
other
non­
occupational)
pesticide
uses.
Short­
and
intermediate­
term
aggregate
risks
are
considered
together
because
the
exposure
and
toxicity
endpoints
are
identical
for
incidental
oral,
and
inhalation
residential
exposures
for
both
durations.
For
children,
the
short­
and
intermediate­
term
aggregate
assessment
includes
average
dietary
exposure
(
food)
and
estimated
incidental
oral
exposures
to
children
from
residential
uses
such
as
hard
surface
disinfection.
In
addition,
inhalation
exposure
from
the
postapplication
of
an
air
deodorizer
use
was
aggregated
with
the
oral
exposures
since
the
toxicity
endpoint
is
the
same.
For
adults,
the
aggregate
assessment
includes
dietary
(
oral)
and
residential
inhalation
exposures
from
wiping
a
hard
surface
disinfectant,
in
addition
to
postapplication
inhalation
exposure
from
the
air
deodorizer.

Aggregate
risks
were
calculated
using
the
total
MOE
approach
outlined
in
OPP
guidance
for
aggregate
risk
assessment
(
August
1,
1999,
Updated
"
Interim
Guidance
for
Incorporating
Drinking
Water
Exposure
into
Aggregate
Risk
Assessments").
The
assumptions
and
equations
are
presented
in
the
footnotes
on
Table
8.

Oral
and
Inhalation
Aggregate
Risks.
Table
8
presents
a
summary
of
the
short­
and
intermediate­
term
aggregate
risk
MOEs.
The
aggregate
oral
and
inhalation
risks
are
not
of
concern
for
adults,
as
the
total
aggregate
MOE
is
13,000
which
is
greater
than
the
target
of
3,000.
For
children,
the
aggregate
risk
estimates
are
also
above
the
target
MOE
of
3000
(
MOE=
3,200)
and
thus
are
not
of
concern.
It
should
be
noted
that
several
conservative
assumptions
were
used
in
this
assessment.
As
noted
previously,
incidental
oral
exposure
to
treated
textiles
are
not
included
in
the
aggregate
assessment
because
the
oral
MOE
is
already
of
concern
(
MOE=
650
vs
target
>
3000).

Dermal
Risk
Results.
A
dermal
aggregate
assessment
was
not
conducted
because
the
toxicity
effects
for
the
dermal
exposure
route
are
not
the
same
as
the
oral/
inhalation
exposure
route.
However,
as
shown
previously
on
Table
7,
short­
and
intermediate
dermal
risks
are
already
of
concern
for
residents
for
the
treated
textile
and
diaper
use.

Table
8
Summary
of
Short­
and
Intermediate­
Term
Aggregate
Risk
Estimates
Dose
a
(
mg/
kg/
day)
Total
MOEb
(
Target
MOE>
3000)
Exposure
Scenario
Child
Adult
Child
Adult
Oral
Exposure
Dietary
Exposure
0.0072
0.0018
(
a)
6940
(
c)
28,000
(
c)
Hard
surface
Disinfection
­­
Daycare
center
0.00155
NA
32,000
NA
Page
28
of
40
Table
8
Summary
of
Short­
and
Intermediate­
Term
Aggregate
Risk
Estimates
Dose
a
(
mg/
kg/
day)
Total
MOEb
(
Target
MOE>
3000)
Exposure
Scenario
Child
Adult
Child
Adult
Inhalation
Exposure
Handler
of
hard
surface
disinfectant­­
wiping
NA
0.000156
NA
320,000
Air
Deodorizer
0.00666
0.00186
7,500
27,000
Total
Aggregate
Dose
and
MOE
0.0154
0.00316
3,240
13,000
NA=
Not
applicable
(
a)
Chronic
dietary
exposure
for
females
13­
50
years.
(
b)
MOE
=
NOAEL
(
mg/
kg/
day)
/
potential
dose
rate
(
mg/
kg/
day)
[
Where
short­
and
intermediate­
term
oral
NOAEL
=
50
mg/
kg/
day].
Target
MOE
=
3,000.
(
c)
Risk
estimates
are
equivalent
to
percent
of
the
PAD
of
42%
for
child
and
10.6%
for
adults.

6.2
Long­
Term
Aggregate
Risk
A
long­
term
aggregate
assessment
was
not
conducted
because
the
only
long­
term
residential
use
(
diaper
use)
results
in
dermal
exposure,
which
has
a
different
toxicological
effect
than
the
chronic
dietary
oral
exposure.

7.0
CUMULATIVE
EXPOSURE
AND
RISK
Another
standard
of
section
408
of
the
FFDCA
which
must
be
considered
in
making
an
unreasonable
adverse
effect
determination
is
that
the
Agency
considers
"
available
information"
concerning
the
cumulative
effects
of
a
particular
pesticide's
residues
and
"
other
substances
that
have
a
common
mechanism
of
toxicity."

For
the
purposes
of
this
tolerance
action,
therefore,
EPA
has
not
assumed
that
4­
t­
amylphenol
and
its
potassium
and
sodium
salts
have
a
common
mechanism
of
toxicity
with
other
substances.
For
information
regarding
EPA's
efforts
to
determine
which
chemicals
have
a
common
mechanism
of
toxicity
and
to
evaluate
the
cumulative
effects
of
such
chemicals,
see
the
policy
statements
released
by
EPA's
Office
of
Pesticide
Programs
concerning
common
mechanism
determinations
and
procedures
for
cumulating
effects
from
substances
found
to
have
a
common
mechanism
on
EPA's
website
at
http://
www.
epa.
gov/
pesticides/
cumulative/.

8.0
OCCUPATIONAL
EXPOSURE
AND
RISK
AD
has
assessed
the
exposures
and
risks
to
occupational
workers
that
handle
4­
t­
amylphenol
(
memorandum
from
S.
Mostaghimi,
September
2005).
This
section
summarizes
the
results
of
the
occupational
exposure
assessment.

Based
on
examination
of
product
labels
describing
uses
for
the
product,
it
has
been
determined
that
exposure
to
handlers
can
occur
in
a
variety
of
occupational
settings.
Additionally,
Page
29
of
40
postapplication
exposures
are
likely
to
occur
in
these
settings.
The
representative
scenarios
selected
by
AD
for
assessment
were
evaluated
using
maximum
application
rates
as
recommended
on
the
product
labels
for
4­
t­
amylphenol.

Occupational
Handlers.
The
Agency
has
determined
that
there
is
potential
for
dermal
and
inhalation
worker
exposure
to
4­
t­
amylphenol
at
various
use
sites
including
agricultural
premises,
food
handling,
commercial/
institutional/
industrial
premises,
and
medical
premises.
The
occupational
exposure
scenarios,
and
estimated
risks
are
presented
on
Table
9.

To
assess
the
handler
risks,
AD
used
surrogate
unit
exposure
data
from
both
the
proprietary
Chemical
Manufacturers
Association
(
CMA)
antimicrobial
exposure
study
and
the
Pesticide
Handlers
Exposure
Database
(
PHED).

For
the
occupational
handler
dermal
and
inhalation
risk
assessment,
the
short­
and
intermediate­
term
risks
calculated
at
baseline
exposure
(
no
gloves
and
no
respirators)
were
above
target
MOEs
for
all
scenarios
(
i.
e.,
dermal
MOEs
were
>
100
and
inhalation
MOEs
were
>
300).
Note,
however,
that
the
high
pressure
spray
application
method
in
the
agricultural
use
site
category
was
assessed
using
gloved
data.

Table
9
Short­,
Intermediate­
Term
Risks
for
Occupational
Handlers
MOE
c
Exposure
Scenario
Method
of
Application
Application
Rate
(
lb
ai/
gallon)
Quantity
Handled/
Treated
per
day
(
gallons)
Baseline
Dermal
(
a)
(
Target
MOE>
100)
PPE
Gloves
Dermal
(
b)
(
Target
MOE>
100)
Baseline
Inhalation
(
Target
MOE>
100)
Agricultural
Premises
and
Equipment
Low
Pressure
Handwand
10
270
No
Data
150,000
High
Pressure
Handwand
40
No
Data
5,100
210,000
Mopping
2
3,600
No
Data
220,000
Wiping
0.26
690
No
Data
59,000
Application
to
hard
surfaces
Trigger
Pump
Spray
0.0034
0.26
10,000
24,000
3,000,000
Fogger
Liquid
Pour
of
soluble
concentrate
0.163
lb
ai/
gal/
6,000
ft2
15,000
ft2
120
No
Data
4,500
Food
Handling
Low
Pressure
Handwand
2
1,800
No
Data
1,000,000
Mopping
2
4,900
No
Data
290,000
Wiping
0.26
940
No
Data
80,000
Application
to
indoor
hard
surfaces
Trigger
Pump
Spray
0.0025
0.26
7,300
17,000
2,100,000
Commercial/
Institutional
Premises
Application
to
indoor
Low
Pressure
Handwand
0.005
2
920
No
Data
510,000
Page
30
of
40
Table
9
Short­,
Intermediate­
Term
Risks
for
Occupational
Handlers
MOE
c
Mopping
2
2,400
No
Data
150,000
Wiping
0.26
470
No
Data
40,000
hard
surfaces
Trigger
Pump
Spray
0.26
7,100
17,000
2,100,000
Air
Deodorization
Aerosol
Spray
0.074%
ai
by
weight
3
16
oz
cans
4,100
9,700
1.200,000
Medical
Premises
and
Equipment
Low
Pressure
Handwand
2
920
No
Data
510,000
Mopping
45
110
No
Data
6,500
Wiping
0.26
470
No
Data
40,000
Application
to
indoor
hard
surfaces
Trigger
Pump
Spray
0.005
0.26
7,100
17,000
2,100,000
Air
Deodorization
Aerosol
Spray
0.074%
ai
by
weight
3
16
oz
cans
4,100
9,700
1,200,000
(
a)
Baseline
Dermal:
Long­
sleeve
shirt,
long
pants,
no
gloves.
(
b)
PPE
Dermal
with
gloves:
baseline
dermal
plus
chemical­
resistant
gloves.
c
MOE
=
NOAEL
(
mg/
kg/
day)
/
Daily
Dose
[
Where
short­
and
intermediate­
term
NOAEL
=
25
mg/
kg/
day
for
dermal
exposure
and
short­,
and
intermediate­
term
inhalation
NOAEL
=
50
mg/
kg/
day
for
inhalation
exposure].
Target
MOE
is
100
for
dermal
exposure
and
300
for
inhalation
exposure.

Postapplication
Exposure
and
Risk.
For
most
of
the
occupational
scenarios,
postapplication
dermal
exposure
is
not
expected
to
occur
or
is
expected
to
be
negligible
based
on
the
application
rates
and
chemical
properties
of
the
chemical.
Postapplication/
bystander
inhalation
exposures,
however,
were
assessed
for
entry
into
a
building
after
a
fogging
application.
The
representative
building
selected
was
a
poultry
barn.
The
Agency
used
the
MCCEM
(
Multi­
Chamber
Concentration
and
Exposure
Model)
to
estimate
postapplication/
bystander
exposures.
The
calculated
inhalation
MOEs
were
above
the
target
MOE
of
300
for
all
fogging
postapplication
scenarios.

9.0
INCIDENTS
A
detailed
summary
of
the
human
incident
data
is
presented
in
the
memorandum
from
J.
Chen
D316276,
July
2005.
Below
is
a
brief
summary
of
this
information.
The
Agency
consulted
the
following
databases
for
poisoning
incident
data
for
4­
t­
amylphenol
and
its
salts,
and
other
similar
phenolic
disinfectant
compounds:

(
1)
OPP
Incident
Data
System
(
IDS)
­
The
Incident
Data
System
of
The
Office
of
Pesticide
Programs
(
OPP)
of
the
Environmental
Protection
Agency
(
EPA)
contains
reports
of
incidents
from
various
sources,
including
registrants,
other
federal
and
state
health
and
environmental
agencies
and
individual
consumers,
submitted
to
OPP
since
1992.
Reports
submitted
to
the
Incident
Data
System
represent
anecdotal
reports
or
Page
31
of
40
allegations
only,
unless
otherwise
stated.
Typically
no
conclusions
can
be
drawn
implicating
the
pesticide
as
a
cause
of
any
of
the
reported
health
effects.
Nevertheless,
sometimes
with
enough
cases
and/
or
enough
documentation
risk
mitigation
measures
may
be
suggested.
(
2)
Poison
Control
Centers
­
as
the
result
of
a
data
purchase
by
EPA,
OPP
received
Poison
Control
Center
data
covering
the
years
1993
through
1998
for
all
pesticides.
Most
of
the
national
Poison
Control
Centers
(
PCCs)
participate
in
a
national
data
collection
system,
the
Toxic
Exposure
Surveillance
System,
which
obtains
data
from
about
65­
70
centers
at
hospitals
and
universities.
PCCs
provide
telephone
consultation
for
individuals
and
health
care
providers
on
suspected
poisonings,
involving
drugs,
household
products,
pesticides,
etc.
(
3)
California
Department
of
Pesticide
Regulation
­
California
has
collected
uniform
data
on
suspected
pesticide
poisonings
since
1982.
Physicians
are
required,
by
statute,
to
report
to
their
local
health
officer
all
occurrences
of
illness
suspected
of
being
related
to
exposure
to
pesticides.
The
majority
of
the
incidents
involve
workers.
Information
on
exposure
(
worker
activity),
type
of
illness
(
systemic,
eye,
skin,
eye/
skin
and
respiratory),
likelihood
of
a
causal
relationship,
and
number
of
days
off
work
and
in
the
hospital
are
provided.
(
4)
National
Pesticide
Telecommunications
Network
(
NPTN)
­
NPTN
is
a
toll­
free
information
service
supported
by
OPP.
A
ranking
of
the
top
200
active
ingredients
for
which
telephone
calls
were
received
during
calendar
years
1984­
1991,
inclusive,
has
been
prepared.
The
total
number
of
calls
was
tabulated
for
the
categories
human
incidents,
animal
incidents,
calls
for
information,
and
others.

There
are
some
reported
incidents
associated
with
exposure
to
end­
use
products
containing
4­
tert­
amylphenol.
Dermal,
ocular
and
inhalation
are
the
primary
routes
of
exposure.
Dermal
exposure
is
considered
as
a
very
important
route
of
exposure.
Most
of
the
incidents
are
related
to
irritation
reaction.
The
most
common
symptoms
reported
for
cases
of
inhalation
exposure
were
respiratory
irritation/
burning,
irritation
to
mouth/
throat/
nose,
coughing/
choking,
shortness
of
breath,
dizziness,
flu­
like
symptoms,
and
headache.
Eye
pain,
burning
of
eyes,
conjunctivitis,
blurring
vision,
and
acute
inflammation
have
been
reported
in
ocular
exposure
incidents.
Neurological
effects,
such
as
dizziness,
headache
and
blurred
vision
have
also
been
reported.

10.0
ENVIRONMENTAL
RISK
A
detailed
ecological
hazard
and
environmental
risk
assessment
for
4­
t­
amylphenol
and
its
salts
is
presented
in
the
attached
memorandum
(
memo
from
D.
Bays,
October
2005).
A
brief
summary
is
presented
below.

Environmental
Modeling/
Exposure.
The
limited
environmental
exposure
resulting
from
indoor
uses
of
4­
t­
amylphenol
and
its
salts
is
not
anticipated
to
cause
adverse
effects
to
terrestrial
or
aquatic
organisms.

Ecological
Hazard
and
Risk.
The
registrant
has
not
submitted
any
ecological
effects
data
to
support
this
RED.
The
only
data
that
was
available
was
found
in
the
peer­
reviewed
literature.
None
of
these
studies
met
current
guideline
requirements
and
therefore,
could
not
be
used
in
a
risk
Page
32
of
40
assessment.
There
is
a
concern
about
the
possibility
of
endocrine
disruption
in
fish,
since
4­
t­
amylphenol
is
considered
an
ecoestrogen.
This
was
documented
in
several
studies
on
carp
(
Cyprinus
carpio),
whose
findings
were
included
in
the
ecotoxicity
chapter.
However,
since
this
chemical
is
restricted
to
indoor
uses
only,
the
possibility
for
exposure
of
fish
to
4­
t­
amylphenol
would
be
limited.
The
registrant
does
have
to
submit
three
ecological
effects
studies
on
the
acute
toxicity
of
this
chemical.
These
include
an
avian
acute
oral
toxicity
test,
preferably
using
the
bobwhite
quail,
(
850.2100/
71­
1),
a
freshwater
fish
acute
toxicity
test,
preferably
using
the
rainbow
trout,
(
850.1075/
72­
1),
and
an
acute
freshwater
invertebrate
test
(
850.1010/
72­
2).
These
tests
are
required
in
order
to
document
potential
acute
toxicity
to
these
organisms
in
the
unlikely
event
that
exposure
to
4­
t­
amylphenol
and
its
salts
does
occur.

The
acute
toxicity
data
for
4­
t­
amylphenol
are
summarized
on
Table
10.
As
shown
in
Table
10,
acute
toxicity
for
freshwater
fish
ranged
from
2.50
mg/
L
to
16
mg/
L
in
the
fathead
minnow.
The
first
study
was
conducted
using
criteria
similar
to
OPP/
OPPTS
guidelines
and
would
have
more
weight
than
the
second
study
which
did
not
provide
any
information
on
how
the
study
was
conducted.
Therefore,
the
data
indicates
that
4­
t­
amylphenol
is
moderately
toxic
to
coldwater
species,
such
as
the
fathead
minnow.
The
fathead
minnow
is
considered
to
be
less
sensitive
than
the
bluegill.
Also
shown
in
Table
10,
acute
toxicity
to
shrimp
was
LC50
=
1.7
mg/
L.
This
indicated
that
4­
t­
amylphenol
was
moderately
toxic
to
shrimp.
The
study
does
not
meet
current
guideline
requirements
and
could
not
be
used
in
a
risk
assessment.

Table
10.
Acute
Toxicity
of
4­
t­
amylphenol
and
salts
Organism
Results
­
LC50
(
mg/
L)
(
95%
Confidence
Limit)
Toxicity
Category
Comments
Reference
Freshwater
Fish
Fathead
minnow
(
Pimephales
promelas)
2.50
(
1.87
­
3.34)
moderately
toxic
­
96h
test
duration;
­
flow­
through
bioassay
­
caused
necrosis
in
fish
Holcombe,
G
W
et
al.
1984
Environ
Pollut
ser
A
Ecol
Biol
35:
367­
81
Fathead
minnow
(
Pimephales
promelas)
16
Slightly
toxic
­
No
information
available
on
the
test
parameters
Russon,
C
L
et
al.
1997
Environ.
Toxicol.
Chem
16:
948
Marine/
Estuarine
Invertebrates
Shrimp
(
Crangon
septemspinosa)
96h
LC50
=
1.7
mg/
L
Moderately
toxic
­
96h
test
duration;
­
aerated
gently
and
changed
at
49
hours
McLeese,
D
W
1981
Chemosphere
10(
7):
723
Endocrine
Disruption
Effects
in
Fish.
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
the
recommendations
of
its
Endocrine
Disruptor
Screening
and
Testing
Advisory
Committee
(
EDSTAC),
EPA
determined
that
there
was
scientific
basis
for
including,
as
Page
33
of
40
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
effects
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).
When
the
appropriate
screening
and/
or
testing
protocols
being
considered
under
the
Agency's
EDSP
have
been
developed,
4­
t­
amylphenol
and
its
salts
may
be
subjected
to
additional
screening
and/
or
testing
to
better
characterize
effects
related
to
endocrine
disruption.

4­
t­
Amylphenol
was
estrogenic
in
a
number
of
different
fish
models
from
the
in
vitro
rainbow
trout
ER
competitive
binding
assay
(
MED)
to
in
vivo
medaka
full
life
cycle
tests
(
Seki
et
al.,
2003)
as
summarized
in
the
table
below.
Many
types
of
estrogenic
or
endocrine
disruptive
responses
were
observed
such
as
increased
expression
of
vitellogening
(
Vtg)
mRNA
and
protein,
sex
reversal,
and
reduction
of
P450
11­
 
hydoxylase
levels.
The
estrogenic
LOEC
varied
among
models,
while
it
took
a
4­
t­
amylphenol
concentration
of
­
3.7/­
3.3
log
M
to
increase
Vtg
mRNA
expression
in
trout
liver
slices
in
vitro,
a
concentration
of
only
­
6.5
log
M
increased
Vtg
protein
levels
in
medaka
full
life
cycle
tests.
Efficacy
of
the
4­
t­
amylphenol
estrogenic
response
was
nearly
equal
to
the
maximum
response
elicited
by
exposure
to
17
 
­
estradiol
(
E2).
The
effect
of
4­
t­
amylphenol
exposure
on
cell
viability
was
measured
in
a
number
of
these
studies
and
was
found
to
occur
at
concentrations
above
the
estrogenic
LOEC,
although
the
toxic
concentration
of
4­
t­
amylphenol
was
never
more
than
an
order
of
magnitude
greater
than
the
estrogenic
LOEC.
While
there
are
only
a
small
number
of
studies
of
the
estrogenic
effects
4­
t­
amylphenol
the
relative
estrogenic
potency
of
4­
t­
amylphenol
appeared
to
be
an
order
of
magnitude
higher
in
fish
than
in
mammals.
This
chemical
is
also
on
a
European
list
of
"
Chemicals
purported
to
be
endocrine
Disrupters"
(
IEH,
2005;
page
85
in
the
Consumer
Products
table
which
references
Miller
et
al.,
2001
and
Schultz
et
al.,
2000,
and
a
priority
list
produced
by
an
European
consulting
firm).

Examples
of
4­
t­
amylphenol
affecting
the
reproductive
processes
of
carp
have
been
reported
in
the
peer­
reported
literature.
Since
the
use
pattern
for
this
chemical
is
restricted
to
indoor
uses,
exposure
to
fish,
such
as
carp,
should
be
limited.
Therefore,
no
additional
testing
for
endocrine
disruption
effects
on
fish
is
necessary
at
this
time.

Table
11:
Examples
of
4­
t­
amylphenol
Affecting
the
Endocrine
System
in
Fish
Organism
Results
Toxicity
Category
Comments
Reference
Male
common
carp
(
Cyprinus
carpio)
caused
formation
of
oviducts
in
male
fish
and
reduced
the
number
of
primordial
germ
cells
in
gonads
identified
as
an
ecoestrogen
­
test
concentration
0.14
mg/
L
­
exposed
embryos
and
fingerlings
at
various
ages
Gimeno
et
al.
1997
Environ
Sci
Technol
31(
10):
2884­
2890.

Male
common
carp
(
Cyprinus
carpio)
30­
day
EC50
for
oviduct
formation
=
63
ug/
L
NOEC
for
oviduct
identified
as
causing
endocrine
­
120
male
carp
tested
­
nominal
concentrations
of
100,
320,
&
1000
ug/
L
were
tested
Gimeno,
S.
et
al.
1998a
Aquatic
Toxicology
(
Amsterdam)
Page
34
of
40
Table
11:
Examples
of
4­
t­
amylphenol
Affecting
the
Endocrine
System
in
Fish
Organism
Results
Toxicity
Category
Comments
Reference
formation
=
<
36
ug/
L
primordial
germ
cells
lower
in
treated
fish
NOEC
for
vitellogenin
induction
=
90­
256
ug/
L
disruption
effects
­
160
day
test
duration
­
intermittent
flow
through
system
43:
77­
92.

Cultured
hepatocytes
from
genetically­
unifor
m,
all
male,
F1­
hybrid
progenies
of
common
carp
(
Cyprinus
capio)
vitellogenin
induction
in
carp
hepatocytes
with
LOEC
ranging
from
5­
50
uM,
cytotoxic
at
100uM
identified
as
causing
endocrine
disruption
effects
­
six
month
old
hepatocytes
with
fully
mature
testes
containing
mature
sperm
Smeets,
J.
M.
et
al.
1999.
Toxicol.
Sci.
50(
2):
206­
213.

Trout
RTH
149
Recombinant
trout­
ER
Estrogenic
LOEC=
­
6
log
M;
IC50=
7.6x10­
7
M
Identifid
as
causing
endocring
disruption
effects
­
relative
potency
is
0.036
approximately
75%
of
maximum
E2
Hornung
et
al.
2003
Partial
life
cycle
carp
(
Cyprinus
carpio)
Estrogenic
LOEC=
­
6.2
log
M
Identified
as
causing
endocrine
disruption
effects
­
oviduct
development
in
male
Gimeno
et
al.
1996
Partial
life
cycle
Medaka
(
Oryzias
latipes)
Estrogenic
LOEC=
5.8
log
M
Identified
as
causing
endocrine
disruption
effects
­
sex
reversal;
Inhibition
of
P450
11B
hydroxylase
mRNA
levels
Yokota
et
al.
2005
Full
life
cycle
Medaka
(
Oryzias
latipes)
Estrogenic
LOEC=
­
6.5;
cytotoxicity
=
­
5.2
F0
and
­
5.8
F1
Identified
as
causing
endocrine
disruption
effects
­
Vtg
induction
at
­
6.5
log
M
Seki
et
al.
2003
Rainbow
trout
cytosol
ER
competitive
binding
Estrogenic
LOEC=
­
5
log
M;
IC50=
2.2x10­
4
M;
RBA
0.004%
Identified
as
causing
endocrine
disruption
effects
Tapper
et
al.
2005
Male
rainbow
trout
liver
slice/
Vtg
gene
expression
Estrogenic
LOEC=
­
3.7
log
M;
IC50=
1.8x10­
4
M;
cytotoxicity=
­
3
log
M
Identified
as
causing
endocrine
disruption
effects
­
relative
potency
=
0.004%
approximately
75%
of
maximum
E2
Tapper
et
al.
2005
Male
common
carp
(
Cyprinus
carpio)
elevated
levels
of
vitellogenin,
inhibition
of
spermatogenesis,
disappearance
of
spermatozoa
and
identified
as
causing
endocrine
disruption
effects
and
no
mortality
or
­
3
month
test
duration
­
nominal
concentrations
of
32,
100,
320
and
1000
ug/
L
were
tested
Gimeno
et
al.
1998b
Aquatic
Toxicology
(
Amsterdam)
43:
93­
109.
Page
35
of
40
Table
11:
Examples
of
4­
t­
amylphenol
Affecting
the
Endocrine
System
in
Fish
Organism
Results
Toxicity
Category
Comments
Reference
spermatogenic
cysts,
reduced
diameter
of
seminiferous
lobules,
reduced
spermatocrit
values
and
early
appearance
of
ovo­
testes
LOAEL=
0.032
mg/
L
growth
effects
E2=
17
 
­
estradiol;
;
Vtg
=
vitellogening;
RBA
=
relative
binding
affinity
Vitellogenin,
an
egg
yolk
pre­
cursor
protein
is
produced
in
female
trout
liver
and
transported
to
the
gonad
for
the
production
of
eggs.
Male
trout
retain
ER
in
the
liver
and
the
ability
to
produce
vitellogenin,
and
can
be
induced
to
do
so
upon
exposure
to
estrogen
(
17
 
­
estradiol;
E2),
or
estrogenic
chemicals.

Environmental
Risk
Assessment
The
indoor
uses
of
4­
tert­
amylphenol
and
its
salts
considered
in
this
RED
make
it
unlikely
that
any
appreciable
exposure
to
terrestrial
or
aquatic
organisms
would
occur
when
4­
t­
amylphenol
and
its
salts
are
used
according
to
label
directions.
Even
though
there
is
a
low
potential
for
risk
due
to
the
lack
of
expected
environmental
exposure
from
the
registered
uses
of
this
product,
three
acute
toxicity
studies
(
avian
acute
oral
toxicity
test
[
850.2100/
71­
1]
preferably
using
the
bobwhite
quail;
freshwater
fish
acute
toxicity
test
[
850.1075/
72­
1]
preferably
using
the
rainbow
trout;
and
an
acute
freshwater
invertebrate
test
[
850.1010/
72­
2]),
will
need
to
be
submitted
by
the
registrant
in
order
to
determine
potential
toxicity
to
birds
and
aquatic
organisms
in
the
unlikely
event
that
exposure
does
occur.

Endangered
Species
Considerations
The
Agency
has
developed
the
Endangered
Species
Protection
Program
to
identify
pesticides
whose
use
may
cause
adverse
impacts
on
endangered
and
threatened
species,
and
to
implement
mitigation
measures
that
address
these
impacts.
The
Endangered
Species
Act
requires
federal
agencies
to
ensure
that
their
actions
are
not
likely
to
jeopardize
listed
species
or
adversely
modify
designated
critical
habitat.
To
analyze
the
potential
of
registered
pesticide
uses
to
affect
any
particular
species,
EPA
puts
basic
toxicity
and
exposure
data
developed
for
risk
assessments
into
context
for
individual
listed
species
and
their
locations
by
evaluating
important
ecological
parameters,
pesticide
use
information,
the
geographic
relationship
between
specific
pesticide
uses
and
species
locations,
and
biological
requirements
and
behavioral
aspects
of
the
particular
species.
A
determination
that
there
is
a
likelihood
of
potential
impact
to
a
listed
species
may
result
in
limitations
on
use
of
the
pesticide,
other
measures
to
mitigate
any
potential
impact,
or
consultations
with
the
Fish
and
Wildlife
Service
and/
or
the
National
Marine
Fisheries
Service
as
necessary.

Based
on
the
low
likelihood
of
environmental
exposure
from
the
registered
indoor
uses
of
4­
t­
amylphenol
and
its
salts
to
fish,
aquatic
invertebrates,
and
aquatic
plants,
adverse
impacts
to
endangered
species
are
not
expected
from
the
registered
uses
of
4­
t­
amylphenol
and
its
salts.
Page
36
of
40
11.0
DEFICIENCIES/
DATA
NEEDS
Hazard
Data
Gaps.
There
are
several
data
gaps
for
4­
t­
amylphenol.
The
existing
acute
toxicity
data
iincomplete
and
4
new
acute
toxicity
studies
using
the
technical
grade
active
ingredient
must
be
conducted.
The
current
hazard
database
is
inadequate
to
support
the
indirect
food
use
of
4­
t­
amylphenol.
The
ADTC
(
2005)
identified
the
following
data
gaps
for
4­
t­
amylphenol:

Acute
toxicity
testing:
870.1200
(
acute
dermal),
870.1300
(
acute
inhalation),
870.2400
(
primary
eye
irritation,
and
870.2600
(
dermal
sensitization)
90
oral
subchronic
study
in
the
rat,
modified
to
examine
endocrine
disrupter
effects
Developmental
toxicity
study
in
the
rabbit
2­
generation
reproduction
study
in
the
rat
or
other
available
information
on
reproductive
toxicity
Repeat
dose
inhalation
toxicity
study
of
at
least
28
days
duration
Because
4­
t­
amylphenol
appears
to
cause
severe
dermal
irritation
and
is
a
sensitizer
following
repeated
dermal
exposure,
a
dermal
toxicity
study
with
the
diluted
end­
use
formulated
product
would
be
helpful
to
ensure
that
clothing
and
diapers
containing
4­
t­
amylphenol
will
not
be
irritating
to
skin.

Dietary
Data
Gaps.
In
the
absence
of
chemical­
specific
data,
the
Agency
used
a
10%
migration
factor
for
the
dietary
assessment.
The
Agency
requests
confirmatory
data
to
support
the
10%
migration
factor.

Confirmatory
data
are
needed
to
show
whether
residues
would
be
absorbed
into
treated
surfaces,
especially
wood
surfaces,
of
feeding
devices
and
not
be
removed
by
scrubbing
with
soap
and
rinsing
with
water.
If
the
antimicrobial
residues
are
absorbed
into
the
wood,
these
residues
would
be
available
for
livestock
ingestion.
This
finding
could
entail
the
need
to
generate
data
for
large
animals
including
livestock
and
poultry
metabolism
studies,
analytical
methods
for
livestock
and
poultry
tissues
and
residue
data
for
livestock
and
poultry.

Ecological
Data
Gaps.
For
indoor
uses,
an
acute
oral
toxicity
study
using
the
technical
grade
of
the
active
ingredient
(
TGAI)
is
required
to
establish
the
toxicity
of
4­
tert­
amylphenol
and
its
salts
to
birds.
The
preferred
test
species
is
either
mallard
duck
(
a
waterfowl)
or
northern
bobwhite
quail
(
an
upland
game
bird).
Two
avian
acute
toxicity
studies
were
found
in
the
Agency's
files
for
4­
tert­
amylphenol
or
its
salts.
The
tests
were
conducted
in
1974
using
the
bobwhite
quail
(
MRID
#
240116618)
and
mallard
duck
(
MRID
#
011504216).
The
tests
were
conducted
using
antiquated
procedures
and
do
not
meet
the
current
guideline
requirements.
The
results
showed
moderate
toxicity,
which
makes
it
important
that
a
test
using
current
guideline
requirement
be
conducted
by
the
registrant.
Avian
acute
oral
toxicity
testing
(
850.2100/
71­
1),
preferably
using
the
bobwhite
quail,
is
required
to
support
the
currently
registered
uses
of
4­
tert­
amylphenol
and
it
salts.

Freshwater
fish
toxicity
studies
using
the
TGAI
are
required
to
establish
the
toxicity
of
4­
tert­
amylphenol
to
fish.
Data
are
generally
required
for
only
one
species.
Testing
in
two
fish
Page
37
of
40
species
is
required
for
stable
chemicals
with
high
volume
effluents
(
e.
g.,
including,
but
not
limited
to,
egg
washing,
fruit
and
vegetable
rinses,
swimming
pools
or
materials
preservatives)
and
if
the
LC50
in
the
first
species
is
greater
than
(>)
1
ppm.
The
preferred
test
species
are
rainbow
trout
(
a
coldwater
fish)
and
bluegill
sunfish
(
a
warmwater
fish),
although
other
test
species
identified
in
the
OPPTS
Guideline
(
i.
e.,
OPPTS
850.1075
(
e)(
4)(
i)(
A))
may
also
be
used.
No
freshwater
fish
acute
toxicity
studies
were
identified
from
peer­
reviewed
literature.
Two
fish
studies
were
found
in
the
agency's
files,
but
no
studies
have
been
submitted
to
support
registration
of
4­
tert­
amylphenol.
The
first
study
(
MRID
#
240116619)
was
conducted
in
1974
and
tested
both
rainbow
trout
and
bluegill
sunfish
in
the
same
study.
The
second
study(
MRID
#
444742­
08)
was
conducted
in
1992
using
zebra
fish,
but
only
tested
one
concentration
of
TGAI.
Neither
of
these
studies
meets
current
guideline
requirements
and
cannot
be
used
in
a
risk
assessment.
Freshwater
fish
acute
toxicity
testing
(
850.1075/
72­
1)
on
one
species
preferably
the
rainbow
trout
is
required
to
support
the
currently
registered
uses
of
4­
tert­
amylphenol
and
its
salts.

A
freshwater
aquatic
invertebrate
toxicity
test
using
the
TGAI
is
required
to
establish
the
toxicity
of
a
pesticide
to
aquatic
invertebrates.
The
preferred
test
species
is
Daphnia
magna
or
Daphnia
pulex.
No
toxicity
studies
were
identified
for
these
species
in
peer­
reviewed
literature.
No
studies
have
been
submitted
by
registrants
to
support
the
registered
uses
of
4­
tert­
amylphenol
and
its
salts.
Freshwater
invertebrate
acute
toxicity
testing
(
850.1010/
72­
2)
is
required
for
the
currently
registered
uses
of
4­
tert­
amylphenol
and
its
salts.

Residential/
Occupational
Data
Gaps.
Confirmatory
worker
exposure
data
are
necessary,
due
to
the
significant
limitations
of
the
existing
exposure
data
used
in
this
assessment.
The
Agency
is
requesting
worker
exposure
studies
that
evaluate
both
dermal
(
Guideline
875.1200)
and
inhalation
(
Guideline
875.1400)
exposure
for
indoor
uses.
The
Agency
also
requires
confirmation
of
descriptions
of
human
activity
(
875.2800)
associated
with
the
uses
assessed
in
this
document.
In
addition,
the
Agency
requests
confirmatory
data
to
support
the
assumption
that
only
5%
of
4­
t­
amylphenol
is
transferred
from
treated­
textiles/
diapers
to
skin.

Environmental
Fate
Data
Gaps:
4­
t­
Amylphenol
and
its
potassium
and
sodium
salts
are
registered
as
indoor
use
products
and
minimum
environmental
fate
data
required
by
EPA
for
an
indoor
use
product
is
hydrolysis
(
161­
1).
However,
no
hydrolysis
data
as
indicated
in
the
U.
S.
Environmental
Protection
Agency's
Environmental
Fate
Data
Requirements
published
in
Pesticide
Assessment
Guidelines,
Subdivision
N,
§
161­
1
have
been
submitted
to
the
Agency
for
these
chemicals.

12.0
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