UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
MEMORANDUM
Date:
October
5,
2005
Subject:
Ecological
Hazard
and
Environmental
Risk
Assessment
for
4­
tertamylphenol
and
salts
to
be
included
in
the
RED.
(
DP
Barcode
316278;
Decision#
356355;
PC
Code
064101)

From:
David
C.
Bays,
Risk
Assessment
and
Science
Support
Branch
(
RASSB),
Antimicrobials
Division
(
7510W)

To:
Adam
Heyward,
Product
Manager,
#
34,
Antimicrobials
Division
(
7510W)
and
Killian
Swift,
Risk
Manager
Reviewer,
#
36,
Antimicrobials
Division
Thru:
Rick
Petrie,
Team
Leader,
RASSB3,
AD
and
Norm
Cook,
Branch
Chief,
RASSB,
AD
RASSB
has
completed
the
Ecological
Hazard
and
Environmental
Risk
Assessment
for
4­
tertamylphenol
and
its
salts
(
Ecotoxicity
RED
chapter).
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
assessment.
There
is
a
concern
about
the
possibility
of
endocrine
disruption
in
fish,
since
4­
tert­
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
tert­
amylphenol
would
be
limited.
Therefore,
no
additional
testing
on
2
ecoestrogen
activity
is
required
for
this
RED.
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
tert­
amylphenol
and
its
salts
does
occur.

Summary
of
Uses:

4­
tertiary­
amylphenol,
and
salts
(
potassium
and
sodium)
are
a
disinfectant,
sanitizer,
and
deodorizer,
primarily
used
on
hard,
non­
porous
surfaces.
There
are
several
different
use
sites.
These
sites
include
disinfecting
equipment:
such
as
egg
hatching,
processing
and
milking
equipment;
eating
establishment
equipment
and
utensils;
food
marketing,
storage,
and
distribution
equipment
and
utensils;
hospital
critical
items,
such
as
those
that
enter
blood
or
living
tissue;
hospital
semi­
critical
items,
such
as
those
that
contact
mucosal
membranes;
hospital
non­
critical
items,
such
as
those
that
contact
only
unbroken
skin;
hospital
janitorial
equipment;
barber
and
beauty
shop
instruments
and
equipment;
morgues,
mortuaries
and
funeral
equipment;
human
bedding;
human
clothing;
laundry
equipment;
diapers;
refuse
and
solid
waste
containers;
tires;
farm
or
agricultural
equipment;
mushroom
house
equipment;
food
dispensing
equipment;
shoes;
closets;
bird
cages;
telephones;
door
knobs;
wheel
chairs;
light
switches;
metal
beds
and
springs;
office
machinery;
carpet
and
rugs.

A
second
major
use
site
is
the
treating
of
structures,
such
as
barns;
household
dwellings;
household
sickrooms;
buses;
ships;
railway
cars;
aircraft;
automobiles;
recreational
vehicles;
taxis;
limousines;
food
processing
plants;
canneries;
milk
processing
plants;
feed
mills
and
stores;
meat
processing
plants;
poultry
processing
plants;
frozen
food
plants;
beverage
processing
plants;
eating
establishments;
food
marketing,
storage
and
distribution
facilities;
food
stores
and
markets;
hospitals
which
includes
operating
rooms,
clinics,
wards,
labs,
and
waiting
rooms;
veterinary
hospitals;
morgues;
mortuaries;
bathrooms
which
include
toilet
bowls,
urinals,
toilet
tanks,
and
water
closets;
refuse
and
solid
waste
sites;
farm
or
agricultural
structures;
hotels;
day
care
facilities;
prisoner
holding
areas;
blood
banks;
kitchens;
supermarkets;
mushroom
house
environs;
schools;
business,
medical
and
dental
offices;
swine
facilities;
zoos;
kennels;
animal
research
facilities;
livestock
operations;
nursing
homes;
air
treatment
of
rooms
(
fogging).

A
potential
outdoor
use,
wood
protection
to
treat
unseasoned
forest
products,
is
apparently
no
longer
supported
by
any
registrant.
The
following
assessment
of
ecological
and
environmental
risk
is
therefore
based
only
on
indoor
uses
for
these
chemicals.

1.
Ecological
Toxicity
Data
3
a.
Toxicity
to
Terrestrial
Animals
(
1).
Birds,
Acute
and
Subacute
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
tertamylphenol
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.
Avian
dietary
toxicity
studies
using
the
TGAI
of
4­
t­
amylphenol
and
its
salts
are
not
required
for
the
indoor
uses
of
4­
t­
amylphenol
and
its
salts.

(
2)
Mammals
A
summary
of
the
mammalian
toxicity
of
4­
t­
amylphenol
and
its
salts
is
presented
in
the
"
Evaluation
of
Toxicology
Database
for
Reregistration
Eligibility
Decision
Document
Disciplinary
Chapter"
July
12,
2005,
memo
from
M.
Ottley
to
K.
Swift.

b.
Toxicity
to
Aquatic
Animals
(
1).
Freshwater
Fish,
Acute
Freshwater
fish
toxicity
studies
using
the
TGAI
are
required
to
establish
the
toxicity
of
4­
tertamylphenol
to
fish.
Data
are
generally
required
for
only
one
species.
Testing
in
two
fish
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
LC
50
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
tertamylphenol
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
4
conducted
in
1992
using
zebra
fish,
but
only
tested
one
concentration
of
TGAI.
Neither
of
these
studies
meet
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.

The
results
from
freshwater
fish
acute
toxicity
studies
obtained
from
peer­
reviewed
literature
are
summarized
in
the
table
below
(
Table
1).

Table
1.
Acute
Toxicity
of
4­
tert­
amylphenol
and
salts
to
Freshwater
Fish
Organism
Results
­
LC50
(
mg/
L)
(
95%
Confidence
Limit)
Toxicity
Category
Comments
Reference
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
As
shown
in
Table
1,
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/
OPTS
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
tertamylphenol
is
moderately
toxic
to
coldwater
species,
such
as
the
fathead
minnow.
The
fathead
minnow
is
considered
to
be
less
sensitive
than
the
bluegill.

(
2).
Freshwater
Fish,
Chronic
Fish
early
life
stage
testing
is
not
required
for
the
currently
registered
indoor
uses
of
4­
tamylphenol
and
its
salts.

(
3).
Freshwater
Invertebrates,
Acute
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.
5
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.

(
4).
Toxicity
to
Estuarine
and
Marine
Organisms
Acute
toxicity
testing
with
estuarine
and
marine
organisms
using
the
TGAI
is
not
required
for
the
indoor
uses
of
4­
t­
amylphenol
and
its
salts.
No
studies
on
marine/
estuarine
invertebrates
were
found
in
the
ECOTOX
database
(
EPA,
2002).
One
study
was
found
in
the
peer­
reviewed
literature.

Table
3:
Toxicity
of
4­
tert­
amylphenol
to
Marine/
Estuarine
Invertebrates
Organism
Results
Comments
Reference
Shrimp
(
Crangon
septemspinosa)
96h
LC50
=
1.7
mg/
L
­
96h
test
duration;
­
aerated
gently
and
changed
at
49
hours
McLeese,
D
W
1981
Chemosphere
10(
7):
723
As
shown
in
Table
3,
acute
toxicity
to
shrimp
was
LC50
=
1.7
mg/
L.
This
indicated
that
4­
tertamylphenol
was
moderately
toxic
to
shrimp.
The
study
does
not
meet
current
guideline
requirements
and
could
not
be
used
in
a
risk
assessment.

(
5).
Endocrine
Disruption
Effects
in
Fish
Examples
of
4­
tert­
amylphenol
and
other
phenol
chemicals
affecting
the
reproductive
processes
of
fish
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.
6
Table
4:
Examples
of
4­
tert­
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
formation
=
<
36
ug/
L
primordial
germ
cells
lower
in
treated
fish
NOEC
for
vitellogenin
induction
=
90­
256
ug/
L
identified
as
causing
endocrine
disruption
effects
­
120
male
carp
tested
­
nominal
concentrations
of
100,
320,
&
1000
ug/
L
were
tested
­
160
day
test
duration
­
intermittent
flow
through
system
Gimeno,
S.
et
al.
1998a
Aquatic
Toxicology
(
Amsterdam)
43:
77­
92.

Cultured
hepatocytes
from
geneticallyuniform
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
identified
as
causing
endocrine
disruption
effects
­
relative
potency
is
0.036
approx.
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
Estrogenic
LOEC
=
identified
as
­
Vtg
induction
at
­
6.5
Seki
et
al.
2003
7
Medaka
(
Oryzias
latipes)
­
6.5;
cytoxicity
=
­
5.2
F0
and
­
5.8
F1
causing
endocrine
disruption
effects
log
M
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
=
­
3.7log
M;
IC50
=
1.8x10­
4
M;
cytoxicity
=
­
3
log
M
identified
as
causing
endocrine
disruption
effects
­
relative
potency
=
0.004
%,
approx.
75%
of
maximum
E2
Tapper
et
al.
2005
Male
common
carp
(
Cyprinus
carpio)
elevated
levels
of
vitellogenin,
inhibition
of
spermatogenesis,
disappearance
of
speratozoa
and
spermatogenic
cysts,
reduced
diameter
of
seminiferous
lobules,
reduced
spermatocrit
values
and
early
appearance
of
ovotestes
LOAEL=
0.032
mg/
L
identified
as
causing
endocrine
disruption
effects
and
no
mortality
or
growth
effects
­
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.

C.
Toxicity
to
Plants
Terrestrial
and
aquatic
plant
testing
is
not
required
for
the
registered
indoor
uses
of
4­
tertamylphenol
and
its
salts.
There
were
no
aquatic
phytotoxicity
endpoints
reported
in
the
ECOTOX
database
(
EPA,
2002).
No
studies
were
found
in
the
peer­
reviewed
literature
that
addressed
plant
toxicity
to
this
chemical.

2.
Environmental
Risk
Characterization
A.
Environmental
Fate
Assessment
(
Refer
to
the
Environmental
Fate
Science
Chapter
of
8
this
RED)

B.
Environmental
Exposure
Assessment
Environmental
exposure
modeling
was
not
conducted
for
the
indoor
uses
of
4­
tert­
amylphenol
and
its
salts
considered
in
this
RED.

C.
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
tert­
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.

D.
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
tertamylphenol
and
its
salts
to
fish,
aquatic
invertebrates,
and
aquatic
plants,
adverse
impacts
to
endangered
species
are
not
expected
from
the
registered
uses
of
4­
tert­
amylphenol
and
its
salts..

REFERENCES
9
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S.,
Gerritsen,
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Bowmer,
T.,
and
Komen,
H.
(
1996)
Feminization
of
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Nature
384:
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Gimeno,
S.,
Komen,
H.,
Venderbosch,
P.
W.,
and
Bowner,
T.
(
1997)
Disruption
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Gimeno,
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[
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(
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Smeets,
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10
[
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ORD/
NHEERL/
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MED)­
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MN]

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