DATE:
July
7,
2004
MEMORANDUMSUBJECT
Phenol­
Report
of
the
Antimicrobials
Division
Toxicology
Endpoint
Selection
Committee.

FROM:
Timothy
F.
McMahon,
Ph.
D.
Chair,
ADTC
Antimicrobials
Division
(
7510C)

THROUGH:
John
Redden,
Roger
Gardner,
Stephen
Dapson,
Ph.
D.,
Karen
Hamernik,
Ph.
D.,
Melba
Morrow,
D.
V.
M.,
Sanyvette
Williams­
Foy,
D.
V.
M,
Jonathan
Chen,
Ph.
D.,
Timothy
Leighton,
Michelle
Centra,
Najm
Shamim,
Ph.
D.

PC
Codes:
068603
On
March
9,
2004,
the
Antimicrobials
Division
Toxicology
Endpoint
Selection
Committee
(
ADTC)
reviewed
the
available
Toxicology
data
for
Phenol
and
discussed
endpoint
selection
for
use
as
appropriate
in
occupational/
residential
exposure
risk
assessments.
The
potential
for
increased
susceptibility
of
infants
and
children
from
exposure
to
phenol
was
also
evaluated
by
the
committee
in
order
to
meet
the
statutory
requirements
of
the
Food
Quality
Protection
Act
(
FQPA)
of
1996.
The
conclusions
drawn
at
this
meeting
are
presented
in
this
report.
2
Committee
Members
in
Attendance
Members
present
were:
Timothy
F.
McMahon,
Ph.
D.
Stephen
Dapson,
Ph.
D.;
Jonathan
Chen,
Ph.
D.;
Timothy
Leighton;
John
Redden;
Karen
Hamernik,
Ph.
D.,
Michelle
Centra,
Roger
Gardner,
Ph.
D.,
.
Sanyvette
Williams,
D.
V.
M.;
Melba
Morrow,
D.
V.
M.,
Najm
Shamim,
Ph.
D.

Others
present:
Samantha
Jones
(
Versar),
Matthew
Martin
(
Versar),
Eric
Brown
(
Versar),
Kathryn
Boyle
(
RD).

Data
Evaluation
/
Report
Presentation
Timothy
F.
McMahon,
Ph.
D.

Senior
Toxicologist
3
COMMITTEE
MEMBERS
IN
ATTENDANCE
(
Signature
indicates
concurrence
unless
otherwise
stated)

Stephen
Dapson
Jonathan
Chen
Roger
Gardner
Karen
Hamernik
Tim
McMahon
(
chair)

Melba
Morrow
John
Redden
Sanyvette
Williams­
Foy
Najm
Shamim
Michelle
Centra
Tim
Leighton
4
INTRODUCTION
Phenol
is
an
antimicrobial
pesticide
active
ingredient
used
as
a
sanitizer,
bacteriostat,
fungicide/
fungistat,
tuberculocide,
disinfectant,
and
virucide
for
a
number
of
use
sites,
including
indoor
food
uses
(
eating
establishments
equipment
and
utensils),
indoor
residential
sites
(
bathroom
premises,
hard
surfaces,
diaper
pails,
indoor
premises,
dogs,
air
ducts),
indoor
non­
food
(
institutional/
industrial
floors,
industrial
premises/
equipment,
laundry
equipment,
paints)
indoor
medical
(
hospitals),
and
aquatic
non­
food
residential
(
swimming
pool
surfaces)

FORMULA:
C6H6O
Physical
Properties:

Active
ingredient:
Phenol
Color:
colorless
to
light
link
Physical
state:
crystalline
solid
Specific
gravity:
1.07
at
20
oC
pH:
mildly
acidic
Vapor
Pressure:
0.341
mmHg
at
25
oC;
2.48
mmHg
at
50
oC
41.3
mmHG
at
100
oC
Solubility:
67
g/
L
at
16
oC
Molecular
mass:
94.11
Melting
point:
43.0
oC
Boiling
point:
181.8
oC
at
760
mmHG
FQPA
HAZARD
CONSIDERATIONS
1.
Adequacy
of
the
Toxicity
Data
Base
The
ADTC
concluded
that
the
available
toxicity
database
for
phenol
was
adequate
for
hazard
characterization
for
the
registered
uses.
In
addition
to
several
reports
from
the
scientific
literature,
there
is
a
recent
(
2002)
updated
Toxicological
Profile
in
the
IRIS
database
for
phenol.
5
2.
Evidence
of
Neurotoxicity
The
ADTC
committee
noted
neurotoxic
signs
from
acute
dermal
toxicity
studies
(
Brown
et
al.
­
convulsions;
OTS
0515567/
86­
870001405­
tremors;
Conning
DM­
stimulation
of
motor
nerve
endings
or
spinal
motor
centers)
and
from
a
15
day
inhalation
study
­
tilting
plane
results
showed
an
effect
in
treated
rats).
There
were
no
neurotoxic
signs
noted
from
the
oral
studies
using
gavage
or
drinking
water
as
the
method
of
phenol
administration.
As
noted
in
the
IRIS
Toxicological
profile,
"
A
number
of
nervous
system
effects
have
been
observed
following
phenol
dosing.
Tremors
were
observed
in
one
animal
that
later
died
(
apparently
of
dehydration)
following
dosing
via
the
drinking
water
(
ClinTrials
BioResearch,
1998).
Tremors
have
also
been
observed
in
several
gavage
studies
in
rats
and
mice
(
NTP,
1983a;
Dow
Chemical
Co.,
1994;
Moser
et
al.,
1995).
However,
in
a
specialized
13­
week
neurotoxicity
study
in
male
and
female
rats
that
included
an
FOB
and
a
detailed
neurohistopathology
evaluation
(
ClinTrials
BioResearch,
1998),
the
only
observed
nervous
system
effects
were
tremors
in
one
animal
and
decreased
motor
activity
in
females.
A
short­
term
gavage
screening
study
(
Moser
et
al.,
1995)
found
that
the
only
effect
in
an
FOB
was
a
marginal
decrease
in
motor
activity
and
increased
rearing
post­
exposure."
This
effect
could
be
attributed
to
the
dehydration
observed
in
the
study,
however,
it
was
also
concluded
that
phenol
contributed
to
the
decreased
motor
activity.

3.
Developmental
Toxicity
Study
Conclusions
The
toxicity
profile
for
phenol
presented
several
developmental
and
reproductive
toxicity
studies
found
in
the
open
literature.
These
studies
are
also
referred
to
in
the
IRIS
update
as
well.
In
addition,
the
National
Toxicology
Program
conducted
developmental
toxicity
studies
in
both
rats
and
mice.
The
ADTC
considered
the
NTP
studies
as
well
as
the
published
report
by
Ryan
et
al.
(
2001)
to
be
acceptable
for
regulatory
purposes.
Published
reports
by
Kavlock
(
1990)
and
Bishop
(
1997)
were
considered
unacceptable
for
purposes
of
determining
the
developmental
toxicity
of
phenol,
based
on
study
design.

In
the
NTP
rat
developmental
toxicity
study,
phenol,
in
distilled
water,
was
administered
to
groups
of
23
rats/
dose
by
gavage
at
dose
levels
of
0,
30,
60,
or
120
mg/
kg/
day
from
gestation
days
(
GD)
6
to
15.
No
significant
maternal
toxicity
was
observed
up
to
the
high
dose
of
120
mg/
kg/
day
tested
in
this
study.
In
offspring,
the
only
effect
noted
was
a
significant
decrease
in
mean
fetal
body
weight,
but
no
teratogenic
effects
were
observed.
Therefore,
the
maternal
toxicity
LOAEL
is
greater
than
120
mg/
kg/
day
in
this
study,
and
the
Developmental
toxicity
LOAEL
is
120
mg/
kg/
day.

In
the
NTP
mouse
developmental
toxicity
study,
phenol
was
administered
in
distilled
water
to
groups
of
31­
36
mice/
dose
by
gavage
at
dose
levels
of
0,
70,
140,
or
280
mg/
kg/
day
from
gestation
days
(
GD)
6
to
15.
Clinical
signs
of
toxicity
were
observed
in
maternal
animals
at
a
dose
of
280
mg/
kg/
day,
which
included
signs
of
neurotoxicity
(
tremors,
ataxia,
lethargy).
In
addition,
maternal
body
weight
was
decreased
during
the
treatment
period
(
31%
decrease)
and
entire
gestation
period
(
28%
decrease).
In
offspring
at
the
280
mg/
kg/
day
dose,
an
increase
in
cleft
palate
was
observed
in
8
of
214
fetuses
(
3
litters),
although
this
increase
was
not
statistically
significant.
The
fetuses
exhibited
reduced
mean
fetal
weights
(
male
and
female
combined)
and
the
researchers
concluded
that
the
high­
dose
(
280
mg/
kg/
day)
6
was
fetotoxic
due
to
significant
reductions
(
18%)
in
mean
fetal
weight
in
treated
animals
when
compared
to
control.
The
Maternal
and
Developmental
toxicity
NOAEL
was
140
mg/
kg/
day,
and
the
Maternal
and
Developmental
toxicity
LOAEL
was
280
mg/
kg/
day
in
this
study.

In
a
non
­
guideline
developmental
toxicity
study
(
Narotsky,
M.
G.
and
R.
J.
Kavlock,
Journal
of
Toxicology
and
Environmental
Health
45:
145­
171,
[
1995]),
phenol
was
studied
for
effects
on
postnatal
growth
and
viability
of
prenatally
exposed
rodents
as
a
means
to
assess
the
developmental
toxicity
of
phenol
(
99+%
purity).
Phenol
was
administered
to
groups
of
17
Fischer
344
rats/
dose
at
concentrations
of
40
or
53.3
mg/
kg/
day
once
daily
from
gestation
days
(
GD)
6­
19
for
a
total
exposure
period
of
14
days.
Dams
were
observed
throughout
pregnancy.
Following
delivery
litters
were
examined
postnatally
and
after
final
examination,
dams
were
sacrificed
and
uterine
implantation
sites
were
counted.
Pups,
14
live
litters/
dose,
were
maintained
for
21
days.

There
were
no
treatment­
related
effects
in
mortality
(
100
%
survival)
of
rats
receiving
phenol
for
14
days.
Clinical
signs
of
toxicity
following
administration
of
phenol
were
observed
and
included
altered
respiration
(
e.
g.,
rales
and
dyspnea)
at
both
dose
levels.
Maternal
weight
loss
was
similar
to
control
levels
after
two
treatments
but
significantly
reduced
weight
gains
were
observed
after
4
and
10
treatments
between
GD
6­
20.
Maternal
body
weight
gain
was
reduced
21
and
24%
from
controls
in
animals
treated
with
40.0
and
53.3
mg/
kg/
day
phenol,
respectively.
The
Maternal
Toxicity
NOAEL
is
less
than
40
mg/
kg/
day
(
lowest
dose
tested).
The
Maternal
Toxicity
LOAEL
is
40
mg/
kg/
day,
based
on
reduced
body
weight,
body
weight
gain,
and
respiratory
distress
(
rales
and
dyspnea).

One
low­
dose
and
two
high­
dose
animals
experienced
full
resorption
resulting
in
significantly
reduced
litter
sizes
and
a
marginally
significant
increase
in
prenatal
loss
in
the
high­
dose
group.
The
three
dams
with
resorbed
litters
had
severe
respiratory
signs
and
an
additional
high­
dose
female
also
had
severe
respiratory
signs
with
excessive
perinatal
mortality
in
its
litter.
The
high­
dose
dam
had
markedly
reduced
pup
weights
on
postnatal
day
(
PND)
1
resulting
in
a
marginally
significant
reduction
for
the
group.
Kinked
tails
were
observed
in
2
of
the
4
survivors
in
this
litter.
The
Reproductive
toxicity
NOAEL
is
less
than
40
mg/
kgday
(
lowest
dose
tested).
The
Reproductive
toxicity
LOAEL
is
40
mg/
kg/
day,
based
on
increased
incidence
of
resorptions
and
significantly
reduced
litter
size.

The
percentage
loss
of
prenatal
litters
was
4,
13,
and
22%
for
0,
40,
and
53.3
mg/
kg/
day,
respectively.
Developmental
effects
were
evident
only
in
litters
with
dams
exhibiting
severe
respiratory
signs,
other
females
with
similar
respiratory
effects
successfully
maintained
apparently
normal
litters.
The
developmental
effects
of
phenol
were
isolated
to
four
litters:
Three
(
one
from
low
dose
group)
were
fully
resorbed
and
the
fourth
exhibited
high
perinatal
mortality.
Postnatal
loss
was
minimal
with
a
small
increase,
less
than
5%,
at
the
high­
dose.
Changes
in
pup
weights
were
minimal
and
did
not
vary
significantly
from
control
levels.
Kinked
tails
were
also
noted
in
one
litter
at
53.3
mg/
kg/
day.
The
Developmental
Toxicity
NOAEL
is
less
than
40
mg/
kg/
day
(
lowest
dose
tested).
The
Developmental
Toxicity
LOAEL
is
40
mg/
kg/
day,
based
on
increased
incidence
of
perinatal
loss.
7
4.
Reproductive
Toxicity
Study
Conclusions
In
a
two­
generation
reproduction
toxicity
study
conducted
by
Ryan
et
al
(
2001),
phenol
was
administered
to
groups
of
30
Sprague­
Dawley
rats/
sex/
dose
in
drinking
water
at
concentrations
of
200,
1000,
or
5000
ppm
(
14,
70,
and
310
mg/
kg/
day
for
males
and
20,
93,
and
350
mg/
kg/
day
for
females,
respectively,
for
both
generations).
There
were
treatment­
related
decreases
in
body
weight
and
body
weight
gain
in
P1
generation
rats
treated
with
phenol
compared
to
controls.
These
reductions
were
concomitant
with
decreases
in
food
and
water
consumption
and
observed
in
the
high­
dose
rats.
There
were
also
treatment­
related
decreases
from
controls
in
F1
body
weight
in
the
5000
ppm
phenol­
treated
rats.
The
lower
maternal
body
weight
may
have
contributed
to
the
lower
birth
weight
of
F1
generation
as
a
result
of
the
decreased
food
and
water
consumption
during
lactation
and
decreased
palatability.

The
Maternal
Toxicity
NOAEL
is
1,000
ppm
in
the
P1
and
F1
generations.
The
Maternal
Toxicity
LOAEL
is
5,000
ppm
based
on
decreases
in
water
and
food
consumption,
body
weight
(
average
11%
decrease
during
premating
weeks
1
and
10,
gestation
and
lactation)
and
body
weight
gain
(
average
18%
decrease
during
premating
weeks
1
through
10)
in
the
P1
and
F1
generations.
These
effects
are
associated
with
flavor
aversion
to
phenol
in
the
drinking
water.

There
were
no
treatment­
related
effects
on
reproductive
performance
in
either
generation
(
P1
and
F1).
The
estrus
cycle,
epididymal
sperm
count,
motility,
sperm
morphology,
testicular
sperm
count,
and
production
rate
were
unaffected
by
phenol
treatment
in
the
P1
and
F1
generations.
However,
the
percent
of
offspring
alive
after
PND
0
were
significantly
decreased
in
the
5000
ppm
treated
groups
with
a
10%
decrease
on
PND
4
for
the
P1
generation
and
decreases
of
28
and
24%
on
PND
4
and
7­
21,
respectively,
for
the
F1
generation.

The
Reproductive
Toxicity
NOAEL
is
greater
than
or
equal
to
5,000
ppm
in
the
P1
and
F1
generations
(
highest
dose
tested).
The
Reproductive
Toxicity
LOAEL
is
greater
than
5,000
ppm
in
the
P1
and
F1
generations
(
not
established).

There
were
treatment­
related
effects
for
both
F1
and
F2
generations
with
increases
in
litter
mortality
(
more
so
in
the
F2
generation)
and
reduced
offspring
body
weights
in
the
high­
dose
group.
This
occurred
concurrently
with
maternal
toxicity
(
decreased
maternal
body
weight);
believed
to
be
secondary
to
the
animals'
aversion
to
the
flavor
of
the
phenol­
treated
water
and
resulted
in
decreased
maternal
as
well
as
offspring
body
weight.
There
were
delays
in
vaginal
patency
of
F1
females
(
38.3
days
for
treated
females
vs.
34.6
days
for
control
females)
and
preputial
separation
of
F1
males
(
47.8
days
for
treated
males
vs.
44
days
for
control
males)
observed
with
decreases
in
pre­
and
post­
weaning
body
weights
in
the
high­
dose
group.
Therefore,
the
onset
of
puberty
was
delayed
and
attributed
to
decreased
food
and
water
consumption
and
reduced
body
weight.

The
Offspring
Toxicity
NOAEL
is
1,000
ppm.
The
Offspring
Toxicity
LOAEL
is
5,000
ppm
based
on
decreases
in
body
weight
of
F1
and
F2
offspring
(
5­
7%
on
PND
0;
15­
30%
on
PND
4­
21),
decreases
in
litter
survival
of
P1
and
F1
offspring
(
P1
generation:
90%
in
treated
animals
vs.
99%
in
control
animals
on
PND
4;
96%
in
treated
animals
vs.
100%
in
control
animals
on
PND
7­
21.
F1
generation:
67%
in
treated
animals
vs.
93%
in
control
animals
on
PND
4;
74%
in
treated
animals
vs.
98%
in
control
animals
on
PND
7­
21)
and
delays
in
8
preputial
separation
in
F1
males
(
47.8
days
for
treated
males
vs.
44
days
for
control
males)
and
vaginal
patency
in
F1
females
(
38.3
days
for
treated
females
vs.
34.6
days
for
control
females).

5.
Information
from
Literature
Sources
Information
describing
hazards
of
phenol
were
obtained
mainly
from
published
scientific
literature
on
the
toxicity
of
this
compound,
including
technical
reports
from
the
National
Toxicology
Program
(
ntp­
server.
niehs.
nih.
gov)
and
the
USEPA's
IRIS
website
(
epa.
gov/
iris)
.
Product
chemistry
data
were
obtained
from
the
Handbook
of
Physics
and
Chemistry,
64th
edition
(
CRC
Press),
1983.

6.
Pre­
and/
or
Postnatal
Toxicity
A.
Determination
of
Susceptibility
The
ADTC
concluded
that
there
is
no
evidence
for
susceptibility
of
phenol
from
the
available
data
on
developmental
and
reproductive
toxicity.

B.
Degree
of
Concern
Analysis
and
Residual
Uncertainties
The
ADTC
concluded
that
there
are
low
concerns
and
no
residual
uncertainties
for
preand
or
post­
natal
toxicity
with
phenol
for
any
of
the
available
studies.
Conservative
NOAELs
were
established
for
all
developmental
and
offspring
effects.
The
developmental
and
reproductive
toxicity
studies
conducted
with
phenol
provide
adequate
information
on
the
dose­
response
relationships
for
developmental
and
reproductive
toxicity
and
are
considered
adequate
studies
for
regulatory
purposes.

C.
Proposed
Hazard­
based
Special
FQPA
Safety
Factor(
s):

The
hazard
based
default
special
FQPA
safety
factor
can
be
removed
(
1X)
when
assessing
dietary
risks
resulting
from
the
uses
of
phenol.

7.
Recommendation
for
a
Developmental
Neurotoxicity
Study
The
ADTC
did
not
recommend
for
a
developmental
neurotoxicity
study.
9
HAZARD
IDENTIFICATION
1.
Acute
Reference
Dose
The
ADTC
determined
that
there
was
no
appropriate
endpoint
for
assessment
of
acute
dietary
exposure.
This
conclusion
was
based
upon
examination
of
the
hazard
data
which
might
be
used
in
support
of
such
an
endpoint.
Body
weight
effects
observed
were
not
considered
to
be
the
result
of
a
single
exposure.
There
were
no
other
effects
from
the
data
that
were
reflective
of
an
adverse
effect
from
a
single
exposure.
This
risk
assessment
was
not
required
and
therefore,
an
Acute
RfD
value
was
not
selected.

2.
Chronic
Reference
Dose
A
chronic
Reference
Dose
has
been
published
in
IRIS.
This
Reference
Dose
value
is
based
upon
an
unpublished
developmental
toxicity
study
conducted
according
to
GLP
guidelines
(
Argus
Research
Laboratories,
1997).
In
this
study,
pregnant
Crl:
CDRBR
VAF/
Plus
Sprague­
Dawley
rats
(
25
per
group)
received
phenol
by
oral
gavage
on
GDs
6
through
15.
Dosing
was
three
times
daily
with
0,
20,
40,
or
120
mg
phenol/
kg/
dosage
using
a
dosing
volume
of
10
mL/
kg.
The
corresponding
daily
doses
were
0,
60,
120,
and
360
mg/
kg­
day.
The
authors
noted
that
the
test
material
was
90%
phenol
United
States
Pharmacopeia
(
USP);
the
authors
adjusted
the
dosage
calculations
for
test
material
purity.

One
high­
dose
dam
died
on
GD
11.
The
study
authors
attributed
this
death
to
phenol
treatment
because
it
occurred
only
at
the
high
dose,
although
there
were
no
adverse
clinical
observations
and
no
abnormal
necropsy
findings
in
this
animal.
Other
high­
dose
animals
exhibited
excess
salivation
and
tachypnea
(
rapid
breathing).
There
were
no
other
treatment­
related
clinical
observations
and
no
treatment­
related
necropsy
findings.
Dose­
dependent
decreases
in
body
weight
of
the
exposed
animals
as
compared
with
the
controls
were
observed.
Statistically
significant
decreases
in
both
maternal
body
weight
(
8%)
and
body
weight
gain
(
38%
for
GD
6
B
16)
were
observed
at
the
high
dose;
although
a
statistically
significant
decrease
in
body
weight
gain
(
11%)
was
observed
at
the
mid
dose,
the
decrease
at
the
mid
dose
(
relative
to
controls)
in
absolute
maternal
weight
at
the
end
of
dosing
(
3%)
was
not
statistically
significant.
Dosedependent
decreases
in
food
consumption
were
also
observed
during
the
dosing
period
.
Fetal
body
weights
in
the
high­
dose
group
were
significantly
lower
than
those
of
the
controls,
by
5
B
7%.
The
high­
dose
group
had
a
statistically
significant
decrease
in
ossification
sites
on
the
hindlimb
metatarsals,
but
it
is
unlikely
that
this
small
change
is
biologically
significant.
The
incidence
of
litters
with
incompletely
ossified
or
unossified
sternal
centra
was
0/
23,
0/
25,
3/
23,
and
3/
24;
this
increase
was
not
statistically
significant.
There
were
small,
dose­
related
increases
in
the
number
of
litters
with
fetuses
with
"
any
alteration"
and
with
"
any
variation"
at
120
mg/
kg/
day
and
higher.
However,
neither
of
these
changes
was
statistically
significant,
and
the
response
was
not
clearly
dose­
related.
In
addition,
an
increase
in
total
variations
is
of
questionable
significance
in
the
absence
of
any
increase
in
individual
variations.
There
were
no
other
10
treatmentrelated
effects
on
uterine
contents,
malformations,
or
variations.

The
maternal
toxicity
NOAEL
was
60
mg/
kg­
day
and
the
maternal
toxicity
LOAEL
was
120
mg/
kg/
day
based
on
small
decreases
in
maternal
body
weight
gain.
The
developmental
toxicity
NOAEL
was
120
mg/
kg­
day
and
the
developmental
toxicity
LOAEL
was
360
mg/
kg/
day
based
on
decreased
fetal
body
weight
and
delayed
ossification.

The
results
of
this
study
are
supported
by
the
1983
NTP
developmental
toxicity
study
in
rats,
in
which
the
maternal
NOAEL
and
LOAEL
were
determined
to
be
greater
than
or
equal
to
120
mg/
kg/
day
and
greater
than
120
mg/
kg/
day,
respectively,
and
the
developmental
NOAEL
and
LOAEL
were
determined
to
be
60
and
120
mg/
kg/
day,
respectively.

Dose
and
Endpoint
for
Establishing
cRfD:
The
Developmental
Toxicity
NOAEL
of
60
mg/
kg/
day
was
established
from
the
1983
NTP
developmental
toxicity
study
in
rats
and
is
based
on
a
significant
reductions
from
the
control
in
mean
fetal
body
weight/
litter
at
the
LOAEL
of
120
mg/
kg/
day.

Chronic
RfD
=
60
mg/
kg
=
0.6
mg/
kg
100
Comments:
The
developmental
NOAEL
of
60
mg/
kg/
day
is
considered
sufficiently
conservative
as
a
chronic
RfD
value,
and
is
also
protective
of
infants
and
children
being
a
developmental
endpoint.

3.
Dermal
Absorption
Dermal
absorption
data
were
available
from
the
IRIS
Toxicological
profile
for
phenol.
From
the
available
data,
dermal
absorption
percentages
of
20­
50%
have
been
observed
from
in
vivo
and
in
vitro
studies.
The
ADTC
selected
the
50%
dermal
absorption
value
for
phenol
for
use
in
risk
assessments
as
a
conservative
value.
This
value
also
takes
into
account
the
irritant
properties
of
phenol
which
may
increase
its
dermal
absorption.

4.
Incidental
Oral:
Short­
and
Intermediate­
term
Study
selected:
Developmental
toxicty
in
Rats
(
NTP,
1983)

In
a
prenatal
developmental
toxicity
study
(
Jones­
Price,
Ledoux,
Reel,
et
al.
1983)
phenol,
in
distilled
water,
was
administered
to
groups
of
23
female
CD
rats/
dose
by
gavage
at
dose
levels
of
0,
30,
60,
or
120
mg/
kg/
day
from
gestation
days
(
GD)
6
to
15.
Females
were
weighed
daily
during
treatment
11
and
observed
for
clinical
signs
of
toxicity.
A
total
of
20­
23
females/
group
were
confirmed
to
be
pregnant
at
sacrifice
on
GD
20.
The
gravid
uterus
of
each
dam
was
weighed
and
the
urine
contents
examined
for
implantation
sites
and
fetus
vitality
(
live,
dead,
or
reabsorbed).
Each
live
fetus
was
weighed
and
examined
for
external,
visceral,
and
skeletal
malformations.

There
were
no
treatment­
related
clinical
signs,
increases
in
mortality
(
100%
survival),
or
decreases
in
body
weight
and
body
weight
gain
in
rats
dosed
with
phenol.
The
Maternal
toxicity
NOAEL
is
greater
than
or
equal
to
120
mg/
kg/
day
(
highest
dose
tested).
The
Maternal
toxicity
LOAEL
is
greater
than
120
mg/
kg/
day
(
not
established).

There
were
no
changes
in
reproductive
parameters
in
treated
animals
when
compared
to
controls.
The
Reproductive
toxicity
NOAEL
is
greater
than
or
equal
to
120
mg/
kg/
day
(
highest
dose
tested).
The
Reproductive
toxicity
LOAEL
is
greater
than
120
mg/
kg/
day
(
not
established).

There
were
no
treatment­
related
effects
on
mean
live
fetal
body
weight/
litter
in
the
low­
and
mid­
dose
treated
groups.
However,
a
significant
reductions
from
the
control
in
mean
fetal
body
weight/
litter
was
observed
in
the
high­
dose
(
120
mg/
kg/
day)
group.
There
was
no
evidence
of
teratogenicity
observed
in
the
rats
following
administration
of
phenol.
The
Developmental
toxicity
NOAEL
is
60
mg/
kg/
day.
The
Developmental
toxicity
LOAEL
is
120
mg/
kg/
day,
based
on
reduced
fetal
weight.

Endpoint
for
risk
assessment:
The
Developmental
Toxicity
NOAEL
of
60
mg/
kg/
day
was
established
from
the
developmental
toxicity
study
in
rats
(
Jones­
Price,
Ledoux,
Reel,
et
al.
1983)
based
on
a
significant
reduction
from
the
control
in
mean
fetal
body
weight/
litter
at
the
LOAEL
of
120
mg/
kg/
day.

Comments:
The
endpoint
selected
is
appropriate
for
the
route
and
duration
of
this
risk
assessment.
In
addition,
the
developmental
toxicity
NOAEL
of
60
mg/
kg/
day
is
considered
conservative
and
protective
of
infants
and
children.
Effects
observed
in
the
Narotsky
and
Kavlock
study
(
1995,
described
above
in
the
developmental
toxicity
conclusions
section)
at
53
mg/
kg/
day
provide
support
for
the
selection
of
the
60
mg/
kg/
day
as
an
endpoint
value.

5.
Dermal
Exposure:
Short­
and
Intermediate­
term
Study
selected:
See
Incidental
Oral:
Short­
and
Intermediate­
Term
Endpoint
for
risk
assessment:
The
Developmental
Toxicity
NOAEL
of
60
mg/
kg/
day
was
established
from
the
developmental
toxicity
study
in
rats
(
Jones­
Price,
Ledoux,
Reel,
et
al.
1983)
based
on
a
significant
reduction
from
the
control
in
mean
fetal
body
weight/
litter
at
the
LOAEL
of
120
mg/
kg/
day.
Effects
observed
in
the
Narotsky
and
Kavlock
study
(
1995,
described
above
in
the
developmental
toxicity
conclusions
section)
at
53
mg/
kg/
day
provide
support
for
the
selection
of
the
60
mg/
kg/
day
as
an
endpoint
value.

Comments:
A
dermal
absorption
factor
of
50%
should
be
used
since
an
oral
endpoint
was
selected.
An
uncertainty
factor
of
100
is
employed
for
this
risk
assessment
(
10x
interspecies
extrapolation,
10x
intraspecies
variation)
12
6.
Dermal
Exposure:
Long­
term
The
volatile
nature
of
phenol
along
with
the
short
half­
life
of
the
chemical
is
not
expected
to
result
in
chronic
dermal
exposure
to
the
chemical.
Therefore,
the
ADTC
did
not
select
a
long­
term
dermal
endpoint
for
the
chemical
and
this
risk
assessment
is
not
required.

7.
Inhalation
Exposure
(
All
durations)

Study
Selected:
Dalin
and
Kristofferson:
Physiological
Effects
of
a
Sub­
lethal
Concentration
of
Inhaled
Phenol
on
the
Rat.
Ann.
Zool.
Fennici
11:
193­
199,
1974
Executive
Summary
(
from
the
IRIS
update):
In
a
study
published
by
Dalin
and
Kristoffersson
(
1974),
seven
white
rats
of
an
in­
house
strainwere
exposed
to
phenol
at
a
concentration
of
100
mg/
m3
continuously
for
15
days.
There
is
some
uncertainty
about
this
exposure
measure,
however,
because
the
exposure
chamber
was
not
set
up
according
to
modern
designs,
and
it
does
not
appear
that
continuous
monitoring
of
exposure
levels
was
conducted.
Unexposed
rats
(
n
=
11
B
12)
were
used
as
controls.
Nervous
system
effects
were
observed
from
the
first
day
after
the
start
of
exposure.
These
effects
progressed
from
increased
activity
to
imbalance,
twitches,
and
disordered
walking
rhythm
on
days
3
B
4.
These
signs
disappeared
by
day
5
and
were
replaced
by
sluggish
behavior
until
the
end
of
the
exposure.
A
tilting­
plane
test
was
conducted
before
and
after
exposure
in
both
groups,
and
a
significant
effect
was
observed
on
the
exposed
rats.
There
were
no
significant
changes
in
food
intake
or
water
consumption
during
the
exposure
period.
Although
there
was
no
significant
difference
in
body
weight
of
the
exposed
group
compared
with
that
of
the
controls,
the
average
body
weight
of
the
exposed
group
decreased
during
exposure,
whereas
the
controls
gained
weight.
The
serum
biochemical
evaluations
showed
large,
statistically
significant
increases
in
SGOT,
SGPT,
lactic
dehydroganese
(
LDH),
and
glutamate
dehydrogenase
activities,
indicating
liver
damage.

Plasma
potassium
and
magnesium
levels
were
also
increased.
Although
the
significance
of
these
changes
is
unknown,
the
authors
suggested
that
the
increased
magnesium
levels
may
have
caused
some
of
the
nervous
system
effects.
Hemoglobin
and
hematocrit
were
unaffected.
No
histopathology
examination
was
conducted.
On
the
basis
of
the
observed
nervous
system
effects
as
well
as
the
serum
enzyme
changes
indicating
liver
damage,
the
only
exposure
concentration
was
a
free­
standing
LOAEL.

Endpoint
used
for
risk
assessment:
LOAEL
of
0.1
mg/
L,
based
on
alterations
in
sliding
angle
from
tilting
plane
test,
and
significant
increases
in
liver
enzymes.
An
uncertainty
factor
of
300
is
applied
to
this
risk
13
assessment
for
short­
and
intermediate­
term
risk
assessments
(
10x
interspecies
extrapolation,
10x
intraspecies
variation,
3x
for
use
of
a
LOAEL).
For
long­
term
risk
assessments,
an
uncertainty
factor
of
1000
is
applied
to
the
risk
assessment
(
10x
interspecies
extrapolation,
10x
intraspecies
variation,
3x
for
use
of
a
LOAEL,
3x
for
lack
of
a
long­
term
study).
The
IRIS
Toxicological
review
also
notes
that
an
adequate
subchronic
inhalation
toxicity
study
for
phenol
is
not
available.

CLASSIFICATION
OF
CARCINOGENIC
POTENTIAL
The
updated
toxicological
review
in
the
EPA
IRIS
database
(
USEPA,
2002)
provides
a
summary
of
the
weight
of
the
evidence
with
respect
to
the
carcinogenic
potential
of
phenol,
and
this
is
reproduced
in
part
below.

Chronic
drinking
water
bioassays
of
phenol
have
been
conducted
in
rats
and
mice
(
NCI,
1980).
In
these
studies,
NCI
concluded
that
phenol
was
"
not
carcinogenic"
in
male
or
female
F344rats
or
B6C3F1
mice.
However,
the
report
also
noted
that
leukemia
and
lymphoma
were
statistically
significantly
increased
in
low­
dose
male
rats,
although
there
was
no
significant
increase
at
the
high
dose.
The
increases
in
leukemia
are
of
particular
interest
in
light
of
the
leukemogenic
effects
of
benzene
(
for
which
phenol
is
a
metabolite)
in
humans.
(
In
experimental
animals,
benzene
has
not
been
shown
to
induce
leukemia,
although
increases
in
lymphoma
have
been
observed
[
e.
g.,
NTP,
1986].).

In
contrast
with
the
negative
results
for
oral
carcinogenicity,
dermally
administered
phenol
has
been
consistently
observed
to
be
a
promoter.
Several
authors
(
Salaman
and
Glendenning,
1957;
Boutwell
and
Bosch,
1959;
Wynder
and
Hoffmann,
1961)
observed
that
dermally
applied
phenol
promoted
DMBA­
initiated
skin
tumors.
These
studies
have
generally
reported
significant
skin
ulceration
at
all
phenol
doses
tested.
The
exception
is
Wynder
and
Hoffman
(
1961),
who
reported
that
5%
phenol
promoted
DMBA­
initiated
tumors
in
mice
in
the
absence
of
any
toxic
reactions.
When
the
same
phenol
dose
was
administered
in
different
volumes,
higher
promotion
activity
was
exhibited
by
the
more
concentrated
solution,
which
also
produced
severe
skin
ulceration,
suggesting
that
some
of
the
promotion
activity
may
have
been
related
to
the
rapid
cell
division
of
repair
of
skin
damage
(
Salaman
and
Glendenning,
1957).

A
more
recent
study
of
the
tumor
promoting
ability
of
phenol
was
conducted
by
Spalding
et
al.
(
1993).
In
this
study,
a
transgenic
mouse
line
having
the
properties
of
genetically
initiated
skin
and
sensitive
to
TPA,
a
well
described
promotor
of
skin
papillomas
in
two­
stage
models,
were
treated
topically
2
times
per
week
for
up
to
20
weeks
with
several
chemicals
including
phenol.
Papillomas
were
induced
with
the
chemicals
benzoyl
peroxide,
TPA,
and
2­
butanol
peroxide.
Three
mg
of
phenol
administered
for
20
weeks
resulted
in
a
single
papilloma
in
one
of
five
male
mice
at
7
weeks
and
persisted
over
the
20
week
treatment
period.
This
response
was
not
statistically
significant
compared
to
controls.

A
mechanistic
study
conducted
by
Stenius
et
al.
(
1989)
was
designed
to
assess
the
toxicity
and
carcinogenicity
of
phenol
when
administered
to
partially
hepatectomized
male
SD­
rats.
Phenol
was
administered
by
gavage
5
days/
week
for
7
weeks
at
a
concentration
of
100
mg/
kg/
day.
Animals
were
sacrificed,
by
decapitation,
1
week
after
last
treatment.
Sections
of
the
rat
liver
were
prepared
and
stained
to
measure
for
induction
of
 ­
glutamyltranspeptidase
(
GGT)
positive
enzyme­
altered
foci
as
an
14
indicator
of
tumor
initiation.
Additional
studies
involved
single
oral
administrations
of
phenol
to
measure
inductions
of
hepatic
ornithine
decarboxylase
(
ODC),
glutathione
(
GSH)
depletion,
and
in
vivo
lipid
peroxidation.

Phenol
did
not
increase
the
number
or
volume
of
foci
and
was
found
to
have
no
tumor­
initiating
properties
within
the
confines
of
this
study.
Lipid
peroxidation
was
not
induced
following
administration
of
phenol
as
measured
by
malondialdehyde
(
MDA)
in
the
urine.
There
were
small
and
inconsistent
effects
observed
in
hepatic
ornithine
decarboxylase
(
ODC)
in
which
there
was
an
increase
at
the
middose
but
a
decrease
at
the
high­
dose.
Observed
measurements
of
hepatic
ODC
were
18.8,
32.3,
and
11.4
pmol/
mg/
h
for
the
phenol
doses
of
0,
50,
and
100
mg/
kg/
day,
respectively.
Phenol
did
not
induce
GSH
depletion
in
hepatocytes.

MUTAGENICITY
A
summary
of
mutagenicity
studies
conducted
with
phenol
is
shown
below.

Study
Type
Results
Bacterial
reverse
mutation
(
Ames
test).
Toxicology
18:
219­
232
Negative.
There
was
no
evidence
of
induced
mutant
colonies
over
background.
Positive
controls
produced
the
appropriate
responses
in
the
corresponding
strains
of
the
bacterial
reverse
mutagenesis
test.

Bacterial
reverse
mutation
(
Ames
test).
Env.
Mutagenesis
1:
3­
142
Negative.
There
was
no
evidence
of
induced
mutant
colonies
over
background.
Positive
controls
produced
appropriate
responses
in
corresponding
strains
of
the
bacterial
reverse
mutagenesis
test.

Bacterial
reverse
mutation
(
Ames
test).
Mutation
Res.
90:
91­
109
Negative.
No
evidence
of
induced
mutant
colonies
over
background
following
administration
of
phenol
in
the
absence
of
metabolic
activation.
Mutant
colonies
increased
following
treatment
with
phenol
in
the
presence
of
metabolic
activation.
Phenol
was
not
mutagenic
in
the
bacterial
strains
in
the
absence
of
metabolic
activation.
Phenol
showed
mutagenic
effects
as
measured
by
a
significant
increase
over
control
in
histidine
revertants
,
in
the
presence
of
metabolic
activation,
predominantly
in
the
Ames
tester
strains
of
S.
typhimurium
that
are
sensitive
for
frameshift
mutatgens
(
ie.,
TA
98)

Bacterial
reverse
mutation
(
Ames
test).
Food
Chemistry
and
Toxicology
20:
383­
391
Negative.
Phenol
did
not
significantly
induce
mutant
colonies
over
background.
The
number
of
histidine
revertants
scored
in
the
presence
of
phenol
never
more
than
slightly
exceeded
the
number
of
spontaneously
arising
revertants.

Bacterial
reverse
mutation
(
E
coli).
Mutation
Res.
105:
309­
312
Negative.
No
evidence
of
mutagenicity
based
on
results
that
phenol
did
not
induce
filamentation
in
the
E.
coli
Ion

strain.
15
In
vivo
gene
mutation
assay
(
Drosophila).
Mutation
Res.
90:
91­
109
Negative.
Phenol
was
administered
to
D.
melanogaster
and
3543,
3458,
and
2139
chromosomes
were
tested
for
sex­
linked
recessive
lethals
in
Broods
1,
2,
and
3,
respectively.
There
were
no
significant
increases
in
recessive
lethals
observed
following
administration
of
phenol
to
Broods
1,
2,
and
3
and
only
17
(
0.48%),
6
(
0.17%),
and
7
(
0.33%)
sex­
linked
recessive
lethals,
respectively,
were
measured
in
the
chromosomes
tested.
Although
the
frequency
of
recessive
lethals
was
increased,
these
changes
did
not
achieve
statistical
significance.
Phenol
was
not
mutagenic
within
the
confines
of
this
study.

In
vivo
gene
mutation
assay
(
Drosophila).
Env.
Mutagenesis
7:
677­
702
Negative.
Phenol
was
tested
up
to
cytotoxic
concentrations
2000
and
5250
ppm
in
feeding
and
injection
studies,
respectively.
The
number
of
sex­
linked
recessive
lethal
mutations
in
the
feeding
study
were
7
and
11
at
the
0
and
2000
ppm
doses,
respectively.
The
injection
assay
resulted
in
5
(
0
ppm)
and
6
(
5250
ppm)
sex­
linked
recessive
lethal
mutations,
while
the
feeding
study
exhibited
0.12
(
0
ppm)
and
0.17
(
2000
ppm)
lethals.
These
sex­
linked
recessive
lethal
mutations
were
not
significantly
different
from
those
found
in
controls.

In
vitro
mammalian
cells
in
culture
(
L5178Y).
Mutation
Res.
104:
389­
393
Positive.
Phenol,
in
ethanol,
was
administered
to
CHO
V79
cells
individually
at
concentrations
of
0,
25,
50,
100,
250,
or
500
µ
g/
mL
and
in
a
mixture
with
12
µ
g/
mL
of
benzo[
a]
pyrene
at
concentrations
of
100,
250,
or
500
µ
g/
mL
for
2
hours.
Evidence
of
mutagenicity
was
exhibited
by
the
statistically
significant
increase
in
the
frequency
of
8­
azaguanine
resistant
mutants
over
the
spontaneous
level
at
phenol
concentrations
of
250
and
500
µ
g/
mL
In
vitro
chromosome
aberration.
Cancer
Res.
53:
1023­
1026
Positive.
Phenol
was
administered
to
preincubated
HL60
cell
cultures.
The
cells
were
exposed
to
phenol
for
30
minutes
at
a
concentration
of
100
µ
M.
Phenol
at
a
concentration
of
100
µ
M
produced
a
3.5
fold
increase
of
8OHdGua
levels
in
DNA
in
HL60
cells
after
30
minutes
of
incubation.
Phenol
induced
rapid
8OHdGua
formation
in
HL60
cells
that
returned
to
normal
levels
following
further
incubation
presumably
due
to
the
rapid
repair
of
DNA
damage
Spermatogonial
chromosome
aberration
assay.
Folia
Morphology
36:
13­
22.
Positive.
Structural
aberrations
in
chromosomes
of
reproductive
cells
of
male
and
female
mice
of
the
Porton
strain
were
investigated
using
phenol.
Phenol
was
mutagenic
in
the
Porton
strain
mice
due
to
the
evidence
of
a
concentration­
related
(
0.08­
8.0
mg/
L/
day)
positive
response
of
spermatogonial
chromosome
aberrations
following
30
days
of
exposure
to
phenol
in
water.

Micronucleus
assay
in
mouse
bone
marrow.
Mutation
res.
244:
15­
20
Negative.
Mutagenicity
of
individual
and
combined
administrations
of
phenol
and
hydroquinone
were
investigated
by
examining
the
induction
of
micronucleated
polychromatic
erythrocytes
(
MNPCEs)
in
Swiss
CD­
1
male
mice
bone
marrow
cells.
The
administration
of
phenol
at
concentrations
40­
160
mg/
kg
bw
did
not
result
in
micronuclei
induction
in
the
mouse
bone
marrow
cells;
therefore,
phenol
was
not
genotoxic
in
this
assay.
16
DATA
GAPS
/
REQUIREMENTS
The
toxicity
data
base
for
Phenol/
Sodium
Phenate
is
considered
complete
and
there
are
no
toxicology
data
gaps
for
this
active
ingredient.
17
ACUTE
TOXICITY
The
acute
toxicity
of
phenol
had
been
described
in
the
open
scientific
literature
and
from
studies
submitted
to
the
Office
of
Toxic
Substances.

The
acute
oral
toxicity
of
phenol
has
been
described
in
IRIS
as
varying
widely,
from
doses
of
14
mg/
kg
to
930
mg/
kg
(
USEPA,
2002).
Data
assembled
by
the
Antimicrobials
Division
shows
oral
LD
50
values
in
the
range
of
297­
1120
mg/
kg,
which
corrorborates
to
some
extent
the
results
reported
in
IRIS.
Acute
dermal
toxicity
of
phenol
as
reported
in
IRIS
showed
a
dermal
LD
50
of
669.4
mg/
kg
from
application
of
undiluted
phenol
for
24
hours
to
the
skin
of
rats
(
Conning
and
Hayes,
1970).
Decreasing
the
concentration
of
phenol
appears
to
result
in
higher
dermal
LD
50
values;
for
example,
application
of
a
50%
aqueous
solution
showed
an
LD
50
value
of
2350
mg/
kg
(
OTS
#
0515564/
86­
070001402).
Data
on
acute
inhalation
toxicity
of
phenol
are
limited.
In
a
study
submitted
to
OTS
(
OTS#
0515567/
86­
870001405),
rats
were
exposed
for
8
hours
to
2.5
L/
min
of
100%
phenol,
with
no
mortality
reported.
In
a
two
week
inhalation
toxicity
study,
neurotoxicity
was
observed
at
a
concentration
of
0.1
mg/
L
but
no
mortality
was
observed.

Phenol
has
been
shown
to
be
a
significant
eye
and
skin
irritant.
In
a
study
submitted
to
OTS
(
OTS
#
0515567/
86­
870001405),
severe
damage
to
the
cornea
was
observed
after
instillation
of
a
15%
and
5%
solution
of
100%
phenol
into
the
eyes
of
rats.
In
another
study
(
Flickinger,
1976),
instillation
of
0.1g
phenol
into
the
eye
of
male
rats
produced
inflammation
of
the
conjunctiva,
corneal
opacity,
with
no
improvement
over
14
days
post­
dose.
Primary
dermal
irritation
studies
submitted
to
OTS
(
OTS
#'
s
0515564/
86­
070001402
and
0515567/
86­
870001405)
showed
mild
to
marked
erythema.
The
only
dermal
sensitization
study
was
performed
with
Happy
Jack
Mange
medicine
where
the
%
a.
i.
was
not
reported,
but
results
indicated
strong
sensitization
(
HED
document
#
010599).

Acute
Toxicity
Profile
for
Phenol/
Sodium
Phenate
Guideline
Number
Study
Type/
Test
substance
(%
a.
i.)
MRID
Number/
Citation
Results
Toxicity
Category
870.1100
(
§
81­
1)
Acute
Oral­
Rat
Phenol
purity
>
99%
Berman,
et
al.
1994
LD50
=
400
(
297­
539)
mg/
kg/
day
II
870.110
(
§
81­
1)
Acute
Oral
­
Rat
Phenol
purity
100%
OTS
#
­
0515567
86­
870001405
LD50
=
1030
(
940­
1120)
mg/
kg/
day
III
870.1100
(
§
81­
1)
Acute
Oral­
Rat
Phenol
purity
not
reported
Flickinger.
1976
LD50
=
650
(
490­
860)
mg/
kg/
day
III
870.1200
(
§
81­
2)
Acute
Dermal­
Rat
Phenol
purity
not
reported
Brown,
et
al.
1975
LD50
(
Non­
occluded)
=
0.68
(
0.57­
0.78)
mL/
kg
LD50
(
Occluded)
=
0.50
mL/
kg
II
Guideline
Number
Study
Type/
Test
substance
(%
a.
i.)
MRID
Number/
Citation
Results
Toxicity
Category
18
870.1200
(
§
81­
2)
Acute
Dermal­
Rabbit
Sodium
Phenate
purity
57%
OTS
#
­
0515564
86­
870001402
LD50
=
2350
(
1880­
2940)
mg/
kg/
day
III
870.1200
(
§
81­
2)
Acute
Dermal­
Rabbit
Phenol
purity
100%
OTS
#
­
0515567
86­
870001405
LD50
=
0.63
(
0.56­
0.70)
mL/
kg
II
870.1200
(
§
81­
2)
Acute
Dermal­
Rat
Phenol
purity
laboratory
reagent
grade
Conning,
et
al.
1970
LD50
=
669.4
mg/
kg/
day
II
870.1200
(
§
81­
2)
Acute
Dermal­
Rabbit
Phenol
purity
not
reported
Flickinger.
1976
LD50
=
850
(
600­
1200)
mg/
kg/
day
II
870.1300
(
§
81­
3)
Acute
Inhalation­
Rat
Phenol
purity
100%
OTS
#
­
0515567
86­
870001405
No
deaths
occurred
at
2.5
L/
min
for
8
hours
Not
established
870.1300
(
§
81­
3)
Acute
Inhalation­
Rat
Phenol
purity
not
reported
Flickinger.
1976
No
deaths
occurred
at
900
mg/
m3
for
8
hours
Irritation
and
timerelated
CNS
effects
Not
established
870.2400
(
§
81­
4)
Acute
Eye
Irritation­
Rabbit
Sodium
Phenate
purity
57%
OTS
#
­
0515564
86­
870001402
15%
solution
caused
corneal
necrosis
and
conjunctiva
lesions
II
870.2400
(
§
81­
4)
Acute
Eye
Irritation­
Rabbit
Phenol
purity
100%
OTS
#
­
0515567
86­
870001405
Severe
damage
to
the
cornea
at
15%
and
lesser
damage
in
5%
Not
established
870.2400
(
§
81­
4)
Acute
Eye
Irritation­
Rabbit
Phenol
purity
not
reported
Flickinger.
1976
Dose
not
provided.
Severe
conjunctiva,
iritis,
corneal
opacities
and
ulcerations
with
no
improvement
after
14
day
observation
period.
I
870.2500
(
§
81­
5)
Acute
Dermal
Irritation­
Rabbit
Sodium
Phenate
purity
57%
OTS
#
­
0515564
86­
870001402
Mild
to
marked
erythema
and
marked
capillary
injection
were
observed
in
50%
of
animals
tested
II
870.2500
(
§
81­
5)
Acute
Dermal
Irritation­
Rabbit
Phenol
purity
100%
OTS
#
­
0515567
86­
870001405
10%
solution
caused
moderate
to
marked
erythema
Not
established
870.2500
(
§
81­
5)
Acute
Dermal
Irritation­
Rabbit
Phenol
purity
not
reported
Flickinger.
1976
Corrosive
I
19
VIII.
SUMMARY
OF
TOXICOLOGY
ENDPOINT
SELECTION
Summary
of
Toxicological
Dose
and
Endpoints
for
Phenol
Exposure
Scenario
Dose
(
mg/
kg/
day)
used
in
risk
assessment
UF
Special
FQPA
SF
and
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
Acute
Dietary
(
gen
population)
This
risk
assessment
is
not
required.

Acute
Dietary
(
females
13­
49)
This
risk
assessment
is
not
required.

Chronic
Dietary
(
all
populations)
NOAEL=
60
UF
=
100
Chronic
RfD
=
0.6
mg/
kg/
day
100X
Developmental
toxicity
study
in
rats
(
NTP,
1983)
Based
on
significant
reductions
from
the
control
in
mean
fetal
body
weight/
litter
at
120
mg/
kg/
day.

Incidental
Oral
Short­
Term
(
1
­
30
Days)

Residential
Only
NOAEL=
60
mg/
kg/
day
MOE
=
100
Developmental
toxicity
study
in
rats
(
NTP,
1983)
Based
on
significant
reductions
from
the
control
in
mean
fetal
body
weight/
litter
at
120
mg/
kg/
day.

Incidental
Oral
Intermediate­
Term
(
1
­
6
Months)

Residential
Only
NOAEL=
60
mg/
kg/
day
MOE
=
100
Developmental
toxicity
study
in
rats
(
NTP,
1983)
Based
on
significant
reductions
from
the
control
in
mean
fetal
body
weight/
litter
at
120
mg/
kg/
day.

Dermal1
Short
and
intermediate­
term
NOAEL
=
60
mg/
kg/
day
MOE
=
100
Developmental
toxicity
study
in
rats
(
NTP,
1983).
Based
on
significant
reductions
from
the
control
in
mean
fetal
body
weight/
litter
at
120
mg/
kg/
day.

Inhalation2
All
durations
LOAEL
=
0.1
mg/
L
MOE
=
300
(
ST,
IT)

MOE
=
1000
(
LT)
Dalin
and
Kristofferson:
Physiological
Effects
of
a
Sub­
lethal
Concentration
of
Inhaled
Phenol
on
the
Rat.
Ann.
Zool.
Fennici
11:
193­
199,
1974
LOAEL
of
0.1
mg/
L,
based
on
alterations
in
sliding
angle
from
tilting
plane
test,
and
significant
increases
in
liver
enzymes
Cancer
data
inadequate
for
assessment
of
human
carcinogenic
potential
(
USEPA,
2002)

1a
dermal
absorption
factor
of
50%
should
be
used
since
an
oral
endpoint
was
selected.
