Document ID: EPA-HQ-OPP-2006-0156-0003
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-04-19T04:00Z

1
of
42
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
TXR
No.

Date:
March
23,
2006
MEMORANDUM
SUBJECT:
Alkylbenzene
Sulfonates
(
ABS)
Toxicology
Chapter
for
the
Reregistration
Eligibility
Decision
(
RED)
Document.
PC
Code:
079010,
190116
and
098002.
Case
No.
4006.
DP
Barcode:
D327886.

FROM:
Ayaad
Assaad,
D.
V.
M.,
PhD.
Toxicologist
And
William
Dykstra,
PhD.,
Toxicologist
Health
Effects
Division
(
HED)
(
7509C)

THRU:
Alberto
Protzel,
Ph.
D.
Senior
Branch
Scientist,
Tox
Branch
Health
Effects
Division
(
HED)
(
7509
C)

TO:
Deborah
Smegal,
MPH,
Toxicologist/
Risk
Assessor
Health
Effects
Division
(
HED)
(
7509
C)

Attached
is
the
Toxicology
Disciplinary
Chapter
for
the
Alkylbenzene
Sulfonates
(
ABS)
for
the
purpose
of
issuing
a
Reregistration
Eligibility
Decision
(
RED)
Document.
2
of
42
SODIUM
DODECYLBENZENE
SULFONATE
DODECYL
BENZENESULFONIC
ACID
BENZENE
SULFONIC
ACIDS,
C10­
16
ALKYL
DERIVS.
PC
Code:
079010,
098002,
190116
Toxicology
Disciplinary
Chapter
for
the
Re­
registration
Eligibility
Decision
(
RED)
Document
Prepared
by:
Ayaad
Assaad,
D.
V.
M.,
Ph.
D.
Toxicology
Branch/
HED
and
William
Dykstra,
Ph.
D.
RAB
1
Branch/
HED
And
Louis
Scarano,
Ph.
D.
Toxicology
Branch/
HED
3
of
42
TABLE
OF
CONTENTS
1.0
HAZARD
CHARACTERIZATION.............................................................................
4
2.0
REQUIREMENTS
........................................................................................................
7
3.0
DATA
GAP(
S)
...............................................................................................................
8
4.0
HAZARD
ASSESSMENT.............................................................................................
8
4.1
Acute
Toxicity............................................................................................................
8
4.2
Subchronic
Toxicity...................................................................................................
8
4.3
Prenatal
Developmental
Toxicity............................................................................
11
4.4
Reproductive
Toxicity
.............................................................................................
13
4.5
Chronic
Toxicity
......................................................................................................
14
4.6
Carcinogenicity........................................................................................................
15
4.7
Mutagenicity
............................................................................................................
17
4.8
Neurotoxicity
...........................................................................................................
17
4.9
Metabolism
..............................................................................................................
18
5.0
TOXICITY
ENDPOINT
SELECTION......................................................................
19
5.2
Dermal
Absorption..................................................................................................
19
5.3
Classification
of
Carcinogenic
Potential                 
20
6.0
FQPA
CONSIDERATIONS                      ...
20
6.1
Special
Sensitivity
to
Infants
and
Children
............................................................
20
6.2
Recommendation
for
a
Developmental
Neurotoxicity
Study.................................
21
8.0
REFERENCES............................................................................................................
21
9.0
APPENDICES
.............................................................................................................
24
9.1
Toxicity
Profile
Summary
Tables
...........................................................................
25
9.1.1
Acute
Toxicity
Table
...............................................................................................
25
9.1.2
Subchronic,
Chronic
and
Other
Toxicity
Tables
...................................................
25
4
of
42
1.0
HAZARD
CHARACTERIZATION
Linear
alkylbenzene
Sulfonate
(
LAS)
is
an
anionic
surfactant
which
was
introduced
in
1964
as
a
more
biodegradable
replacement
for
highly
branched
alkylbenzene
Sulfonates
(
ABS).
LAS
is
a
mixture
of
closely
related
isomers
and
homologues,
each
containing
an
aromatic
ring
Sulfonated
at
the
para
position
and
attached
to
a
linear
alkyl
chain.
Their
primary
use
is
as
a
detergent
for
cleaning
(
residential,
commercial,
and
on
surfaces
where
food
contact
occurs).
The
presence
of
LAS
in
many
commonly
used
household
detergents
gives
rise
to
a
variety
of
possible
consumer
contact
scenarios
such
as:
direct
and
indirect
skin
contact,
inhalation,
and
oral
ingestion
derived
either
from
residues
deposited
on
dishes,
from
accidental
product
ingestion,
or
indirectly
from
drinking
water.

In
addition
to
EPA
Office
of
Pesticide
Programs
reviews,
this
toxicology
chapter
draws
heavily
from
the
following
sources:
WHO
(
1996);
and
HERA
(
2004).
The
toxicology
database
consists
almost
entirely
of
published
literature,
is
essentially
complete
and
of
acceptable
quality
to
assess
the
potential
hazard
to
humans.

LAS
are
readily
absorbed
following
oral
ingestion,
but
not
following
dermal
exposure.
LAS
are
readily
metabolized,
excreted
fairly
rapidly,
and
do
not
accumulate
in
tissues.
Available
acute
toxicity
data
show
that
LAS
are
not
highly
acutely
toxic
(
Categories
III­
IV),
are
irritating
to
the
eye
and
skin,
and
they
are
weak­
moderate
skin
sensitizers.
Subchronic
and
chronic
exposures
show
that
the
liver,
kidney
and
intestinal
tract
(
following
oral
exposures)
are
the
major
target
organs
of
toxicity.
Both
in
vitro
and
in
vivo
genotoxicity
data
show
that
LAS
are
not
toxic
to
the
gene
or
the
chromosome.
LAS
did
not
cause
reproductive
or
developmental
toxicity
in
acceptable
studies.
Early
(
pre­
GLP)
carcinogenicity
studies
indicate
that
LAS
is
not
likely
to
be
carcinogenic.

The
hazard
endpoints
chosen
for
use
in
this
risk
assessment
are:

 
Acute
dietary
endpoint
 
there
were
no
effects
attributable
to
a
single
dose
of
LAS
exposure
and
so
no
acute
dietary
endpoint
was
chosen.
 
Chronic
dietary
endpoint
and
short­
term
incidental
oral
endpoint
 
a
NOAEL
of
50
mg/
kg/
day
was
chosen
based
on
three
different
studies
(
see
below).
There
were
no
susceptibility
concerns
for
infants/
children
and
so
the
special
FQPA
factor
of
10x
may
be
removed
and
the
traditional
uncertainty
factors
of
10
(
intraspecies)
and
10
(
interspecies)
were
used
to
derive
a
chronic
RfD
of
0.5
mg/
kg/
day.
 
Short­,
intermediate­,
and
long­
term
inhalation
exposure
scenarios
 
a
NOAEL
of
1
mg/
m3
from
a
six
month
inhalation
study
in
monkeys.
The
level
of
concern
is
100
for
both
occupational
and
residential
exposure
scenarios.
 
Dermal
exposure
scenarios
 
quantification
of
dermal
risk
is
not
required
for
several
reasons
described
below
in
Section
5.2,
but
mainly
because
LAS
are
dermal
irritants
at
concentrations
greater
than
about
20%
and
thus
dermal
exposure
would
be
self­
limiting.
5
of
42
Following
is
a
brief
summary
of
the
hazard
assessment
for
LAS:

Absorption,
Distribution,
Metabolism,
Excretion
In
animal
tests
(
oral
 
monkeys,
pigs,
rats),
LAS
are
readily
absorbed
from
the
gastrointestinal
tract,
are
distributed
throughout
the
body,
and
are
extensively
metabolized.
Excretion
is
via
both
the
urine
and
feces.
Available
dermal
absorption
data
(
rats
and
guinea
pigs)
indicate
that
LAS
are
poorly
absorbed
from
the
skin,
although
prolonged
contact
may
lead
to
irritation
and
thus
compromise
the
skin
to
permit
more
absorption
(
WHO,
1996
and
HERA,
2004).

Acute
Toxicity
(
Including
Irritation,
Sensitization)
LAS
exhibit
a
wide
range
of
acute
toxicity
via
the
oral
route
in
rats
(
LD50s
of
404
 
1980
mg/
kg),
with
a
narrower
range
in
mice
(
LD50s
of
1259­
2300
mg/
kg).
This
spans
the
acute
oral
toxicity
categories
of
III­
IV.
LAS
are
classified
as
acute
toxicity
category
II
for
the
dermal
route
and
category
IV
(
least
toxic)
via
the
inhalation
route.

LAS
is
an
irritant
to
the
eye
(
category
I),
skin
(
category
II),
and
is
a
weak­
moderate
skin
sensitizer
(
category
III).

Repeated
Dose
Toxicity
(
Subchronic
and
Chronic)
There
have
been
many
oral
repeated
dose
studies
performed
with
LAS
ranging
from
a
28­
day
study
in
monkeys
to
nine
month
studies
conducted
with
rats
and
mice.
There
have
also
been
repeated
dose
dermal
(
guinea
pigs,
rabbits,
and
rats)
and
inhalation
studies
(
dogs
and
monkeys).
Collectively,
the
animal
data
suggest
that
the
liver,
kidney
and
caecum
(
for
oral
studies)
are
the
major
target
organs
for
toxicity.
The
liver
and
kidney
effects
were
dose
and
duration
related
in
that
mild
effects
(
organ
weight
changes
and
serum
enzyme/
clinical
chemistry
changes
indicative
of
mild
organ
effects)
were
seen
at
lower
doses,
but
increased
in
severity
with
both
dose
and
time.

For
the
purposes
of
this
hazard
assessment,
several
studies
were
considered
collectively
to
determine
a
NOAEL
of
50
mg/
kg/
day
for
the
chronic
dietary
endpoint.
This
is
based
on:
increased
caecum
weight
and
slight
kidney
damage
(
at
a
LOAEL
of
114
mg/
kg/
d
in
the
six
month
rat
study);
reduced
body
weight
in
21­
day
old
pups
(
at
a
LOAEL
of
250
mg/
kg/
day
in
a
reproductive
toxicity
rat
study);
and
significant
decreases
in
renal
biochemical
parameters
(
at
a
LOAEL
of
145
mg/
kg/
day
in
a
nine
month
drinking
water
study
in
rats).

Developmental
Toxicity
A
number
of
developmental
studies
via
the
oral
and
dermal
routes
have
been
performed
with
LAS
in
rats,
mice
and
rabbits;
there
were
also
several
subcutaneous
injection
developmental
studies
reported
in
mice
(
WHO,
1996).
There
is
a
spectrum
of
quality
in
the
20+
studies
in
terms
of
dosing
(
some
had
only
one
or
two
doses),
purity
of
LAS
used
(
some
used
formulated
products
that
ranged
from
1­
45%
LAS
content),
and
overt
toxicity
to
the
pregnant
females
in
the
dermal
studies
due
to
severe
irritating
effects.
It
is
concluded
that
some
developmental
effects
(
including
some
terata)
were
observed
at
high
doses
at
which
maternal
toxicity
was
observed
and
the
available
information
does
not
suggest
any
qualitative
or
quantitative
susceptibility
differences
between
pups
and
pregnant
animals.
6
of
42
Reproductive
Toxicity
LAS
were
tested
in
several
multigeneration
studies
in
rats.
There
were
no
effects
on
reproductive
parameters
in
any
of
these
tests
at
doses
up
to
250
mg/
kg/
day.

Carcinogenicity
The
available
long­
term
studies
that
assessed
carcinogenicity
were
older
studies
(
pre­
1970)
that
would
not
be
acceptable
under
current
standards
(
due
to
low
number
of
animals
used,
insufficient
number
of
doses
and
extent
of
dosing,
and
limited
histopathological
examinations.
However,
the
limited
studies
provide
no
evidence
of
carcinogenicity
in
animals
given
LAS
orally.

Genotoxicity
The
toxicological
data
show
that
LAS
was
not
genotoxic
in
vitro
or
in
vivo.

Neurotoxicity
There's
no
evidence
in
the
literature
to
indicate
any
neurotoxic
effects
of
LAS
in
humans
or
laboratory
animal.
7
of
42
2.0
REQUIREMENTS
The
requirements
for
an
indirect
food
use
for
Linear
alkylbenzene
Sulfonate
(
LAS)
are
in
Table
1.

Table
1.
Technical
Test
Required
Satisfied
870.1100
........................................
Acute
Oral
Toxicity
870.1200
...................................
Acute
Dermal
Toxicity
870.1300
...............................
Acute
Inhalation
Toxicity
870.2400
.....................................
Primary
Eye
Irritation
870.2500
...............................
Primary
Dermal
Irritation
870.2600
......................................
Dermal
Sensitization
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
870.3100
................................
Oral
Subchronic
(
rodent)
870.3150
..........................
Oral
Subchronic
(
nonrodent)
870.3200
...............................................
28­
Day
Dermal
870.3250
...............................................
90­
Day
Dermal
870.3465
..........................................
90­
Day
Inhalation
yes
no
no
no
no
yes
yes
yes
­­
yes
870.3700a
..................
Developmental
Toxicity
(
rodent)
870.3700b
............
Developmental
Toxicity
(
nonrodent)
870.3800
..................................................
Reproduction
Yes
no
no
yes
yes
yes
870.4100a
.............................
Chronic
Toxicity
(
rodent)
870.4100b
.......................
Chronic
Toxicity
(
nonrodent)
870.4200a
........................................
Oncogenicity
(
rat)
870.4200b
..................................
Oncogenicity
(
mouse)
870.4300
....................................
Chronic/
Oncogenicity
No
no
no
no
no
yes
­­
yes
­­
­­

870.5100
.......
Mutagenicity 
Gene
Mutation
­
bacterial
870.5300..
Mutagenicity 
Gene
Mutation
­
mammalian
870.5375
........
Mutagenicity 
Structural
Chromosomal
Aberrations
870.5xxx
.........
Mutagenicity 
Other
Genotoxic
Effects
Yes
Yes
Yes
No
yes
yes
yes
­­

870.6100a
....................
Acute
Delayed
Neurotox.
(
hen)
...................................................................
870.6100b
..........................
90­
Day
Neurotoxicity
(
hen)
870.6200a
.......
Acute
Neurotox.
Screening
Battery
(
rat)
870.6200b
.........
90
Day
Neuro.
Screening
Battery
(
rat)
870.6300
..............................................
Develop.
Neuro
No
no
no
no
no
no
­
­
­
­
­
­

870.7485
.......................................
General
Metabolism
870.7600
.........................................
Dermal
Penetration
No
No
Yes
­

Special
Studies
for
Ocular
Effects
Acute
Oral
(
rat)............................................................
Subchronic
Oral
(
rat)....................................................
Six­
month
Oral
(
dog)
...................................................
No
no
no
no
­
­
­
­
8
of
42
3.0
DATA
GAP(
S)

Based
on
the
non­
food
use
of
linear
alkylbenzene
Sulfonate
(
LAS),
as
well
as
the
limited
use
as
a
house
hold
detergent,
the
database
appears
to
be
adequate,
unless
other
uses
are
needed.

4.0
HAZARD
ASSESSMENT
4.1
Acute
Toxicity
Adequacy
of
data
base
for
acute
toxicity:
The
data
base
for
acute
toxicity
is
considered
complete.
No
additional
studies
are
required
at
this
time.
The
acute
toxicity
data
on
the
Linear
alkylbenzene
Sulfonate
(
LAS)
Technical
is
summarized
below
in
Table
2.

Table
2.
Acute
Toxicity
Data
on
Linear
alkylbenzene
Sulfonate
(
LAS):

Guideline
No./
Study
Type
MRID
No.
Results
Toxicity
Category
870.1100
Acute
oral
toxicity
Multiple
LD50
=
range
from
404
to
over
5000
mg/
kg
III­
IV
870.1200
Acute
dermal
toxicity
94032006
LD50
=
1200
mg/
kg
II
870.1300
Acute
inhalation
toxicity
003442*
LC50
=
200
mg/
L
IV
870.2400
Acute
eye
irritation
0033443*
Corneal
opacity
not
reversed
at
72
hours.
I
870.2500
Acute
dermal
irritation
003444*
Severe
irritation
at
72
hours
II
870.2600
Skin
sensitization
Open
Literature
{
Nusair
TL,
PJ
Danneman,
J
Stotte,
PHS
Bay
(
1988)
Consumer
Products:
Risk
Assessment
Process
for
Contact
Sensitization,
Toxicologist
8:
258.
(
HERA)}
Weak
to
moderate
sensitization
*
Tox
record
No.

4.2
Subchronic
Toxicity
Adequacy
of
data
base
for
subchronic
toxicity:
The
data
base
for
subchronic
toxicity
is
considered
complete.
No
additional
studies
are
required
at
this
time.
The
major
reviews
by
the
WHO
(
1996),
and
HERA
(
2004)
report
and/
or
summarize
many
subchronic
studies
via
the
oral
(
gavage,
feed,
and
drinking
water),
dermal,
and
inhalation
routes.
Only
the
critical
studies
or
ones
for
which
OPP
has
developed
DERs
over
the
years
are
summarized
here.
9
of
42
870.3100
90­
Day
Oral
Toxicity
 
Rat
(
Ikawa
et
al.
1978;
as
cited
in
HERA,
2004).
LAS
was
administered
for
2,
4,
and
12
weeks
to
male
rats
(
5/
group)
at
a
single
dose
of
1.5%
in
the
diet
(
750
mg/
kg
bw/
day).
LAS
suppressed
body
weight
gain,
and
the
relative
liver
weight
was
increased
after
2
weeks
of
LAS
administration.
Serum
biochemical
examinations
revealed
significant
increases
in
ALP
and
GTP
at
each
observation
period
and
significant
decreases
in
cholesterol
and
protein
in
4
weeks.
Enzymatic
examinations
of
the
liver
revealed
decreases
in
G6Pase
and
G6PDH
and
an
increase
in
isocitrate
dehydrogenase
(
IDH)
at
each
observation
period.
Enzymatic
examinations
of
the
renal
cortex
revealed
decreases
in
G6Pase
and
5'­
nucleotidase
at
each
observation
period,
an
increase
in
LDH
at
12
weeks,
and
an
increase
in
IDH
at
2
and
4
weeks.
Enzymatic
examinations
in
the
renal
medulla
revealed
a
decrease
in
Na,
KATPase
and
an
increase
in
LDH
at
12
weeks,
a
decrease
in
IDH
at
2
weeks,
and
an
increase
in
IDH
at
12
weeks.

In
another
study
(
MRID
No.
43498412;
Kay
et
al.
(
1965)
as
cited
in
HERA,
2004),
LAS
(
87.9%
purity)
was
administered
in
the
diet
at
dietary
levels
of
0,
200,
1000,
and
5000
ppm
for
90
days
to
weanling
Sprague­
Dawley
Rat
(
10/
sex/
dose).

Body
weight
and
food
consumption
was
measured
pretest
and
weekly
on
all
animals
and
hematology
and
urine
analysis
were
done
on
5/
sex/
group
at
days
0,
30,
60,
and
90.
Clinical
chemistry
measurements
were
not
performed.
All
animals
were
sacrificed
by
ether
inhalation
and
subject
to
gross
necropsy.
Weights
of
liver,
kidneys,
spleen,
gonads,
heart
and
brain
were
taken
and
absolute
and
relative
(
both
body
and
brain)
organ
weights
were
calculated.
Histopathology
was
performed
on
5/
sex
from
control
and
high
dose
and
3/
sex
from
low
and
mid
dose
animals
from
25
organs
and
tissues.
Required
tissues
not
examined
were
aorta,
eyes,
cecum,
skin,
trachea,
sciatic
nerve,
esophagus,
rectum,
thymus,
mammary
gland,
epididymis,
spinal
cord,
and
salivary
glands.
Two
low
dose
males
died
early
in
the
study
from
respiratory
illness
There
was
no
compound­
related
effects
in
body
weight,
food
consumption,
hematology,
urine
analysis,
organ
weight,
and
histopathology.

Acceptable/
Guideline.

870.3101
90­
Day
Oral
Toxicity
­
Mouse
This
study
is
not
available
in
the
database
of
this
chemical;
however,
a
sub­
chronic
monkey
study
is
available
in
the
database.

Groups
of
3
male
and
3
female
Rhesus
monkeys
18­
36
months
old
and
weighing
2.0­
4.4
kg,
were
treated
simultaneously
with
SDDBS
(
LAS)
in
distilled
water
at
doses
of
0
(
controls),
30
mg/
kg
(
oral)
+
0.3.
mg/
kg
(
subcutaneous),
150
mg/
kg
(
oral)
+
0.5
mg/
kg
(
subcutaneous)
and
300
mg/
kg
(
oral)
+
1
mg/
mg
(
subcutaneous)
for
28
days
(
MRID
43498413).
Parameters
measured
were
body
weight,
ophthalmoscopy,
hematology,
clinical
chemistries,
urinalysis,
necropsy,
organ
weights,
and
histopathology.
NOEL
is
30
mg/
kg
(
p0)
+
0.1mg/
kg
(
sc).
Effects
seen
in
the
high
dose
were
emesis
(
vomiting)
and
liquid
feces.
Liquid
feces
were
also
seen
in
the
mid
dose.
10
of
42
All
treated
animals
had
fibrosis
at
the
subcutaneous
injection
site,
but
this
was
not
included
in
the
determination
of
a
NOEL
since
this
is
a
common
finding
for
tissue
irritants
and
not
an
indication
of
systemic
toxicity.

Core
Classification:
ACCEPTABLE
870.3150
90­
Day
Oral
Toxicity
­
Dog
This
study
is
not
available
in
the
database
of
this
chemical.

870.3200
21/
28­
Day
Dermal
Toxicity
 
Rat
This
study
is
not
available
in
the
database
of
this
chemical;
however,
there
were
a
28­
dermal
study
in
the
rabbit
(
Tox
record
No.
003441),
which
was
classified
as
"
unacceptable"
and
an
acceptable
30­
day
study
in
guinea
pigs
summarized
below.

Mathur
et
al.
(
1992).
J
Toxicol
Cutan
Ocular
Toxicol,
11(
1):
3­
13.
(
as
cited
in
WHO
1996).
A
solution
of
LAS
in
distilled
water
equivalent
to
60
mg/
kg
bw
was
applied
to
a
4­
cm2
area
of
clipped
dorsal
skin
daily
of
12
Guinea
Pigs
for
30
days.
The
activities
of
B­
glucuronidase,
gamma­
glutamyl
transpeptidase,
5­
nucleotidase,
and
sorbitol
dehydrogenase
were
increased
in
liver
and
kidney.
Lipid
peroxidation
was
increased
in
the
kidney
but
not
in
liver,
and
the
glutathione
content
was
unchanged
in
both
organs.
Extensive
fatty
changes
were
found
in
hepatic
lobules,
with
dilation
of
sinusoids;
tubular
lesions
were
found
in
the
kidney,
predominantly
in
the
proximal
and
distal
portions.

870.3465
90­
Day
Inhalation
 
Rat
This
study
is
not
available
in
the
database
of
this
chemical;
however,
there
is
an
acceptable
subchronic
monkey
inhalation
study.

In
a
subchronic
inhalation
toxicity
study
in
monkeys
(
MRID
43498403),
groups
of
5
male
and
4
female
cynomolgous
monkeys,
1.6
to
3.7
kg,
were
randomly
divided
into
12
nominal
groups
(
mg/
m3)
­
control,
detergent
(
D),
enzyme
(
E),
or
both
at
levels
at
0,
l00(
D)
and
(
0.001(
E),
0.01(
E),
0.1(
E)
and
1(
E))
together
with
[
0,
1(
D),
10(
D),
and
100(
D)]
for
6
hours
daily,
5
days
a
week
for
6
month.
Particle
analysis
and
gravimetric
determinations
showed
particle
size
to
have
a
MMD
and
gravimetric
concentrations
to
be
slightly
higher
than
nominal.
The
detergent
formulation
contained
13%
C12
linear
alkylbenzene
sulfonate
(
the
remaining
major
ingredients
were
sodium
tripolyphosphate
[
39%];
sodium
sulfate
[
40%];
and
sodium
silicate
[
7%]).

Routine
measurements
included
body
weight,
toxic
signs,
clinical
evaluation,
chest
radiograph,
tuberculin
skin
test,
pulmonary
function
tests
(
3
different
tests),
hematoloqy,
clinical
chemistry,
urinalysis,
intradermal
and
prick
test,
necropsy,
and
histopathology.
The
NOEL
is
1
mg/
m3
detergent
dust
combined
with
up
to
0.1
mg/
m3
enzyme
dust.
The
detergent
dust
at
100
mg/
m3
alone
and
with
enzyme
dust
produced
mortality
At
least
one
animal
in
each
group
exposed
to
enzyme
dust
had
precipitating
antibodies
to
the
enzyme.
There
were
no
effects
at
any
level
in
total
respiratory
system
flow
resistance,
diffusion
capacity,
hematology,
clinical
chemistry,
urinalysis,
intradermal
or
skin­
prick
challenge
test
results,
and
chest
X­
rays.
11
of
42
In
this
published
study,
the
detergent
was
dried
and
micronized
to
make
it
respirable.
However,
it
should
be
noticed
that
most
uses
of
this
detergent
are
in
liquid
form.
It
is
a
common
misconception
that
the
small
particle
size
used
in
an
animal
study
(
MMAD
of
1­
3
um
in
acute
studies,
1­
4
um
in
multiple
exposure
studies)
has
no
relevance
to
the
large
particle
size
that
comes
from
medium
to
coarse
powdered
material
or
a
liquid­
powder
mix
during
use.
Detergents
are
typically
mixed
with
large
quantities
of
water
before
use.
When
the
aqueous
mix
is
used,
droplets
rapidly
shrink
as
they
fall
due
to
water
evaporation.
The
degree
of
shrinkage
depends
on
temperature,
relative
humidity,
particle
size,
and
the
length
of
time
that
the
droplets
are
suspended
in
the
air.
Since
humans
are
capable
of
inhaling
particles
>
100
um,
it
is
reasonable
to
expect
a
significant
portion
of
these
particles
to
be
inhaled.
While
most
large
particles
are
captured
in
the
nose,
some
are
capable
of
reaching
the
lungs.
Large
particles
have
the
potential
to
do
considerable
local
damage
if
they
are
respirable
because
of
the
volume
of
material
they
contain.

Core
Classification:
ACCEPTABLE
4.3
Prenatal
Developmental
Toxicity
Adequacy
of
data
base
for
Prenatal
Developmental
Toxicity:
The
data
base
for
prenatal
developmental
toxicity
is
considered
complete.
There
are
many
developmental
studies
that
have
been
identified
and
reviewed
in
the
WHO
and
HERA
documents.
No
additional
studies
are
required
at
this
time.

870.3700a
Prenatal
Developmental
Toxicity
Study
 
Rat
Teratology
­
rat,
mouse,
rabbit,
MRID
NO.
43498426
("
Palmer
Part
I").
Randomized
groups
of
20
CD­
1
pregnant
mice,
20
CD
rats,
and
13
NZW
rabbits
were
housed
individually
and
fed
appropriate
diets
ad
libitum.
Day
0
of
gestation
was
judged
by
a
vaginal
plug
in
rats
and
mice
and
coitus
in
rabbits.
Dosing
began
on
day
6
and
continued
daily
up
to
day
15
for
mice
and
rats
and
day
18
for
rabbits.
The
test
material
was
supplied
by
Lion
fat
and
Oil
Co.,
Led,
Tokyo.
Doses
were
0,
0.2,
2.0,
300
and
600.
mg/
kg
BW.
Animals
were
observed
daily
and
weighed
regularly.
At
termination
(
Days
17,
20,
and
29
for
mice,
rats,
and
rabbits),
the
uteri
were
immediately
dissected
and
contents
examined
to
determine
implantations,
viable
young,
embryonic
deaths
(
abortion
or
resorption
sites).
Ovaries
were
examined
and
the
number
of
corpora
lutea
counted
for
rats
and
rabbits.
Fetuses
were
weighed
and
externally
examined
for
abnormalities.
With
rabbits,
the
fetuses
were
immediately
dissected
and
examined
for
visceral
abnormalities.
Sex
was
determined
by
gonadal
inspection
and
carcasses
preserved
in
alcohol
for
subsequent
clearing,
staining.
with
alizarin,
and
skeletal
examination.
With
mice
and
rats,
following
weighing
and
external
examination,
one
third
were
fixed
in
Baum's
solution
for
free
hand
sectioning
for
visceral
abnormalities
and
the
remaining
two­
thirds
fixed
in
alcohol,
cleared,
stained
with
alizarin
and
examined
skeletally.

In
assessing
results,
group
means
were
calculated
from
the
individual
litter
data
in
two
ways.
Mean
A:
includes
all
surviving
animals
showing
evidence
of
implantation,
including
those
with
12
of
42
total
litter
loss.
Mean
B:
includes
only
animals
bearing
viable
young
at
termination.
Mean
B
has
more
meaning
when
only
the
occasional
animal
shows
total
litter
loss
and
Mean
A
provides
a
better
index
when
several
animals
show
total
litter
loss.

Generally,
maternal
toxicity
ranked
rabbits
>
mice
>
rats.
In
all
species
tested,
toxic
reactions
involved
a
disturbance
of
the
gastrointestinal
tract.
Affected
rabbits
showed
diarrhea,
anorexia,
weight
loss
and
cachexia
prior
to
death.
Total
litter
loss
(
abortion
and/
or
total
resorptions)
tended
to
occur
as
a
result
of
maternal
toxicity.
The
NOEL
for
maternal
effects
is
2.0
mg/
kg
for
rabbits
and
mice,
and
300mg/
kg
for
rats.
At
doses
at
or
below
the
NOEL,
values
for
litter
size
and
fetal
loss
were
comparable
to
controls.

The
NOEL
for
developmental
toxicity
is
2.0
mg/
kg/
day
in
mice,
300
mg/
kg/
day
in
rats,
and
2.0mg/
kg/
day
in
rabbits.
Although
the
identity
of
the
malformations
and
anomalies
was
not
specified
in
the
report,
there
was
no
apparent
increase
in
numbers
of
malformation
at
any
dose
in
mice,
rats
and
rabbits.
Additionally,
mice
at
the
maternally
toxic
dose
of
300
mg/
kg/
day
had
increases
in
the
percent
of
minor
visceral
and
skeletal
anomalies.
Similarly,
in
rats,
at
the
maternally
toxic
dose
of
600
mg/
kg/
day,
there
was
an
increase
in
minor
visceral
anomalies.

Core
Classification:
ACCEPTABLE
Dermal
Developmental
Toxicity
 
Rat,
Rabbit,
Mouse
MRID:
43511403.
(
Palmer
Part
III).
The
surfactant
linear
alkylbenzene
Sulfonate
(
LAS)
was
examined
for
embryotoxic
and
teratogenic
potential
following
percutaneous
administration
(
MRID
43511403).
Solutions
containing,
0.03,
0.3
or
3%
LAS
were
applied
to
shaved
skin
during
pregnancy
days
2­
13
in
mice,
2­
15
in
rats
and
1­
16
in
rabbits.
Dosages
employed
were
0.5
mg/
rat
or
mouse/
day
and
10
mg/
rabbit/
day.
For
comparison,
further
groups
of
rats
and
mice
were
similarly
treated
with
concentrations
of
0.3,
3
and
30%
of
a
standard
soap
solution.

Marked
local
skin
reaction,
irritability,
weight
loss
and
failure
to
maintain
or
establish
pregnancy
was
evident
in
mice
treated
with
LAS
3%
soap,
3
or
30%:
marked
local
reaction
and
weight
loss
also
occurred
in
rabbits
receiving
LAS
3%.
Moderate
maternal
toxicity
was
observed
among
mice
treated
with
LAS,
0.3%
and
mild
maternal
toxicity
in
rats
receiving
LAS
3%
or
soap
30%
and
rabbits
receiving
LAS
0.3%.

Effects
on
litter
parameters
were
generally
restricted
to
dosages
causing
marked
maternal
toxicity
in
mice,
the
principal
effects
being
higher
fetal
loss
(
with
consequent
reduction
in
viable
litter
size)
arising
from
an
increased
incidence
of
total
litter
losses.
Although
LAS
at
3%
was
considered
to
show
marked
maternal
toxicity
in
the
rabbit,
the
slightly
higher
fetal
loss
and
lower
litter
size
did
not
differ
significantly
from
control
values.

The
moderate
maternal
toxicity
of
LAS,
0.3%
in
the
mouse
correlated
with
a
higher
incidence
of
embryonic
deaths
and
lower
litter
size
but
only
the
former
differed
significantly
from
the
corresponding
control
value.
13
of
42
The
incidences
of
major
malformations,
minor
visceral
or
skeletal
anomalies,
and
skeletal
variants
provided
no
conclusive
evidence
of
specific
teratogenicity
even
at
maternally
toxic
dosages.

The
LOEL
for
maternal
toxicity
was
0.3%
(
50.0
mg/
kg/
day),
3.0%
(
60.0
mg/
kg/
day)
and
0.3%
(
9.0
mg/
kg/
day)
LAS
in
mice,
rats
and
rabbits,
respectively.
The
NOEL
for
maternal
toxicity
was
0.03%
(
5.0
mg/
kg/
day):
0.3%
(
6.0
mg/
kg/
day)
and
0.03%
(
0.9
mg/
kg/
day)
LAS
in
mice,
rats
and
rabbits,
respectively.
The
LOEL
for
developmental
toxicity
was
0.3%
(
50.0
mg/
kg/
day),
3.0%
(
60.0
mg/
kg/
day)
and
3.0%
(
90.0
mg/
kg/
day),
respectively.
The
NOEL
for
developmental
toxicity
was
0.03%
(
5.0
mg/
kg/
day),
0.3%
(
6.0
mg/
kg/
day)
and
0.3%
(
9.0
mg/
kg/
day),
respectively.

The
study
is
supplementary
and
satisfies
the
guideline
requirement
for
a
series
83­
3
developmental
(
dermal)
toxicity
study.

Mouse­
Developmental
In
a
mouse
developmental
toxicity
study
(
MRID
43498424
&
43498425),
virgin
female
ICR/
Jc1
mice,
9­
10
weeks
old,
and
weighing
30­
32
grams,
were
used.
Mice
were
maintained
on
mouse
diet
CA­
1
and
tap
water
ad
libitum.
The
mice
were
exposed
to
light
to
induce
ovulation
and
were
mated
with
breeder
males.
The
presence
of
a
vaginal
plug
indicated
day
0.
On
day
0,
the
mother's
hair
was
plucked
from
a
2
x
3
cm
area
of
the
dorso­
thoracic
skin
and
0.1
ml
of
20%
aqueous
LAS
was
applied
to
the
skin
twice
a
day
from
day
0
to
day
3.
The
mice
were
sacrificed
on
day
3
and
oviducts
and
uterus
removed.

Embryos
were
flushed
from
the
oviducts
and
uterus
with
Whitten
medium.
After
examination,
the
embryos
were
then.
cultivated
at
37oC
in
medium
equilibrated
with
a
5%
carbon
dioxide,
5%
oxygen,
and
90%
nitrogen
gas
mixture.
A
2.0%
dermally
applied
dose
of
LAS
retarded
development
and
interrupted
cleavage
of
eggs.
Significantly
higher
numbers
of
embryos
were
found
to
be
deformed
in
the
LAS
group
in
comparison
to
controls,
and
most
of
these
embryos
were
in
the
morula
stage,
whereas
they
were
mostly
in
the
late
blastocyst
stage
in
controls.

Core
Classification:
ACCEPTABLE
870.3700b
Prenatal
Developmental
Toxicity
Study
 
Rabbit
This
study
is
included
with
section
870.3700a.

4.4
Reproductive
Toxicity
Adequacy
of
data
base
for
Reproductive
Toxicity:
The
data
base
for
reproductive
toxicity
is
considered
complete.
No
additional
studies
are
required
at
this
time.

870.3800
Reproduction
and
Fertility
Effects
 
Rat
14
of
42
In
a
reproduction
study
with
rats
(
MRID
43498416),
randomized
groups
of
20/
sex/
dose
weanling
Charles
River
CD
rats
(
the
P0
parental
animals)
were
fed
test
diets
containing
0,
0.02,
0.1,
and
0.5%
LAS
(
equivalent
to
0,
10,
50,
and
250
mg/
kg/
day)
for
84
days
(
at
which
time
they
were
107
­
112
days
old).
Rats
from
each
dose
group
were
mated
(
1:
1),
litters
allowed
to
be
delivered,
pups
counted
(
F1a),
and
examined,
culled
to
8/
litter
on
day
4,
and
sacrificed
at
day
21
of
lactation.
Pups
of
the
F1a
and
F2a
litters
were
both
sacrificed
after
day
21
of
lactation.
Ten
days
later,
the
rats
were
again
mated
to
produce
the
F1b
litters.
20/
sex/
dose
of
F1b
weanlings
were
selected
to
generate
the
P1
and
P2
parental
animals
for
generating
the
F2a,
F2b,
F3a
and
F3b
litters.

Food
consumption,
body
weight,
and
food
efficiency
were
recorded
weekly
for
the
first
8
weeks.
Five
male
and
5
female
rats
from
the
F1b
and
F2b
parental
groups
and
F3b
pups
were
selected
for
necropsy.
Body
weight,
organ
weights,
hematology,
and
histology
were
performed.

General
reproduction
including
fertility,
gestation,
parturition,
neonatal
viability,
lactation,
and
post­
weanling
growth
were
comparable
for
control
and
test
groups
and
no
gross
abnormalities
were
found.
There
were
comparable
results
in
body
weight,
food
consumption,
hematology
and
organ
weight
findings
between
control
and
treated
animals.
The
only
significant
finding
in
hematology,
was
in
the
0.5%
F2b
females,
whose
RBCs
count
was
depressed
significantly
(
15.4%)
but
was
within
the
range
of
historical
control
data.
The
only
histologic
lesion
of
possible
significance,
for
which
the
data
were
not
presented,
was
a
pancreatic
lesion
seen
in
F2b
males.
This
lesion
usually
consisted
of
acinar
atrophy
and
degeneration
accompanied
by
a
fibrous
tissue
replacement.
There
were
also
indications
of
mild
islet
cell
hyperplasia.
There
appeared
to
be
an
increased
incidence
of
the
general
lesion
in
animals
fed
0.5%
LAS.

The
NOEL
is
0.1%
or
1000
ppm
for
reproductive
toxicity
and
5000
ppm
(
HDT)
for
systemic
toxicity.
Based
on
the
reported
findings,
the
LEL
is
considered
to
be
0.5%.
due
to
histopathology,
hematology,
and
the
occasional
slightly
decreased
day
21
body
weights
in
female
pups.

Core
Classification:
ACCEPTABLE
4.5
Chronic
Toxicity
Adequacy
of
data
base
for
chronic
toxicity:
The
data
base
for
chronic
toxicity
is
considered
complete.
No
additional
studies
are
required
at
this
time.

LAS
was
administered
to
male/
female
rats
for
9
months
in
drinking
water,
at
doses
of
0.07%,
0.2%
and
0.6%
(
85,
145,
430
mg/
kg
bw/
day)
(
Yoneyama
et
al.,
1976
as
cited
in
HERA,
2004).
Control
groups
were
used.
Hematological
examination
revealed
no
significant
changes
in
any
experimental
group
and
no
organ
weight
changes
were
observed.
Body
weight
gain
was
suppressed
in
the
males
of
the
highest
dose
group
and
also
serum­
biochemical
and
enzymatic
parameters
of
the
liver
and
kidney
were
affected.
A
significant
decrease
in
renal
Na,
K­
ATPase
was
seen
in
the
group
given
145
mg/
kg
bw/
day
of
LAS.
The
NOAEL
is
85
mg/
kg
bw/
day
and
the
LOAEL
is
145
mg/
kg
bw/
day.
15
of
42
Groups
of
8
or
9
male/
females
mice
were
given
diets
containing
LAS
at
concentrations
of
0.6
and
1.8%
(
corresponding
to
500
and
1000
mg/
kg
bw/
day)
or
drinking
water
containing
LAS
at
concentrations
of
0.07%,
0.2%
and
0.6%
for
9
months
(
corresponding
to
100,
250,
600
mg/
kg
bw/
day
for
males
and
to
100,
250,
900
mg/
kg
bw/
day
for
females)
(
Yoneyama
et
al.,
1976
as
cited
in
HERA,
2004).
Control
groups
were
used.

In
the
mice
given
500
mg/
kg
bw/
day
via
the
food,
body
weight
gain
was
not
suppressed,
but
the
weight
of
the
liver
increased
in
male
and
female
mice.
Enzymatic
examinations
revealed
significant
decreases
in
LDH
of
the
liver
and
in
acid
phosphatase
of
the
kidneys
in
the
male
mice.
Thus,
there
was
no
NOAEL
in
this
study
since
these
effects
were
seen
at
the
lowest
dose
of
500
mg/
kg/
d.

In
the
drinking
water
study,
body
weight
was
depressed
at
the
highest
dose
for
male
and
females,
increase
in
liver
weight
in
females
and
significant
decreases
in
renal
Na,
K­
ATPase
resulted
in
a
LOAEL
of
600
mg/
kg/
d
(
males)
and
900
mg/
kg/
d
(
females)
with
a
NOAEL
of
250
mg/
kg
bw/
day.

In
a
third
study
by
the
same
authors
(
Yoneyama
et
al.,
1972
as
cited
in
HERA,
2004),
10
rats/
sex/
dose
were
given
the
following
doses
of
LAS
in
feed:
0,
0.07%,
0.2%,
0.6%,
and
1.8%
(
equivalent
to
0,
40,
115,
340,
and
1030
mg/
kg/
d).
The
following
effects
were
observed:
diarrhea
(
high
dose
group
only),
suppressed
growth
(
340
and
1030
mg/
kg/
d
dose
groups),
increases
cecum
weight
(
all
dose
groups
above
40
mg/
kg/
d),
and
renal
tubular
degeneration
(
all
dose
groups
above
40
mg/
kg/
d).
Thus,
the
NOAEL
is
40
mg/
kg/
d
with
a
LOAEL
of
115
mg/
kg/
d
for
increased
cecum
weight
and
slight
degeneration
of
renal
tubules.

870.4100b
Chronic
Toxicity
­
Dog
This
study
is
not
available
in
the
toxicology
database
of
this
chemical.

4.6
Carcinogenicity
Adequacy
of
data
base
for
Carcinogenicity:
The
data
base
for
carcinogenicity
is
considered
complete.
No
additional
studies
are
required
at
this
time.

870.4200a
Carcinogenicity
Study
 
rat
Takahasi
(
MRID
43498420)
performed
an
experiment
to
assess
the
ability
of
SDDBS
to
affect
the
induction
of
gastric
tumors
by
4­
NQO
in
male
Wistar
rats.
Sixty­
four
male
rats
of
the
Motoyania
strain
and
97
male
Wistar
rats
were
used
in
the
study
under
the
following
regimen:
Group
I
(
79
rats):
1
mg
4­
NQO
and
80
mg
SDDBS
2­
3
times
per
week
for
18
weeks
Group
1'
(
17
rats):
same
as
Group
I,
but
fasted
12
hours
prior
to
dosing
Group
II
(
37
rats):
4­
NQO
only
as
per
Group
`
1
Group
III
(
28
rats):
SDDBS
only
as
per
Group
I
16
of
42
The
experiment
lasted
560
days
and
all
rats
dying
on
study
or
terminally
sacrificed,
were
necropsied
and
examined
histologically
for
gastrointestinal
tumors.
In
Groups
I
and
I`,
the
presence
of
SDDBS­
shifts
the
incidence
of
benign
papillomas
to
malignant
papillomas
of
the
forestomach
and
the
incidence
of
adenocarcinoma
and
sarcoma
of
the
stomach
were
increased
in
comparison
to
Group
II
with
only
4­
NQO.
The
administration
of
SDDBS
by
itself
has
no
effect.
on
gastric
tumors
(
Group
III).
The
study
authors
concluded
.
that
the
increased
carcinogenicity
produced
by
SDDBS
was
due
to
the
better
uptake
of
4­
NQO
via
LAS'S
surfactive/
detersive
effects
on
the
protective
mucous
barrier
which
is
normally
found
in
the
glandular
stomach
and
other
gastric
compartments
of
the
rat.
The
effect
of
SDDBS
was
physical
rather
than
chemical
in
promoting
the
increased
tumorigenicity.

In
a
similar
study
by
the
same
investigators,
(
Takahasi,
MRID
43498419)
Motoyama
male
rats
were
divided
into
three
groups
and
gavaged
with
the
following
regimen;
Group
I
(
37
rats):
1
mg
4­
NQO
+
80
mg
SDDBS
+
20
mg
ethanol
in
a
1
ml
gavage
for
18
weeks.
Group
II
(
13
rats):
4­
NQO
and
ethanol
for
18
weeks.
Group
III
(
13
rats):
SDDBS
+
ethanol
for
18
weeks.

Again,
the
experiment
lasted
560
days
and
all
rats,
dying
on
study
or
terminally
sacrificed,
were
necropsied
and
examined
histologically
for
gastrointestinal
tumors.
Survival:
Mortality
was
59%
in
Group
I,
31%
in
Group
II
and
23%
in
Group
III.
Tumors:
Group
III
­
no
gastric
tumors
­
Group
II
­
9
benign
papillomas
of
forestomach
Group
1
­
8
benign
papillomas
of
forestomach,
2
malignant
papillomas
of
forestomach,
1
hemangiosarcoma
of
forestomach.
In
glandular
stomach,
2
adenocarcinomas,
1
hemangiosarcoma,
1
hemangioma,
5
squamous
cell
carcinomas
and
2
rats
exhibited
atrophic
gastritis.
The
increased
toxicity
in
Group
I
produced
increased
mortality
and
increased
numbers
of
malignant
tumors.
The
role
of
SDDBS
in
the
tumorigenesis
of
4 
NQO
was
to
promote
increased
absorption
o
4 
NQO
through
the
forestomach
and
glandular
stomach.

Core
Classification:
ACCEPTABLE
Carcinogenicity
Study
­
rat
MRID
No.
43498416
Randomized
groups
of
50/
sex/
group
weanling
Charles
River
CD
rats
were
fed
diets
for
24
months
containing
0,
0.02,
0.1
and
0.5%
LAS
(
200,
1000,
and
5000
ppm,
estimated
to
be
10,
50,
and
250
mg/
kg/
day).
Animals
were
housed
individually
and
observed
daily.
Body
­
weight
and
food
consumption
was­
measured
weekly
for
12
weeks
then­
monthly.
Interim
sacrifices
were
performed
on
5/
sex/
group
at
B
and
15
months.
Hematology
was
performed
(
RBCs,
differential,
WBC,
hematocrit).
Tail
blood
was
collected
from
5/
sex/
group
for
hematology
at
4,
11,
15,
and
21
months.
All
animals
killed
at
interim
sacrifice,
died
on
study,
or
terminally
sacrificed
were
necropsied
­
and­
representative
tissues
were
fixed
in
10%
Bouin
and
processed
for
H
&
E.
The
following
tissues
were
examined:
liver,
kidney,
thyroid,
trachea,
esophagus,
lungs,
heart,
spleen,
pancreas,
adrenal,
stomach,
small­
intestine,
urinary
bladder,
gonads,
mesenteric
lymph
nodes,
17
of
42
and
gross
lesions.
Liver
and
kidneys­
were
weighed
and
relative
organ
weights
calculated.
The
carcinogenic
aspects
of
the
study
are
considered
negative
at
5000
ppm
(
HDT),
which
is
less
than
the
MTD
since
no
toxicity
was
observed.
However,
it
should
be
considered
that
the
HDT
is
about
25%
of
the
LD50
dose
for
SDDBS.

According
to
the
report,
overall
survival
exceeded
56%
with
the
highest
rate
(
68%)
occurring
in
animals
on
0.5%
test
diet
as
compared
with
53%
in
controls.
There
were
no
treatment 
related
findings
in
hematology,
histopathology
or
tumor
results.
Chronic
interstitial
nephritis
and
adrenal
telangiectasis
were
the
most
commonly
observed
degenerative
conditions.
The
majority
of
tumors
were
subcutaneous
fibroadenomas.
No
data
were
presented
to
substantiate
these
statements.

870.4200b
Carcinogenicity
(
feeding)
­
Mouse
This
study
is
not
available
in
the
toxicology
database
of
this
chemical.

4.7
Mutagenicity
Adequacy
of
data
base
for
Mutagenicity:
The
data
base
for
Mutagenicity
is
considered
adequate
based.

Gene
Mutation
Guideline
870.5100
study
type:
Gene
Mutation
­
bacterial
MRID
No.
43498429
Classification:
Literature,
acceptable
Negative
at
cytotoxic
levels
or
limit
concentrations
(
both
with
and
without
S­
9
metabolic
activation)
when
tested
with
Salmonella
typhimurium
­
TA
98
and
TA
100
strains.

Cytogenetics
Guideline
#
870.5385
study
type:
Structural
Chromosomal
Aberrations
MRID
No.
43498428
Classification:
Literature,
acceptable
LAS
were
administered
to
rats
in
the
diet
for
90­
days
at
doses
of
0,
280,
or
565
mg/
kg/
d.
All
test
preparations
were
negative
for
increased
chromosomal
damage
over
controls.

Other
Genotoxicity
Guideline
#
870.5300
study
type:
In
Vitro
cell
transformation
MRID
No.
43498429
Classification,:
Literature,
acceptable
LAS
tested
negative
in
Syrian
Hamster
Ovary
(
SHE)
cells
at
up
to
50
micrograms/
plate.

4.8
Neurotoxicity
Adequacy
of
data
base
for
Neurotoxicity:
These
studies
are
not
available
or
required
at
this
time.
However,
there's
no
evidence
in
the
literature
to
indicate
any
neurotoxic
effects
of
LAS
in
humans
or
laboratory
animal.
18
of
42
4.9
Metabolism
Adequacy
of
data
base
for
metabolism:
The
data
base
for
metabolism
is
considered
to
be
complete.
No
additional
studies
are
required
at
this
time.

Absorption
and
distribution
in
major
organs
and
blood
were
studied.
Urine
was
collected
24
hours
after
topical
application
of
the
test
substance.
In
the
guinea
pig,
the
amount
of
35
S
excreted
in
the
urine
was
about
0.1%
of
the
total
administered
dose.
Organ
distribution
in
the
rat
was
about
5
times
greater
than
in
the
guinea
pig
and
"
relatively
large
amounts"
of
35
S
were
noted
in
the
liver
and
kidneys.

870.7485
Metabolism
 
Rat
In
a
rat
metabolism
study
(
MRID
43498431),
groups
of
Charles­
River
CD
male­
rats,
150­
200g
BW,
were
used
in
the
study.
LAS­
S35
was
given
orally
to
fasted
rats
at
doses
of
0.6,
1.2,
8,
and
40
mg.
Urine
and
feces
were
collected
and
analyzed
for
radioactivity.
Tissues
were
taken
for
immunoassay
at
the
end
of
the
study.
For
metabolism
studies,
urine,
bile,
or
feces
were
pooled.

The
rate
and
distribution
of
the
excreted
dose
was
independent
of
concentration.
Similar
levels
of
radioactivity
were
found
in
urine
and
feces
and
within
3
days,
85.2%
­
96.6%
of
the
label
was
recovered
in
the
high
dose
rats,
no
detectable
radioactivity
was
found
in
the
carcasses
after
3
days.
The
limit
of
sensitivity
was
0.1%
of
the
dose.
Urinary
S35
was
not
in
inorganic
form
and
no
intact
LAS­
S35
was
detected.
Following
methylation,
one
urinary
metabolite
was
identified
as
4­
(
4'­
methylsulfophenyl)
pentanoate.
LAS­
S35
in
the
feces
remained
un­
metabolized.

The
absorption
in
rats
with
a
ligated
bile
duct
by
a
single
gavage
dose
of
1.2
mg
LAS­
S35
demonstrated
that
gastrointestinal
absorption
did
not
require
enterohepatic
circulation,
since
most
of
the
oral
dose
was
found
in
the
urine
(
74%)
and
only
9%
was
found
in
feces.
Recovery
was
83%.

Enterohepatic
recirculation
was
found
to
be
not
an
important
factor
in
LAS 
S35
excretion
by
studies
in
rats
with
cannulated
bile
ducts
given
1.2
mg/
kg
of
LAS­
S35
orally.
The
percent
of
radioactivity
in
bile
was
similar
to
that
in
feces
and
most
label
was
in
the
urine.

Core
Classification:
ACCEPTABLE
Metabolism
 
Monkey
In
a
Monkey
metabolism
study
(
MRID
No
43498410),
two
groups
of
2
male
and
2
female
Rhesus
monkeys,
5
kg
BW,
were
used
for
the
oral
and
subcutaneous
metabolism
studies
(
one
group
for
each
route
of
exposure).
For
the
oral
studies,
each
animal,
following
2­
3
weeks
between
dose
levels,
received
single
oral
doses
of
C14(
SDDBS;
25
microcuries.)
at
levels
of
30,
150,
and
300
mg/
kg.
Blood,
urine,
faces
and
cage
washing
samples
were
taken
for
mass
balance,
metabolite
identification
and
plasma
kinetics.
Following
2­
3
weeks
after
the
last
single
oral
dose,
each
monkey
received
7
consecutive
daily
oral
doses
of
30
mg/
kg/
day
of
C14
ALS.
Animals
were
sacrificed
after
the
last
dose
and
tissue
samples
taken
for
direct
combustion.
19
of
42
For
the
subcutaneous
studies,
each­
animal,
following
2­
3
weeks
between
dose
levels,
received
single
subcutaneous
doses
of
C14
LAS
(
SDDBS;
25
microcuries)
at
levels
of
0.1,
0.5
and
1.0
mg/
kg.
Blood,
urine,
feces
and
cage
washing
samples
were
taken
for
mass
balance,
metabolite
identification
and
plasma
kinetics.
Following
2­
3
weeks
after
the
last,
single
subcutaneous
dose,
each
monkey
received
7
consecutive
daily
subcutaneous
doses
of
1.0
mg/
kg/
day
of
C14
LAS.
Animals
were
sacrificed
after
the
last
dose
and
tissue.
samples
taken
for
direct
combustion.

After
single
30
mg/
kg
doses
the
radioactivity
was
rapidly
excreted,
mostly
during
the
first
24
hours.
Feces
and
urine
contained
23.1%
and
71.2%,
respectively,
in
the
first
5
days
after
oral
dosing.
After
subcutaneous
injection,
10.9%
and
64.1%
were
found
in
the
urine
and
feces,
respectively,
after
the
same
period.

Plasma
concentrations
were
comparable
after
single
oral
doses
of
30,
150,
and
300
mg/
kg
at
4
hours
and
averaged
34,
41,
and
36
u/
ml,
respectively.
Peak
plasma
concentrations
increased
proportional
to
dose
after
single
subcutaneous
injections
of
0.1,
0.5,
and
1
mg/
kg
and
were
0.16,
0.72,
and
1.13
u/
ml,
respectively.

During
the
7
day
dosing
period,
either
by
oral
or
subcutaneous
injection,
there
was
no
accumulation
of
radioactivity
in
plasma,
since
peak
concentrations
and
half­
lives
were
similar
after
the
first
and
seventh
dose.
Animals
sacrificed
after
the
seventh
dose
showed
no
localization
in
any
of
the
examined
tissues.
In
urine
samples
analyzed
for
metabolites,
there
was
no
unchanged
SDDBS
and
the
5
metabolites
detected
were
polar,
but
were
not
sulphate
or
glucuronide
conjugates.

Core
Classification:
ACCEPTABLE
870.7600
Dermal
Absorption
­
Rat
No
dermal
absorption
studies
are
available
in
the
toxicology
database.

Studies
(
Howes,
1975)
with
isolated
human
skin
preparations
as
well
as
in
vivo
investigations
of
percutaneous
administration
of
LAS
to
rats
have
demonstrated
that
penetration
through
skin
and
subsequent
systemic
absorption
of
this
surfactant
does
not
occur
to
any
significant
extent
at
24
to
48
hours.
14
C­
LAS
was
applied
on
the
clipped
dorsal
skin
of
the
rats,
which
was
washed
after
15
min.
No
radioactivity
was
detected
in
urine
or
feces.

4.10
Special/
Other
Studies:
N/
A
5.0
TOXICITY
ENDPOINT
SELECTION
5.1
See
Section
9.2
for
Endpoint
Selection
Table.

5.2
Dermal
Absorption:
Quantification
of
dermal
risk
is
not
required
since:
1)
the
alkylbenzene
sulfonates
are
surfactants
that
are
dermal
irritants
at
concentrations
generally
greater
than
20%
solution.
Thus,
dermal
20
of
42
exposure
would
be
self­
limiting
to
preclude
dermal
irritation.
Additionally,
the
requirement
of
the
dermal
toxicity
studies
with
the
end­
use
product
will
determine
and
be
used
for
the
personal
protective
clothing
necessary
to
protect
against
irritation
during
product
use;
2)
no
systemic
toxicity
was
seen
following
repeated
dermal
applications
to
rabbits
at
200
mg/
kg/
day
(
with
an
end
use
product),
and
3)
no
developmental
toxicity
concerns
were
seen
following
repeated
dermal
applications
to
pregnant
mice,
rats
or
rabbits
(
developmental
effects
were
seen
either
in
the
presence
of
maternal
toxicity
or
at
doses
higher
than
those
that
caused
maternal
toxicity).

5.3
Classification
of
Carcinogenic
Potential:
There
was
no
Cancer
Assessment
Review
Committee
(
CARC)
for
LAS;
however,
from
the
available
data
it
doesn't
appear
that
LAS
has
carcinogenic
potential.
The
WHO
(
1996)
acknowledged
that
the
available
studies
are
inadequate
to
assess
the
carcinogenic
potential
of
LAS,
but
they
also
concluded
that
the
data
show
no
evidence
of
carcinogenicity.

6.0
FQPA
CONSIDERATIONS
6.1
Special
Sensitivity
to
Infants
and
Children
Based
on
the
available
hazard
data,
it
doesn't
appear
that
LAS
exposure
in
laboratory
animal
studies
results
in
any
special
sensitivity
to
the
young.
Therefore,
the
FQPA
factor
may
be
reduced
to
1X.

Several
reproduction
and
many
developmental
studies
have
been
performed
with
LAS
in
a
number
of
animal
species.
In
the
developmental
studies,
whenever
toxicity
was
observed
in
adults,
it
was
generally
for
mild
effects
(
slight
body
weight
changes,
intestinal
disturbances)
except
for
severe
dermal
irritation
effects
in
dermal
developmental
studies.
Any
developmental
toxicity
observed
in
these
same
studies
included
minor
increases
in
visceral/
skeletal
anomalies
and
some
fetal
losses;
but
only
at
maternally
toxic
doses.

In
one
reproduction
study
(
Buehler
et
al.,
1971),
there
were
slight
changes
in
hematology
and
histopathology
(
both
within
historical
control
ranges)
and
slight
decreases
in
body
weight
in
the
offspring
at
the
highest
dose
of
250
mg/
kg/
d
(
at
which
there
were
no
effects
on
the
parental
generation).
There
were
no
effects
in
either
the
parental
or
offspring
in
the
other
two
reproductive
toxicity
studies
(
see
Toxicity
Profile
Table)
 
high
doses
of
70
or
170
mg/
kg/
d.

There's
no
evidence
in
the
literature
to
indicate
any
neurotoxic
effects
of
LAS
in
humans
or
laboratory
animal.

There
is
no
need
for
a
special
FQPA
factor
because
the
mid­
dose
level
of
50
mg/
kg/
d
(
NOAEL
for
offspring
effects)
in
the
Buehler
study
is
the
basis
for
the
chronic
RfD
of
50
mg/
kg/
d.
Thus,
the
chronic
hazard
value
is
based
on
slight
pup
effects
and
is
protective
of
laboratory
animals
of
all
ages
in
this
hazard
assessment.
21
of
42
6.2
Recommendation
for
a
Developmental
Neurotoxicity
Study
A
DNT
is
not
required
because
there
is
no
evidence
of
either
neurotoxicity
or
susceptibility
to
the
young
following
LAS
exposure
to
laboratory
animals.

7.0
OTHER
ISSUES:
N/
A
8.0
REFERENCES
in
MRID
order
MRID
No.
Guideline
No./
Study
Type
Source
Multiple
studies
870.1100
Acute
oral
toxicity
Tox
Oneliner
94032006
870.1200
Acute
dermal
toxicity
Tox
Oneliner
003442*
870.1300
Acute
inhalation
toxicity
Tox
Oneliner
0033443*
870.2400
Acute
eye
irritation
Tox
Oneliner
003444*
870.2500
Acute
dermal
irritation
Tox
Oneliner
N/
A
870.2600
Skin
sensitization
Open
Literature
N/
A
870­
3100
Subchronic
Oral
Toxicity
 
Rat
Ikawa
et
al.
1978.
HERA­
2004)
N/
A
870­
3100
Subchronic
Oral
Toxicity
 
Rat
Ito,
et
al.
(
1978)
J.
Med.
Soc.
Toho
Univ.
25:
850­
875.
43498413
Subchronic
Oral
Toxicity
 
Monkey
HERA­
2004
N/
A
21/
28­
Day
Dermal
Toxicity
 
Guinea
Pig
Mathur
et
al.
(
1992).
J
Toxicol
Cutan
Ocular
Toxicol,
11(
1):
3­
13.
(
WHO
169).
43498403
Subchronic
Inhalation
Toxicity
 
Monkey
HERA­
2004
43498426
870.3700a
Prenatal
Developmental
Toxicity
Study
 
Rat,
Mouse,
Rabbit,
Palmer
et
al.
Part
I,
HERA­
204
43511403
Dermal
Developmental
Toxicity
 
Rat,
Rabbit,
Mouse
Palmer
et
al.
Part
III,
HERA­
2004
43498424
&
43498425
Mouse­
Developmental
43498416
870.3800
Reproduction
and
Fertility
Effects
 
Rat
870.4100a
Chronic
Toxicity
 
Rat
Yoneyama
et
al.,
1976
(
see
tox
profile
table)
870.4100b
Chronic
Toxicity
 
Mouse
Yoneyama
et
al.,
1976
(
see
tox
profile
table)
43498420
&
43498419
870.4200a
Carcinogenicity
Study
 
rat
43498416
870.4200a
Carcinogenicity
Study
 
rat
22
of
42
MRID
No.
Guideline
No./
Study
Type
Source
43498429
870.5100
Gene
Mutation
­
bacterial
43498428
870.5385
Structural
Chromosomal
Aberrations
43498427
870.5300
In
Vitro
cell
transformation
MRID
No.
Guideline
No./
Study
Type
Source
43498431
870.7485
Metabolism
 
Rat
43498410
Metabolism
 
Monkey
Isolated
human
skin
preparations
Howes,
1975
(
see
tox
profile
table)
*
Tox
record
No.

Other
Sources:

World
Health
Organization
(
WHO).
1996.
Environmental
Health
Criteria
Document
for
Linear
Alkylbenzene
Sulfonates
and
Related
Compounds.
(
EHC
169,
available
at
http://
www.
inchem.
org/
documents/
ehc/
ehc/
ehc169.
htm
)

Human
and
Environmental
Risk
Assessment
(
HERA).
2004.
LAS
 
Linear
Alkylbenzene
Sulfonates
(
CAS
No.
68411­
30­
3).
24
of
42
9.0APPENDICES
Tables
for
Use
in
Risk
Assessment
25
of
42
9.1
Toxicity
Profile
Summary
Tables
9.1.1
Acute
Toxicity
Table
­
See
Section
4.1
9.1.2
Subchronic,
Chronic
and
Other
Toxicity
Tables:

Guideline
No./
Study
Type
MRID
No./
Reference
Information/
Study
Classification
Dosing
and
Animal
Information
Results
Subchronic
Toxicity
870.3100
Oral
Subchronic
(
rodent)
Bornmann
et
al
(
1963)
Study
of
a
Detergent
Based
on
Dodecylbenzene
Sulfonate.
Fette
Seifen
Anstrichm,
65
(
10):
818­
824.
(
EHC
169)

Open
Literature
0.01%
of
a
preparation
containing
51%
LAS
was
administered
in
the
drinking
water
for
100
weeks
Rats
(
60/
sex)

Purity:
Not
Reported
No
detrimental
effects
on
body
weight
and
no
pathological
effects,
including
tumors,
were
reported
870.3100
Oral
Subchronic
(
rodent)
Ikawa
et
al.,
(
1980)/
Ann.
Rep.
Tokyo
Metrop.
Res.
Lab.
Public
Health.
29(
2):
51­
54(
Z).
1978
(
in
Japanese,
see
WHO,
1996
and
HERA,
2004).

Open
Literature
LAS
was
administered
for
2,
4,
or
12
weeks
at
a
single
dose
of
1.5%
in
the
diet
(
750
mg/
kg/
d).

Male
rats
(
five/
group)

Purity
not
reported.
LAS
suppressed
body
weight
gain
and
the
relative
liver
weight
was
increased
after
two
weeks.
Serum
biochemical
alterations
included:
significant
increases
in
ALP,
GTP
(
at
2,
4,
12
weeks);
significant
decreases
in
cholesterol
and
protein
(
4
weeks);
decreases
in
liver
enzymes
G6Pase
and
G6PDH
and
increases
in
isocitrate
DH
(
all
at
2,
4,
12
weeks).
The
following
enzymes
associated
with
kidney
function
were
also
altered:
decreases
in
G6Pase,
5'
nucleotidase
(
at
2,
4,
12
weeks)
and
Na,
K­
ATPase
(
12
wks);
increase
in
LDH
(
12
wks)
and
IDH
(
2,4
wks).

870.3100
Oral
Subchronic
(
rodent)
Ito,
et
al.
(
1978)
Acute,
Subacute,
and
Chronic
Toxicity
of
Magnesium
LAS
(
LAS­
Mg).
J.
Med.
Soc.
Toho
Univ.
25:
850­
875.

Open
Literature
Administration
by
oral
gavage
at
doses
of
0,
155,
310,
or
620
mg/
kg/
day
(
LAS­
Mg)
and
125,
250,
and
500
mg/
kg/
day
(
LASNa
for
one
month
Sprague­
Dawley
Rats
(
12/
sex/
group)

Purity:
99.5%
LAS­
Na:
Body
weight
increase
was
suppressed;
feedefficacy
was
decreased,
and
liver
weight
increased
at
500
mg/
kg/
day.
NOAEL:
125
mg/
kg
bw/
d.

870.3100
Oral
Subchronic
(
rodent)
MRID
No.
43498412
Kay
et
al.
(
1965)
Subacute
Oral
Toxicity
of
a
Biodegradable,
Linear
Alkylbenzene
Sulfonate.
Toxicol
Appl.
Pharmacol.
7:
812­
818
(
HERA)

Acceptable
Guideline
SDDBS
administered
in
the
diet
at
dietary
levels
of
0,
200,
1000,
and
5000
ppm
for
90
days
Weanling
Sprague­
Dawley
Rat
(
10/
sex/
dose)

Purity:
87.9%
a.
i.
NOEL:
5000
ppm
(
HDT)

Two
low
dose
males
died
early
in
the
study
from
respiratory
illness
There
was
no
compound­
related
effects
in
body
weight,
food
consumption,
hematology,
urine
analysis,
organ
weight,
and
histopathology.

870.3100
Oral
Subchronic
(
rodent)
MRID
No.
43511401
Mathur
et
al.
(
1986)
Toxicological
Evaluation
of
a
Synthetic
Detergent
LAS
was
administered
as
a
commercial
synthetic
detergent
solution
at
doses
of
0,
50,
100,
or
250
mg/
kg/
day
in
the
feed
for
10
weeks
NOEL:
<
50
mg/
kg/
d
LOEL:
50
mg/
kg/
d
based
on
alterations
of
several
enzymes
indicative
of
liver
and
kidney
damage
26
of
42
Guideline
No./
Study
Type
MRID
No./
Reference
Information/
Study
Classification
Dosing
and
Animal
Information
Results
after
Repeated
Oral
Ingestion
in
Rats.
Industrial
Toxicology
Research
Centre,
Mahatma
Ganghi
Marg,
Lucknow
Study
No.
DDBSA
JV­
RP­
013.
Acceptable
F
Albino
Rat
(
9/
group)

Purity:
Not
Reported
870.3100
Oral
Subchronic
(
rodent)
MRID
No.
43498402
Oser
et
al.
(
1965)
Toxicologic
Studies
with
Branched
and
Linear
Alkyl
Benzene
Sulfonates
in
the
Rat.
Toxicol.
Appl.
Pharmacol.
7:
819­
825.
(
HERA)

Acceptable
Guideline
LAS
and
ABS
were
administered
at
dietary
levels
of
0,
50,
or
250
mg/
kg/
day,
adjusted
for
bw
and
fc,
for
90
days
FDRL
Strain
(
Wistarderived
Rat
(
15/
sex/
dose)

Purity:
Not
Reported
NOEL:
50
mg/
kg/
d
LEL:
250
mg/
kg/
d
for
increased
absolute
and
relative
liver
weight
in
both
sexes
(
21%)
and
increased
relative
cecal
weight
(
21%)
in
males
870.3100
Oral
Subchronic
(
rodent)
Watari
et
al.
(
1977)
Ultrastructural
Observations
of
the
Protective
Effect
of
Glycyrrhizin
for
Mouse
Liver
Injury
Caused
by
Oral
Administration
of
Detergent
Ingredients
(
LAS),
J.
Clin.
Electron.
Microscopy
(
Nihon
Rinsho
Denshikenbikyo
Kaishi)
10
(
1­
2):
121­
139.

Open
Literature
Benzenesulfonic
acid,
C10­
13­
alkyl
derivatives,
sodium
salt
was
administered
in
the
drinking
water
for
6
months
at
0
and
100
ppm
with
2
months
recovery
(
M:
0
and
17
mg/
kg
bw,
F:
0
and
20
mg/
kg
bw)

M/
F
ddy
Mouse
Purity:
Not
Reported
Liver
effects
were
observed
at
the
only
dose
tested
(
17­
20
mg/
kg/
d),
but
they
disappeared
following
the
2­
month
recovery
period.

870.3100
Oral
Subchronic
(
rodent)
Yoneyama
&
Hiraga
(
1977)
Effect
of
Linear
Alkylbenzene
Sulfonate
on
Serum
Lipid
in
Rats,
J
Ann
Rep
Tokyo
Metrop
Res
Lab,
Public
Health
28(
2):
109­
111.
(
HERA)

Open
Literature
LAS
was
administered
in
the
diet
at
concentrations
of
180,
360,
or
540
mg/
kg
bw/
d
for
two
and
four
weeks
M
Wistar
Rat
(
5/
group)

Purity:
60%
a.
i.
Body
weight
gain
was
suppressed
in
the
group
receiving
540
mg/
kg
bw/
d
at
four
weeks,
and
the
relative
liver
weight
was
increased
at
two
weeks
and
thereafter
in
the
groups
receiving
360
mg/
kg
bw/
d
and
540
mg/
kg
bw/
d.
The
levels
of
triglyceride
and
total
lipids
in
the
serum
had
decreased
markedly
at
two
weeks
in
all
the
experimental
groups,
and
the
levels
of
phospholipids
and
cholesterol
in
the
serum
had
decreased
significantly
at
two
weeks
in
the
groups
given
360
and
540
mg/
kg
bw/
d.
These
changes
were
less
apparent
at
four
weeks,
but
triglyceride,
phospholipid,
and
cholesterol
levels
in
serum
were
significantly
decreased
in
the
group
given
540
mg/
kg
bw.
Significant
increases
in
triglyceride
levels
were
seen
in
the
liver
after
two
weeks
in
the
groups
receiving
180
and
540
mg/
kg
bw/
d,
and
in
cholesterol
levels
in
the
group
given
180
mg/
kg
bw.

870.3100
Oral
Subchronic
(
rodent)
Yoneyama
et
al.
(
1978)
Effects
of
LAS
on
Incorporation
of
Acetate­
1­
14C
in
Liver
Lipids
in
Rats.
J
Ann
Rep
Tokyo
Metrop
Res
Lab
Public
Health,
29
(
2):
55­
57.
LAS
was
administered
at
a
concentration
of
200
mg/
kg
bw/
d
in
the
diet
or
in
drinking
water
(
560
mg/
kg
bw/
d)
for
two
weeks
to
determine
the
effect
on
the
synthesis
of
lipids
in
the
liver
Uptake
of
acetate­
1­
14C
by
lipids
in
the
liver
was
increased
in
both
groups;
uptake
of
phospholipids
and
triglycerides
tended
to
increase,
and
that
of
phospholipids
increased
significantly
in
rats
given
LAS
in
the
diet.
27
of
42
Guideline
No./
Study
Type
MRID
No./
Reference
Information/
Study
Classification
Dosing
and
Animal
Information
Results
Open
Literature
M
Wistar
Rat
(
5/
group)

Purity:
Not
Reported
870.3100
Oral
Subchronic
(
rodent)
MRID
No.
43498413
Heywood
et
al.
(
1978)
Toxicology
Studies
of
Linear
Alkyl
Sulfonate
(
LAS)
in
Rhesus
Monkeys
I.
Simultaneous
Oral
and
Subcutaneous
Administration
for
28
Days.
Toxicol.
Appl.
Pharmacol.
11:
245­
250.
(
HERA)

Acceptable
Guideline
LAS
was
given
to
four
groups
of
three
males
and
three
females
at
doses
of
30,
150,
300
mg/
kg
bw/
day
per
gavage
(
po)
and
simultaneously
with
0.1,
0.5,
or
1.0
mg/
kg
bw/
day
subcutaneously
(
sc).
Control
groups
were
used.

Rhesus
Monkey
(
3/
sex/
dose),
18­
36
months
old
Purity:
Not
Reported
At
300
(
po)
and
1.0
(
sc)
mg/
kg
bw/
day,
the
monkeys
vomited
frequently
and
usually
within
3
hours
of
administration.
An
increased
frequency
of
loose
or
liquid
faeces
was
recorded
for
animals
receiving
150
(
po)
and
0.5
(
sc)
mg/
kg
bw/
day.
These
effects
are
probably
related
to
the
inherent
irritative
effects
of
LAS
rather
than
to
its
systemic
toxicity.
Fibrosis
of
the
injection
sites
was
found
among
the
entire
test
group,
the
incidence
and
severity
being
dose
related.
Ophthalmoscopy,
laboratory
examination
of
blood
and
urine,
organ
weight
analysis
and
histopathological
investigation
did
not
detect
any
further
treatment­
related
responses.

The
LOAEL
is
150
mg/
kg
bw/
day
(
po)
+
0.5
mg/
kg
bw/
day
(
sc)
based
on
an
increase
in
liquid
feces
and
the
NOAEL
is
30
mg/
kg/
d
870.3200
21­
Day
Dermal
Mathur
et
al.
(
1992)
Effect
of
Dermal
Exposure
to
LAS
Detergent
and
HCH
Pesticide
in
Guinea
Pigs:
Biochemical
and
Histopathologic
Changes
in
Liver
and
Kidney.
J
Toxicol
Cutan
Ocular
Toxicol,
11(
1):
3­
13.
(
WHO
1996)

Open
Literature
A
solution
of
LAS
in
distilled
water
equivalent
to
60
mg/
kg
bw
was
applied
to
a
4­
cm2
area
of
clipped
dorsal
skin
daily
for
30
days
12
Guinea
Pigs
Purity:
Not
Reported
The
activities
of
B­
glucuronidase,
gamma­
glutamyl
transpeptidase,
5­
nucleotidase,
and
sorbitol
dehydrogenase
were
increased
in
liver
and
kidney.
Lipid
peroxidation
was
increased
in
the
kidney
but
not
in
liver,
and
the
glutathione
content
was
unchanged
in
both
organs.
Extensive
fatty
changes
were
found
in
hepatic
lobules,
with
dilation
of
sinusoids;
tubular
lesions
were
found
in
the
kidney,
predominantly
in
the
proximal
and
distal
portions.

870.3200
21­
Day
Dermal
Tox
Record
No.
003441
Subchronic
(
28­
day)
Percutaneous
Toxicity
(
Rabbit)
of
Compound:
B0002.01,
(
Bio/
dynamics
Inc.,
Project
No.
4717­
77,
March
17,
1978,
submitted
by
Procter
and
Gambel
Company,
May
10,
1978).

Unacceptable
Core­
Minimum
Data
SDDBS
(
end
use
product
Comet
Cleanser)
was
applied
to
the
skin
of
rabbits
for
28
days
at
200
mg/
kg/
d.
The
hair
of
each
rabbit
was
clipped
from
its
trunk,
so
as
to
expose
approximately
25%
of
the
total
body
surface
area
and
the
skin
was
abraded
daily
just
prior
to
treatment.

20
M/
F
Albino
New
Zealand
White
Rabbits
(
5/
sex/
group)

Purity:
10%
NOEL:
>
200
mg/
kg/
d
870.3465
90­
Day
Inhalation
MRID
No.
43498403
Coate
et
al.
(
1978)
Respiratory
Toxicity
of
Enzyme
Detergent
Dust.
Toxicol.
Appl.
SDDBS
was
administered
a
SDDBS
mixture
at
levels
of
0,
100(
detergent),
and
[
.001,
.01,
0.1
and
1
(
enzyme)]
together
with
[+
0,
1,
10,
and
100
NOEL:
1
mg/
m3
detergent
dust
combined
with
up
to
0.1
mg/
m3
enzyme
dust.

The
detergent
dust
alone
at
100
mg/
m3
caused
gross
signs
of
respiratory
distress,
pulmonary
histopathological
effects,
and
pulmonary
function
28
of
42
Guideline
No./
Study
Type
MRID
No./
Reference
Information/
Study
Classification
Dosing
and
Animal
Information
Results
Pharmacol.,
45:
477­
496.

Acceptable
Guideline
(
detergent)]
mg/
m3
for
6
hours
daily,
5
days
a
week,
for
6
months
12
groups
of
5
M/
4
F
Cynomolgus
Monkeys
Purity:
13%
impairment
indicative
of
constricted
bronchioles.
Exposure
to
10
or
100
mg/
m3
together
with
0.01
and
0.1
mg/
m3
enzyme
dust
produced
the
same
effects
along
with
weight
loss
and
decreased
weight
gain.

Developmental
Toxicity
870.3700a
Developmental
Toxicity
(
rodent)
Daly
et
al.
(
1980)
A
Teratology
Study
of
Topically
Applied
LAS
in
Rats,
Fd.
Cosmet.
Toxicol.
18:
55­
58.
(
HERA)

Open
Literature
LAS
was
applied
to
the
skin
on
days
0
through
21
of
gestation
at
doses
of
20,
100,
and
400
mg/
kg
bw/
d
Rat
Purity:
Not
Reported
NOAEL
(
maternal):
20
mg/
kg
bw/
d
NOAEL
(
fetuses):
400
mg/
kg
bw/
d
Maternal
toxicity:
the
dams
treated
with
400
mg/
kg
bw/
day
and
100
mg/
kg
bw/
day
showed
inhibition
of
body
weight
gain
and
llocal
skin
effects
that
compromised
the
integrity
of
the
skin
and
caused
overt
toxicity,
like
inhibition
of
the
body
weight
gain.
Teratogenicity:
there
were
no
findings
indicative
of
effects
of
LAS
on
the
foetal
parameters
evaluated.
There
were
no
indications
of
teratogenic
or
embryotoxic
effects.

870.3700a
Developmental
Toxicity
(
rodent)
Endo
et
al.
(
1980)
Studies
of
the
Chronic
Toxicity
and
Teratogenicity
of
Synthetic
Surfactants,
Ann.
Rep.
Tokyo
Metrop.
Res.
Inst.
Environ.
Prot.
(
Tokyo
Kogai
Kenkyujo
Nempo),
236­
246.
(
HERA)

Open
Literature
LAS
was
administered
in
the
drinking
water
at
0.1%,
corresponding
to
383
mg/
kg
bw/
d
for
rats
and
up
to
3030
mg/
kg
bw/
d
for
rabits
from
day
6
to
15
(
rats)
and
day
6
to
18
(
rabbits)
of
pregnancy.

F
Rat
and
Rabbit
Purity:
Not
Reported
NOAEL
(
maternal):
383
mg/
kg
bw/
d
(
rat)
LOAEL
(
maternal):
3030
mg/
kg
bw/
d
(
rabbit)
NOAEL
(
fetuses):
383
mg/
kg
bw/
d
(
rat)
LOAEL
(
fetuses):
3030
mg/
kg
bw/
d
(
rabbit)

The
effect
on
the
dams
was
a
slight
inhibition
of
body
weight
gain
in
the
rabbits.
The
litter
parameters
of
both
species
did
not
show
any
significant
differences
from
those
of
the
controls.
Delayed
ossification
was
observed
in
rabbits,
but
there
was
no
increase
in
malformations
in
either
the
rabbits
or
the
rats.

870.3700a
Developmental
Toxicity
(
rodent)
Imahori
et
al.
(
1976)
Effects
of
LAS
Applied
Dermally
to
Pregnant
Mice
on
the
Pregnant
Mice
and
their
Fetuses,
J.
Jpn.
J.
Public
Health
(
Nihon
Koshueisei
Zasshi)
23(
2):
68­
72.
(
HERA)

Open
Literature
LAS
was
applied
daily
at
dermal
doses
of
15,
150,
and
1500
mg/
kg
bw/
d
on
days
6
through
day
15
of
pregnancy
F
Mouse
Purity:
Not
Reported
NOAEL
(
maternal):
150
mg/
kg
bw/
d
NOAEL
(
fetuses):
1500
mg/
kg
bw/
d
The
1500
mg/
kg
bw/
day
group
showed
a
clear
decrease
in
the
pregnancy
rate
(
67.9%)
when
compared
with
a
rate
of
96.3%
in
the
controls.
However,
there
were
no
decreases
in
the
litter
size,
and
no
changes
in
the
litter
parameters
with
the
exception
of
a
slight
decrease
in
foetal
body
weight.
There
were
no
significant
increases
in
the
incidence
of
malformations
in
the
foetuses.

870.3700a
Developmental
Toxicity
(
rodent)
MRID
No.
43498423
Masuda
et
al.
(
1974)
Effects
of
LAS
Applied
Dermally
to
Pregnant
Mice
on
the
Development
of
their
Fetuses.
15:
349­
355.

Acceptable
Guideline
LAS
was
applied
dermally
at
a
level
of
0.5
ml.
The
ICR­
JCL
strain
received
doses
of
0,
0.85,
1.7,
2.55,
and
3.4%
solutions
daily
from
days
1
to
13
of
gestation
and
the
ddY
strain
received
doses
of
0,
0.017,
0.17,
and
1.7%
solutions
daily
from
days
2
to
14
of
gestation.

Mouse
(
ICR­
JCL
strain
and
ddY
strain)

Purity:
Not
Reported
NOEL
(
maternal
and
developmental
toxicity
­
ddY):
1.7%
(
HDT)
NOEL
(
maternal
toxicity
­
ICR­
JCL):
2.55%
NOEL
(
developmental
toxicity
­
ICR­
JCL):
1.7%

At
3.4%
LAS,
maternal
body
weight
and
the
absolute
weight
of
liver,
kidney,
spleen
were
significantly
increased
over
control..
Pregnancy
rates
were
significantly
less
(
33.35)
compared
to
controls
(
69%).
The
number
of
implantations,
live
fetuses,
sex
ratio,
dead
or
resorbed
fetuses,
placenta
weight
and
external
malformations
were
comparable
with
control.
Fetal
body
weights
of
2.55%
and
3.4%
LAS­
treated
groups
were
significantly
less
than
controls.
29
of
42
Guideline
No./
Study
Type
MRID
No./
Reference
Information/
Study
Classification
Dosing
and
Animal
Information
Results
870.3700a
Developmental
Toxicity
(
rodent)
MRID
43498424
and
43498425
Nomura,
T
et
al.
(
1980)
The
Synthetic
Surfactants
AS
and
LAS
Interrupt
Pregnancy
in
Mice.
Life
Sciences,
26:
49­
54.
(
HERA)

Nomura,
T.
et
al.
(
1987)
Killing
of
Preimplantation
Mouse
Embryos
by
AS
and
LAS.
Mutation
Research
190:
25­
29.
(
HERA)

Acceptable
Guideline
LAS
(
0.1
ml
)
was
applied
at
a
concentration
of
20%
to
the
dorsal
skin
of
pregnant
mice
during
the
pre­
implantation
period
twice
a
day
from
day
0
to
day
3
of
pregnancy
Female
ICR/
Jcl
Mouse,

9­
10
weeks
old
Purity:
20%
Development
was
retarded
and
cleavage
of
eggs
was
interrupted.
Significantly
higher
numbers
of
embryos
were
found
to
be
deformed
in
the
LAS
group
in
comparison
to
controls,
and
most
of
these
embryos
were
in
the
morula
stage,
whereas
they
were
mostly
in
the
last
blastocyst
stage
in
controls.

Some
dead,
deformed,
and
growth­
retarded
embryos
were
observed
in
the
treated
group.
Although
the
authors
stated
that
these
effects
were
not
due
to
maternal
toxicity
since
no
maternal
organs
were
affected,
this
statement
is
probably
not
correct
in
view
of
the
high
concentration
of
LAS
and
its
irritation
effects.
A
secondary
effect
due
to
maternal
toxicity
appears
much
more
likely.

870.3700a
Developmental
Toxicity
(
rodent)
MRID
43498426
Palmer
et
al.
(
1975)
Assessment
of
the
Teratogenic
Potential
of
Surfactants,
(
Part
I),
Toxicology
3:
91­
106.

Acceptable
Guideline
LAS
was
administered
by
gavage
on
days
6­
15
of
pregnancy
in
rats
and
mice
and
days
6­
18
of
pregnancy
in
rabbits
at
doses
of
0.2,
2,
300,
and
600
mg/
kg
bw/
d
20
CD
Rats,
20
CD­
1
Mice,
and
13
New
Zealand
White
Rabbits
Purity:
17%
NOAEL
(
rat
­
maternal):
300
mg/
kg
bw/
d
NOAEL
(
mouse
­
maternal):
2.0
mg/
kg
bw/
d
(
However,
there
is
a
large
difference
between
this
dose
and
the
next
highest
dose
of
300
mg/
kg
bw/
d,
this
study
does
not
allow
determination
of
a
reliable
maternal
NOAEL
for
mice)

NOAEL
(
rabbit
­
maternal):
2.0
mg/
kg
b/
d
(
However,
the
study
does
not
allow
determination
of
reliable
NOAELs,
given
the
large
difference
between
the
maternal
no­
effects
doses
of
2
mg/
kg
bw/
d
and
the
maternal
LOAEL
dose
(
300
mg/
kg
bw/
d)
that
is
also
the
dose
for
which
effects
on
litters
could
not
be
determined
due
to
the
high
mortality
rate
in
parent
animals)

NOAEL
(
rat
­
developmental):
300
mg/
kg
bw/
d
NOAEL
(
mouse
­
developmental):
2.0
mg/
kg
bw/
d
NOAEL
(
rabbit
­
developmental):
2.0
mg/
kg
bw/
d
NOAEL
(
rat
­
fetal):
600
mg/
kg
bw/
d
NOAEL
(
mouse
­
fetal):
300
mg/
kg
bw/
d
(
Due
to
a
high
mortality
rate
of
parent
animals,
no
assessment
was
possible
at
600
mg/
kg
bw/
d)
NOAEL
(
rabbit
­
fetal):
could
not
be
determined
870.3700a
Developmental
Toxicity
(
rodent)
MRID
43511403
Palmer,
et
al.
(
1975)
Assessment
of
the
Teratogenic
Potential
of
Surfactants,
(
Part
III)
­
Dermal
Application
of
LAS
and
Soap.
Huntingdon
Research
Centre,
Huntingdon,
Great
Britain.
Study
No.
DDBSA
JV­
RP4­
029.
Toxicology
4:
171­
181.

Acceptable
Guideline
LAS
was
administered
percutaneously
to
shaved
skin
at
solutions
of
0.03%,
0.3%,
and
3%
during
pregnancy
on
days
2­
13
in
mice,
2­
15
in
rats,
and
1­
16
in
rabbits.
Dosages
employed
were
0.5
ml/
rat
or
mouse/
day
and
10
ml/
rabbit/
day
CD­
1
Mice
(
20/
group),
CD
Rats
(
20/
group),
N2W
Rabbits
(
13/
group)

Purity:
0.03%,
0.3%,
and
3%
LOEL
(
maternal
toxicity,
mice):
0.3%
(
50
mg/
kg/
d)
LOEL
(
maternal
toxicity,
rats):
3.0%
(
60
mg/
kg/
d)
LOEL
(
maternal
toxicity,
rabbits):
0.3%
(
9.0
mg/
kg/
d)

NOEL
(
maternal
toxicity,
mice):
0.03%
(
5.0
mg/
kg/
d)
NOEL
(
maternal
toxicity,
rats):
0.3%
(
6.0
mg/
kg/
d)
NOEL
(
maternal
toxicity,
rabbits):
0.03%
((
0.9
mg/
kg/
d)

LOEL
(
developmental
toxicity):
0.3%
(
50
mg/
kg/
d)
LOEL
(
developmental
toxicity):
3.0%
(
60
mg/
kg/
d)
LOEL
(
developmental
toxicity):
3.0%
(
90
mg/
kg/
d)

NOEL
(
developmental
toxicity):
0.03%
(
5.0
mg/
kg/
d)
NOEL
(
developmental
toxicity):
0.3%
(
6.0
mg/
kg/
d)
NOEL
(
developmental
toxicity):
0.3%
(
9.0
mg/
kg/
d)
30
of
42
Guideline
No./
Study
Type
MRID
No./
Reference
Information/
Study
Classification
Dosing
and
Animal
Information
Results
Marked
local
skin
reaction,
irritability,
weight
loss
and
failure
to
maintain
or
establish
pregnancy
was
evident
in
mice
treated
with
LAS
3%
soap,
3
or
30%:
marked
local
reaction
and
weight
loss
also
occurred
in
rabbits
receiving
LAS
3%.
Moderate
maternal
toxicity
was
observed
among
mice
treated
with
LAS,
0.3%
and
mild
maternal
toxicity
in
rats
receiving
LAS
3%
or
soap
30%
and
rabbits
receiving
LAS
0.3%.
Effects
on
litter
parameters
were
dose­
dependent,
causing
marked
maternal
toxicity
in
mice,
the
principal
higher
fetal
loss,
reduction
in
viable
litter
size.
LAS
at
3%
showed
marked
maternal
toxicity
in
the
rabbit
The
moderate
maternal
toxicity
of
LAS,
0.3%
in
the
mouse
correlated
with
a
higher
incidence
of
embryonic
deaths
and
lower
litter
size
but
only
the
former
differed
significantly
from
the
corresponding
control
value.

870.3700a
Developmental
Toxicity
(
rodent)
Sato
et
al.
(
1972)
Studies
on
the
Toxicity
of
Synthetic
Detergents:
(
III),
Examination
of
Teratogenic
Effects
of
Alkylbenzene
Sulfonates
Spread
on
the
Skin
of
Mice.
Ann.
Rep.
Tokyo
Metrop.
Res.
Lab.
Public
Health
24:
441­
448.
(
HERA)

Open
Literature
LAS
was
applied
to
the
skin
of
female
mice
daily
on
days
0
through
13
of
pregnancy
with
a
single
LAS
dose
of
110
mg/
kg
bw/
d.
Control
group
not
specified.

F
Mouse
Purity:
Not
Reported
NOAEL
(
maternal):
110
mg/
kg
bw/
d
No
abnormalities
were
seen
in
the
dam
or
foetuses.

870.3700a
Developmental
Toxicity
(
rodent)
Shiobara
S.,
Imahori
A.
(
1976)
Effects
of
LAS
Orally
Administered
to
Pregnant
Mice
on
the
Pregnant
Mice
and
their
Fetuses.
J.
Food
Hyg.
Soc.
Jpn.
(
Shokuhin
Eiseigaku
Zasshi)
17(
4):
295­
301.

Open
Literature
LAS
was
administered
by
gavage
at
doses
of
10,
100,
and
300
mg/
kg
bw/
d
at
day
6
through
15
of
gestation
ICR­
SLC
Mouse
(
25­
33/
dose)

Purity:
Not
Reported
LOAEL
(
maternal):
10
mg/
kg
bw/
d
NOAEL
(
fetuses):
300
mg/
kg
bw/
d
1.
Marked
maternal
and
embryonic
toxicities,
such
as
maternal
death,
premature
delivery,
total
litter
loss
and
high
fetal
death
rate,
were
observed
at
300
mg/
kg
group.

2.
Slight
suppression
of
maternal
body
weight
gain
and
slight
body
weight
suppression
of
live
fetuses
were
observed
in
each
treated
group.

3.
External
malformations
such
as
cleft
palate
and
exencephaly
were
observed
sporadically
both
in
the
control
and
the
treated
groups.
However,
the
incidence
of
these
malformations
was
not
significant,
and
considered
to
be
within
the
spontaneous
incidence
of
ICR
mice.

870.3700a
Developmental
Toxicity
(
rodent)
Takahashi
et
al.
(
1975)
Teratogenicity
of
Some
Synthetic
Detergent
and
LAS.
Ann.
Rep.
Tokyo
Metrop.
Res.
Lab.
Public
Health
26(
2):
67­
78.
(
HERA)

Open
Literature
LAS
doses
of
40,
and
400
mg/
kg
bw/
d
were
administered
daily
from
day
0
to
day
6
of
pregnancy
or
from
day
7
to
13
of
pregnancy
by
gavage
Mouse
(
13­
14/
group)

Purity:
not
reported
NOAEL
(
maternal):
40
mg/
kg
bw/
d
NOAEL
(
fetuses):
400
mg/
kg
bw/
d
At
400
mg/
kg
bw/
day,
the
pregnancy
rate
was
46.2%
compared
to
92.9%
in
the
controls.
There
was
no
increase
in
malformations.
Although
no
information
on
maternal
toxicity
is
available,
it
appears
likely
that
maternal
toxicity
was
present
at
the
high
dose
group.

870.3700a
Tiba
et
al.
(
1976)
Effects
of
LAS
on
Dam,
LAS
was
administered
in
NOAEL
(
maternal):
780
mg/
kg
bw/
d
NOAEL
(
fetuses):
780
mg/
kg
bw/
d
31
of
42
Guideline
No./
Study
Type
MRID
No./
Reference
Information/
Study
Classification
Dosing
and
Animal
Information
Results
Developmental
Toxicity
(
rodent)
Fetus,
and
Newborn
Rat.
J.
Food
Hyg.
Soc.
Jpn.
(
Shokuhin
Eiseigaku
Zassh)
17(
1):
66­
71.
(
HERA)

Open
Literature
the
diet
at
doses
of
80
and
780
mg/
kg
bw/
d
from
day
0
to
20
of
gestation
F
Rat
(
16/
dose)

Purity:
Not
Reported
At
780
mg/
kg
bw/
day
there
were
no
abnormalities
in
the
body
weight
gains
of
the
dams,
or
in
the
occurrence
and
maintenance
of
pregnancy.
The
values
of
the
litter
parameters
did
not
differ
from
those
of
the
controls
and
there
was
no
evidence
of
teratogenicity.
The
number
of
offsprings
was
rather
low
in
the
highest
dose
group,
and
the
weaning
rate
of
78.3%
was
lower
than
the
100%
rate
observed
in
the
controls.
However,
there
were
no
abnormalities
in
body
weight
gain,
organ
weights
or
functions
in
the
offsprings.

Reproduction
Toxicity
870.3800
Reproduction
MRID
43498416
Buehler,
E.,
Newmann,
E.,
and
King,
W.
(
1971)
Two
Year
Feeding
and
Reproduction
Study
in
Rats
with
Linear
Alkylbenzene
Sulfonate
(
LAS).
Tox.
Appl.
Pharm.
18:
83­
91.
(
HERA)

Acceptable
Guideline
LAS
was
administered
in
the
diet
at
doses
of
0,
0.02,
0.1,
and
0.5%
,
equivalent
to
(
0,
10,
50,
250
mg/
kg
bw/
day)
for
84
days.

Weanling
Charles
River
CD
Rat
(
20/
sex/
dose)

Purity:
98.1%
NOAEL
Parental:
250
mg/
kg
bw/
day
NOAEL
Offspring:
50
mg/
kg/
d.

The
LOAEL
of
250
mg/
kg/
day
in
the
offspring
is
due
to
slight
(
non­
significant)
changes
in
hematology
and
histopathology
and
slight
decrease
in
day
21
body
weights.

870.3800
Reproduction
Endo
et
al.
(
1980)
Studies
of
the
Chronic
Toxicity
and
Teratogenicity
of
Synthetic
Surfactants,
Ann.
Rep.
Tokyo
Metrop.
Res.
Inst.
Environ.
Prot.
(
Tokyo
Kogai
Kenkyujo
Nempo),
236­
246.
(
HERA)

Open
Literature
LAS
was
administered
at
70
mg/
kg
bw/
day
in
the
drinking
water
in
a
four
generation
rat
study.

M/
F
Wistar
Rat
Purity:
Not
Reported
NOAEL:
>
70
mg/
kg
(
only
dose
tested)

No
effects
of
LAS
administration
were
observed
870.3800
Reproduction
Palmer
et
al.
(
1974)
Effect
of
CLD
Reproductive
Function
of
Multiple
Generations
in
the
Rat,
Report
LFO10/
731029,
Unpublished
results.
(
HERA)

Open
Literature
A
commercial
light
duty
liquid
detergent
of
LAS
(
17%)
and
alkyl
ethoxylate
sulphate
(
7%)
was
continuously
administered
in
the
diet
for
three
generations
60
days
prior
to
mating
at
concentrations
of
0,
40,
200,
and
1000
mg/
kg
bw/
d.
The
corresonding
administration
of
LAS
was
of
0,
6.8,
34,
and
170
mg/
kg
bw/
d.

Rat
Purity:
17%
NOAEL:
170
mg/
kg
bw/
d
Among
parental
animals
over
the
three
generations
there
were
no
signs
of
adverse
effects
of
treatment.
Food
consumption
and
bodyweight
changes
showed
no
consistent
relationship
to
dosage.
Necroscopy
revealed
no
changes
due
to
treatment.
The
mating
performance,
the
pregnancy
rate
and
the
duration
of
gestation
were
unaffected.
Among
litter
parameters,
organ
weight
analysis,
histopathology
and
skeletal
staining
of
representative
young
from
the
F3b
generation
revealed
no
changes
that
could
be
conclusively
related
to
treatment.

Chronic
Toxicity
870.4100a
Chronic
Toxicity
Taniguchi
et
al.
(
1978)
Results
of
Studies
on
Synthetic
Detergents.
Tokyo,
Science
and
LAS
were
applied
to
the
dorsal
skin
of
rats
three
times
per
week
at
doses
of
1,
5,
or
25
mg/
rat
for
24
Treatment
had
no
effect
on
organ
weights
or
histopathological
appearance,
and
there
was
no
evidence
of
toxicity
or
carcinogenicity.
32
of
42
Guideline
No./
Study
Type
MRID
No./
Reference
Information/
Study
Classification
Dosing
and
Animal
Information
Results
(
rodent)
Technology
Agency,
Research
and
Coordination
Bureau,
pp.
18­
54.
(
WHO
1996)

Open
Literature
months.
Each
application
was
washed
from
the
skin
with
warm
water
after
24
hours.

SLC­
Wistar
Rats
Purity:
19.7%
a.
i.

870.3100
Chronic
Toxicity
(
rodent)
Yoneyama
et
al.
(
1976)
Subacute
Toxicity
of
LAS,
Ann.
Rep.
Tokyo
Metrop.
Res.
Lab.
Public
Health27(
2):
105­
112,
See:
IPCS,
1996.
(
HERA)

Open
Literature
LAS
was
administered
in
the
diet
at
concentrations
of
500
and
1000
mg/
kg
bw/
d
and
in
drinking
water
at
concentrations
of
100,
250,
600
mg/
kg
bw/
d
for
males
and
100,
250,
900
mg/
kg
bw/
d
for
females
for
9
months
Mouse
(
8
or
9/
sex/
dose)

Purity:
Not
Reported
LOAEL:
500
mg/
kg
bw/
d
(
in
diet)
NOAEL:
250
mg/
kg
bw/
d
(
in
water)

LAS
in
diet:
in
the
mice
given
500
mg/
kg
bw/
day,
body
weight
gain
was
not
suppressed,
but
the
weight
of
the
liver
increased
in
male
and
female
mice.
Enzymatic
examinations
revealed
significant
decreases
in
LDH
of
the
liver
and
in
acid
phosphatase
of
the
kidneys
in
the
male
mice.

LAS
in
drinking
water:
body
weight
was
depressed
at
the
highest
dose
for
male
and
females,
increase
in
liver
weight
in
females,
significant
decreases
in
renal
Na,
KATPase

870.3100
Chronic
Toxicity
(
rodent)
Yoneyama
et
al.
(
1976)
Subacute
Toxicity
of
LAS,
Ann.
Rep.
Tokyo
Metrop.
Res.
Lab.
Public
Health27(
2):
105­
112,
See:
IPCS,
1996.
(
HERA)

Open
Literature
LAS
was
administered
for
9
months
in
the
drinking
water
at
doses
of
85,
145,
430
mg/
kg
bw/
day
M/
F
Wistar
Rat
Purity:
Not
Reported
NOAEL:
85
mg/
kg
bw/
d
LOAEL:
145
mg/
kg
bw/
d
Haematological
examination
revealed
no
significant
changes
in
any
experimental
group
and
no
organ
weight
changes
were
observed.
Body
weight
gain
was
suppressed
in
the
males
of
the
highest
dose
group
and
also
serum­
biochemical
and
enzymatic
parameters
of
the
liver
and
kidney
were
affected.
A
significant
decrease
in
renal
Na,
K­
ATPase
was
seen
in
the
group
given
145
mg/
kg
bw/
day
of
LAS.

870.4100a
Chronic
Toxicity
(
rodent)
Yoneyama
et
al.
(
1972)
Studies
on
the
Toxicity
of
Synthetic
Detergents.
(
II)
Subacute
Toxicity
of
Linear
and
Branched
Alkyl
Benzene
Sulfonates
in
Rats.
Ann
Rep
Tokyo
Metrop
Res
Lab
Public
Health,
24:
409­
440.

Open
Literature
Technical­
grade
LAS
was
administered
in
the
feed
for
6
months
at
a
concentration
of
0,
0.07,
0.2,
0.6,
or
1.8%

Wistar
SLC
Strain
Rat
(
10/
sex/
dose)

Purity:
Not
Reported
NOAEL:
0.07%
(
40
mg/
kg
bw/
day)

At
1.8%,
diarrhea,
decrease
in
body
weight
gain
and
tissue
damage
in
caecum
liver
and
kidney
were
observed.
The
damage
to
the
kidney
was
especially
remarkable.

At
0.6%
of
the
LAS
or
ABS,
the
adverse
effects
observed
were
a
slight
decrease
of
body
weight,
increase
of
ceacum
weight,
increased
activity
of
alkaline
phosphatase,
decrease
of
total
protein
in
blood,
and
the
tissue
damage
in
the
kidney.

At
0.2%
of
the
LAS
or
ABS,
an
increase
of
caecum
weight
and
a
slight
damage
to
the
kidney
were
observed.

Carcinogenicity
870.4200a
Oncogenicity
(
Rat)
MRID
43498416
Buehler,
E.,
Newmann,
E.,
and
King,
W.
(
1971)
Two
Year
Feeding
and
Reproduction
Study
in
Rats
with
Linear
Alkylbenzene
Sulfonate
(
LAS).
Tox.
Appl.
Pharm.
18:
83­
91.
LAS
was
administered
in
the
diet
at
doses
of
10,
50,
and
250
mg/
kg/
day
for
2
years
Weanling
Charles
River
CD
Rats
(
50/
sex/
group)

Purity:
Not
Reported
Negative
at
250
mg/
kg/
day
(
HDT)
33
of
42
Guideline
No./
Study
Type
MRID
No./
Reference
Information/
Study
Classification
Dosing
and
Animal
Information
Results
(
HERA)

Acceptable
Guideline
870.4200a
Oncogenicity
(
Rat)
Endo
et
al.
(
1980)
Studies
of
the
Chronic
Toxicity
and
Teratogenicity
of
Synthetic
Surfactants,
Ann.
Rep.
Tokyo
Metrop.
Res.
Inst.
Environ.
Prot.
(
Tokyo
Kogai
Kenkyujo
Nempo),
236­
246.
(
HERA)
Open
Literature
LAS
was
administered
in
the
drinking
water
at
the
dose
of
200
mg/
kg
bw/
d
62
M/
F
Wistar
Rat
Purity:
38.74%
a.
i.
The
administration
of
LAS
had
no
effect
on
the
intake
of
water,
mortality,
body
weight
gain,
or
general
condition.
In
pathological
examinations,
looseness,
atrophy,
and
fatty
change
of
the
hepatic
cells
in
the
liver
were
found
in
the
experimental
control
group
at
6
months,
together
with
significant
increases
in
GOT,
GTP
and
bilirubin.
In
hematological
examinations
no
effects
due
to
LAS
were
observed.

870.4200a
Oncogenicity
(
Rat)
Fujii
et
al.
(
1977)
Pathological
Examination
of
Rats
Fed
with
LAS
for
their
Lifespan,
Ann.
Rep.
Tokyo
Metrop.
Res.
Lab.
Public
Health
28(
2):
85­
108.
(
HERA)

Yoneyama
et
al.
(
1977)
Toxicity
of
LAS
by
Dietary
Administration
for
Life­
Span
to
Rats,
Ann.
Rep.
Tokyo
Metrop.
Res.
Lab.
Public
Health
28(
2):
73­
84.
(
HERA)

Open
Literature
LAS
was
administered
in
the
feed
at
a
concentration
of
0.04,
0.16,
and
0.60%
for
24
months
or
lifespan
Wistar
Weanling
Rat
(
15/
sex/
dose)

Purity:
Not
Reported
Histopathological
examination
revealed
that
there
was
no
evidence
of
a
treatment­
related
effect
on
any
tissue
examined.
Whereas
a
variety
of
tumors
were
observed
in
both
linear
alkylbenzene
sulfonate
treated
and
control
rats,
none
was
attributed
for
the
exposure
to
linear
alkylbenzene
sulfonate.
There
was
no
relationship
among
the
dosage
groups,
sex,
type
of
tumor,
or
the
site
of
occurrence.

870.4200a
Oncogenicity
(
Rat)
MRID
43498420
Takahasi
et
al.
(
1969)
Effect
of
Alkylbenzenesulfonate
as
a
Vehicle
for
4­
Nitroquinoline­
1­
Oxide
on
Gastric
Carcinogenesis
in
Rats.
GANN:
8,
241­
261.

Acceptable
Guideline
For
560
days;
Group
I
(
79
rats):
1
mg
4­
NQO
and
80
mg
SDDBS
2­
3x
per
week
for
18
weeks;
Group
I'
(
17
rats):
same
as
Group
1,
but
fasted
for
12
hours
prior
to
dosing,;
Group
II
(
37
rats):
1
mg
4­
NQO
only;
Group
III
(
28
rats):
80
mg
SDDBS
only
97
M
Wistar
Rats
Purity:
Not
Reported
In
Groups
I
and
I',
the
presence
of
SDDBS
shifts
the
incidence
of
benign
papillomas
to
malignant
papillomas
of
the
forestomach
and
the
incidence
of
adenocarcinoma
and
sarcoma
of
the
stomach
were
increased
in
comparison
to
Group
II
with
only
4­
NQO.
The
administration
of
SDDBS
by
itself
has
no
effect
on
gastric
tumors
(
Group
III).
The
study
authors
concluded
that
the
increased
carcinogenicity
produced
by
SDDBS
was
due
to
the
better
uptake
of
4­
NQO
via
LAS's
surfactive/
detersive
effects
on
the
protective
mucous
barrier
which
is
normally
found
in
the
glandular
stomach
and
other
gastric
compartments
of
the
rat.
The
effect
of
SDDBS
was
physical
rather
than
chemical
in
promoting
the
increased
tumorigenicity.

870.4200a
Oncogenicity
(
Rat)
MRID
43498419
Takahasi
et
al.
(
1970)
Effect
of
4­
Nitroquinoline­
1­
Oxide
with
Alkylbenzenesulfonate
on
Gastric
Carcinogenesis
in
Rats.
GANN:
61,
27­
33.

Acceptable
Guideline
Rats
were
divided
into
three
groups
and
gavaged
with
the
following
regimen
for
560
days:
Group
I
(
37
rats)
­
1
mg
4­
NQO
+
80
mg
SDDBS
+
20
mg
ethanol
in
a
1
ml
gavage
for
18
weeks;
Group
II
(
13
rats)
­
4­
NQO
and
ethanol
for
18
weeks;
Group
III
(
13
rats)
­
SDDBS
+
ethanol
for
18
weeks
Survival:
Mortality
was
59%
in
Group
I,
31%
in
Group
II,
and
23%
in
Group
III
Tumors:
Group
III
­
no
gastric
tumors;
Group
II
­
9
benign
papillomas
of
forestomach;
Group
I
­
8
benign
papillomas
of
forestomach,
2
malignant
papillomas
of
forestomach,
1
hemangiosarcoma
of
forestomach.
In
glandular
stomach,
2
adenocarcinomas,
1
hemangiosarcoma,
1
hemangioma,
5
squamous
cell
carcinomas,
and
2
rats
exhibited
atrophic
gastritis.

The
increased
toxicity
in
Group
I
produced
increased
34
of
42
Guideline
No./
Study
Type
MRID
No./
Reference
Information/
Study
Classification
Dosing
and
Animal
Information
Results
64
M
Motoyama
Strain
Rat
Purity:
Not
Reported
mortality
and
increased
numbers
of
malignant
tumors.
The
role
of
SDDBS
in
the
tumorigenesis
of
4­
NQO
was
to
promote
increased
absorption
of
4­
NQO
through
the
forestomach
and
glandular
stomach.

870.4200a
Oncogenicity
(
Rat)
MRID
43498421,
­
22
Takahasi
et
al.
(
1973)
Carcinogenic
Effect
of
N­
Methyl­
N'­
Nitro­
NNitrosoguanidine
with
Various
Kinds
of
Surfactant
in
the
Glandular
Stomach
of
Rats.

Acceptable
Guideline
SDDBS
was
administered
to
5
groups
of
rats:
(
I)
13
rats
received
0.1g
of
MNNG
+
4000
mg
Tween
60
per
L
of
drinking
water
for
36
weeks;
(
II)
16
rats
received
0.1
g
MNNG
+
2000
mg
nonipol
per
L
of
drinking
water
for
36
weeks;
(
III)
15
rats
received
0.1
g
of
MNNG
+
1000
mg
branched
("
hard")
SDDBS
per
L
of
drinking
water
for
63
weeks;
(
IV)
10
rats
received
0.1
g
MNNG
+
1000
mg
of
linear
("
soft")
SDDBS
per
L
of
drinking
water
for
63
weeks;
(
V)
14
rats
received
o.
1
g
MNNG
per
L
of
drinking
water
for
63
weeks
M
Wistar
Rats
Purity:
Not
Reported
Survivial
was
100%
in
Groups
I,
III,
and
IV,
and
93%
and
94%
in
Groups
V
and
II,
respectively.

The
Group
I
and
II
rats
had
more
tumors
than
the
controls
(
Group
V),
whereas,
the
rats
in
Group
III,
("
hard"
SDDBS,
and
particularly,
Group
IV
(
linear
"
soft"
SDDBS)
had
the
fewest
tumors
in
comparison
to
controls.

870.4200a
Oncogenicity
(
Rat)
Tiba
S
(
1972)
Studies
on
the
Acute
and
Chronic
Toxicity
of
LAS,
J.
Food
Hyg.
Soc.
Jpn.
(
Shokuhin
Eiseigaku
Zasshi)
13(
6):
509­
516.
(
HERA)

Open
Literature
LAS
was
administered
in
drinking
water
for
2
years
at
doses
of
20,
100,
and
200
mg/
kg
bw/
d
M
Wistar
Rat
(
20/
group)

Purity:
Not
Reported
There
were
no
changes
due
to
the
administration
of
LAS
in
regard
to
growth,
mortality,
the
weight
of
major
organs,
or
histopathological
findings
Mutagenicity
870.5100
Bacterial
reverse
mutation
test
Huls,
Report
No.
AM­
93/
12,
Unpublished
data,
1993.
(
As
cited
in
HERA­
2004)

Open
Literature
LAS
was
tested
at
8­
5000
ug/
plate
with
and
without
metabolic
activation.
The
cytotoxicity
concentration
was
>
5000
ug/
plate.

Salmonella
typhimurium,
strains
TA
98,
TA
100,
TA
1535,
TA
1537,
and
TA
1538
Purity:
Not
Reported
Negative
results
870.5100
Bacterial
reverse
mutation
test
MRID
43498429
Inoue
et
al.
(
1980)
Studies
of
In
Vitro
Cell
Transformation
and
Mutagenicity
by
Surfactants
and
other
Compounds,
Food.
Cosmet.
Toxicol
18:
289­
296.
(
HERA)
SDDBS
was
tested
at
cytotoxic
levels
or
limit
concentrations
of
2,000­
30,000
ug/
plate
for
2
days
(
Salmonella)
or
8
days
(
SHE)

Strain:
Salmonella
typhimurium
­
TA
98
and
TA
100
cells
and
Negative
(
both
with
and
without
S­
9
metabolic
activation)
35
of
42
Guideline
No./
Study
Type
MRID
No./
Reference
Information/
Study
Classification
Dosing
and
Animal
Information
Results
Acceptable
Guideline
Embryonic
Syrian
Golden
Hamster
cells
(
SHE)

Purity:
Not
Reported
870.5100
Bacterial
reverse
mutation
test
Sunakawa
et
al.
(
1981)
Studies
on
the
Mutagenicity
of
Surfactants
Following
Activation
with
Various
Liver
Homogenates
(
S­
9)
and
Mutagenicity
in
the
Presence
of
Norharman,
Hyg.
Chem.
(
Eisei
Kagaku)
27(
4):
204­
211,
See:
WHO,
1996.

Open
Literature
LAS
was
tested
at
up
to
500
ug/
plate
Salmonella
typhimurium
Purity:
Not
Reported
Negative
Results
870.5300
In
Vitro
mammalian
cell
gene
mutation
test
Inoue,
K.
et
al.
(
1977)
Osaka­
furitsu
Koshu
Eisei
Kenkyusho
Kenkyu
Hokoku,
Shokuhin
Eisei
Hen
8:
25­
8.
(
HERA)

Open
Literature
Sodium
alkylbenzenesulfonate
was
added
to
culture
at
62.5
ug/
ml
and
125
ug/
l
Hamster
Lung
Cell
Purity:
Not
Reported
At
62.5
ug/
ml:
induced
cell
mutation,
no
effect
on
sister
chromatid
exchange
At
125
ug/
ml:
destroyed
the
cells
completely
870.5300
In
Vitro
cell
transformation
MRID
No.
43498427
K.
Inoue
et
al
(
1980)
Food
Cosmetic
Toxicol.
18:
289­
296
Acceptable
Open
Literature,
Duplicate
primary
cultures
of
embryonic
SHE
and
Salmonella
typhimurium
strain
TA
98
and
TA
100
cells
were
exposed
to
SDDBS
and
positive
and
negative
controls
for
8
days.
SDDBS
was
negative
for
transformation
up
to
cytotoxic
levels
and
did
not
induce
mutation
in
either
strains
of
Salmonalla
when
allplied
up
to
cytotoxic
levels
or
limit
concentration
of
2000­
3000
ug/
plate.

SDDBS
was
tested
negative
at
cytotoxic
levels
or
limit
concentrations
(
both
with
and
without
S­
9
metabolic
activation)
of
2,000­
30,000
ug/
plate
for
2
days
(
Salmonella)
or
8
days
(
SHE)

870.5385
Mammalian
bone
marrow
chomosomal
aberration
test
Inoue
K,
et
al.
(
1979)
In
vivo
Cytogenetic
Tests
of
Some
Synthetic
Detergents
in
Mice,
Ann.
Rep.
Osaka
Perfect.
Inst.
Public
Health
8:
17­
24
(
in
Japanese),
See:
IPCS,
1996.
(
HERA)

Open
Literature
LAS
was
administered
at
doses
of
200,
400,
and
800
mg/
kg
bw/
d
by
gavage
for
1
and
5
days
M
Mouse
Purity:
Not
Reported
There
was
no
significant
difference
in
the
incidence
of
chromosomal
aberrations
between
any
of
the
groups
870.5385
Mammalian
bone
marrow
chomosomal
aberration
test
Inoue,
K.
et
al.
(
1977)
In
Vivo
Cytogenetic
Tests
of
Some
Synthetic
Detergents
in
Mice.
Ann
Rep
Osaka
Prefect
Inst
Public
Health,
8:
17­
24.
(
HERA)

Open
Literature
LAS
was
administered
at
a
dose
of
200,
400,
and
800
mg/
kg
bw/
d
by
gavage
for
5
days.
One
commercial
preparation
containing
19.0%
LAS
was
also
given,
at
a
dose
of
800,
1600,
or
3200
mg/
kg
bw,
and
another
containing
17.1%
LAS
at
a
dose
of
1000,
2000,
or
4000
mg/
kg
bw
once
only
by
gavage.

M
ICR:
JCL
Mouse
Purity:
Not
Reported
There
was
no
significant
difference
between
any
of
the
groups
given
LAS
and
the
negative
control
group
in
the
incidence
of
chromosomal
aberrations
36
of
42
Guideline
No./
Study
Type
MRID
No./
Reference
Information/
Study
Classification
Dosing
and
Animal
Information
Results
870.5385
Mammalian
bone
marrow
chomosomal
aberration
test
MRID
43498428
J.
Hope
(
1977)
Absence
of
Chromosome
Damage
in
the
Bone
Marrow
of
Rats
Fed
Detergent
Actives
for
90
Days.
Mutation
Research,
56:
47­
50.

Acceptable
Guideline
SDDBS
was
administered
in
the
diet
for
90
days
at
0,
280,
and
565
mg/
kg
bw/
d
Colworth/
Wistar
Weanling
Rat
(
6/
sex/
dose)

Purity:
Not
Reported
All
test
preparations
were
negative
for
increased
chromosomal
damage
over
controls.

870.5385
Mammalian
bone
marrow
chomosomal
aberration
test
Masabuchi
et
al.
(
1976)
Cytogenetic
Studies
and
Dominant
Lethal
Tests
with
Long
Term
Administration
of
Butylated
Hydroxytoluene
(
BHT)
and
LAS
in
Mice
and
Rats,
Ann.
Rep.
Tokyo
Metrop.
Res.
Lab.
Public
Health
27(
2):
100­
104.
(
HERA)

Open
Literature
LAS
was
administered
in
the
diet
for
9
months
at
a
dose
of
0.9%
in
rats
(
450
mg/
kg
bw/
d)
and
in
mice
(
1170
mg/
kg
bw/
d)

Male
Rat
and
Male
Mouse
Purity:
Not
Reported
There
were
no
significant
differences
in
the
incidences
of
chromosomal
aberrations
between
the
experimental
and
control
groups
870.5395
Mammalian
erthrocyte
micronucleus
test
Kishi
et
al.
(
1984)
Effects
of
Surfactants
on
Bone
Marrow
Cells,
Bull.
Kanagawa
Public
Health
Lab.
14:
57­
58.
(
HERA)

Open
Literature
LAS
was
administered
as
a
single
intraperitoneal
injection
at
a
dose
of
100
mg/
kg
bw
3
M
ddY
Mice
Purity:
Not
Reported
There
were
no
differences
in
the
incidences
of
polychromatic
erythrocytes
with
micronuclei
in
the
bone
marrow
cells
between
the
treated
group
and
the
control
group
870.5395
Mammalian
erthrocyte
micronucleus
test
Koizumi
et
al.
(
1985)
Implantation
Disturbance
Studies
with
LAS
in
Mice,
Arch.
Environ.
Contam.
Toxicol.
14:
73­
81.
(
HERA)

Open
Literature
LAS
were
administered
as
a
single
oral
dose
of
2
mg
to
pregnant
mice
on
day
3
of
gestation.
On
day
17
of
gestation,
each
animal
received
a
subcutaneous
dose
of
1,
2,
or
10
mg
and
were
killed
24
h
later.

Pregnant
ICR
Mice
Purity:
Not
Reported
There
was
no
difference
among
treated
groups
in
the
incidence
of
polychromatic
erythrocytes
with
micronuclei
in
maternal
bone
marrow
or
fetal
liver
or
blood.
No
mutagenetic
effect
was
found
in
any
of
the
groups.

870.5450
Rodent
dominant
lethal
assay
Masubuchi
MA
et
al.
(
1976)
Cytogenetic
Studies
and
Dominant
Lethal
Tests
with
Long
Term
Administration
of
Butylated
Hydroxytoluene
(
BHT)
and
Linear
Alkylbenzene
Sulfonate
(
LAS)
in
Mice
and
Rats.
Ann
Rep
Tokyo
Metrop
Res
Lab
Public
Heath,
A
diet
containing
0.6%
LAS
at
300
mg/
kg
bw/
d
was
administered
to
mice
for
9
months.
Each
of
the
male
mice
was
then
mated
with
two
female
mice
that
had
not
been
given
LAS,
and
11
of
the
14
females
became
pregnant.
The
pregnant
mice
were
laparotomized
on
day
13
of
gestation
There
were
no
significant
differences
in
fertility,
mortality
of
ova
and
embryos,
the
number
of
surviving
fetuses,
or
the
index
of
dominant
lethal
induction
(
Roehrborn)
between
the
experimental
and
control
groups.
37
of
42
Guideline
No./
Study
Type
MRID
No./
Reference
Information/
Study
Classification
Dosing
and
Animal
Information
Results
27(
2):
100­
104.

(
HERA)

Open
Literature
7
M
ICR:
JCL
Mice
Purity:
Not
Reported
Metabolism
870.7485
General
Metabolism
MRID
43498410
Creswell
et
al.
(
1978)
Toxicology
Studies
of
Linear
Alkylbenzene
Sulfonate
(
LAS)
in
Rhesus
Monkeys
II.
The
Disposition
of
C14­
LAS
After
Oral
or
Subcutaneous
Administration.
Toxicology,
11:
5­
17.

Acceptable
Guideline
Single
oral
doses
of
C14­
LAS
(
SDDBS;
25
ucuries)
were
administered
to
each
animal,
following
2­
3
weeks
between
dose
levels,
at
levels
of
30,
150,
and
300
mg/
kg.
Following
2­
3
weeks
after
the
last
single
oral
dose,
each
monkey
received
7
consecutive
daily
oral
doses
of
30
mg/
kg/
d
of
C14­
LAS.

2
M/
2
F
Rhesus
Monkeys
Purity:
Not
Reported
After
single
30
mg/
kg
doses
the
radioactivity
was
rapidly
excreted,
mostly
during
the
first
24
hours.
Feces
and
urine
contained
23.1%
and
71.2%,
respectively,
in
the
first
5
days
after
oral
dosing.
Plasma
concentrations
were
comparable
after
the
oral
doses
and
averaged
34,
41,
and
36
u/
ml,
respectively.
Peak
plasma
concentrations
increased
proportional
to
the
dose
and
were
0.16,
0.72,
1.13
u/
ml,
respectively.
In
urine
samples
analyzed
for
metabolites,
there
was
no
unchanged
SDDBS
and
the
5
metabolites
detected
were
polar,
but
were
not
sulphate
or
glucuronide
conjugates.

870.7485
General
Metabolism
Lay
JP,
et
al.
(
1983)
Toxicol.
Letters
17
(
1­
2):
187­
192
Open
Literature
(
14)
C­
labeled
sodium
dodecylbenzenesulfonate
was
administered
daily
in
the
diet
at
a
concentration
of
1.4
mg/
kg
for
5
weeks
M
Rat
Purity:
not
reported
From
a
total
uptake
of
1.213
+
or
­
0.08
mg/
animal
of
DBS,
81.8%
was
excreted
during
the
dosing
period:
52.4%
in
feces
and
29.4%
in
urine.
Low
levels
of
(
14)
C­
DBS­
derived
residues
were
detected
in
all
tissues
analyzed
on
day
35
of
the
study.
Following
1
week
on
a
normal
diet,
only
7.8%
of
the
nominally
stored
amount
of
(
14)
C
was
found
in
the
excreta.

870.7485
General
Metabolism
Sunakawa
et
al.
(
1979)
Yakuzaigaku
39
(
2):
59­
68
Open
Literature
Sodium­
paradodecylbenzenesulfonate
Rat
Purity:
Not
Reported
Blood
levels
were
max
at
2
hr,
negligible
at
48
hr
Excretion
rate
of
radioactive
label
was
99.4%
after
48
hr
870.7485
General
Metabolism
The
Royal
Society
of
Chemistry.
(
1981)
Foreign
Compound
Metabolism
in
Mammals.
Volume
6:
A
Review
of
the
Literature
Published
during
1978
and
1979.
London:
The
Royal
Society
of
Chemistry,
p.
354.

Open
Literature
(
35)
S­
labeled
sodium
dodecylbenzenesulfonate
was
administered
as
a
single
oral
dose
Rat
Purity:
Not
Reported
Rats
excreted
64%
and
24%
of
the
dose
in
urine
and
feces,
respectively
870.7485
General
Metabolism
The
Royal
Society
of
Chemistry.
(
1981)
Foreign
Compound
Metabolism
in
Mammals.
Volume
6:
A
Review
of
the
Literature
Published
during
1978
and
1979.
London:
The
Royal
Society
of
Chemistry,
p.
354.
Repeated
doses
of
(
14)
Clabeled
alkylbenzenesulfonate
were
orally
administered
Rhesus
Monkey
Purity:
Not
Reported
Radioactivity
did
not
accumulate
in
the
tissues
870.7485
MRID
43498431
LAS­
S35
was
administered
The
rate
and
distribution
of
the
excreted
dose
was
38
of
42
Guideline
No./
Study
Type
MRID
No./
Reference
Information/
Study
Classification
Dosing
and
Animal
Information
Results
General
Metabolism
W.
Michael
(
1968)
Metabolism
of
Linear
Alkylate
Sulfonate
and
Alkyl
Benzene
Sulfonate.
Toxicol.
Appl.
Pharmacol.
12:
473­
485.

Acceptable
Guideline
orally
to
fasted
rats
at
doses
of
0.6,
1.2,
8,
and
40
mg
Charles
River
CD
M
Rat
Purity:
Not
Reported
independent
of
concentration.

Similar
levels
of
radioactivity
were
found
in
urine
and
feces
and
within
3
days,
85.2%
­
96.6%
of
the
label
was
recovered.

In
the
high
dose
rats,
no
detectable
radioactivity
was
found
in
the
carcasses
after
3
days.

Following
methylation,
one
urinary
metabolite
was
identified
as
4­(
4'­
methylsulfophenyl)
pentanoate.
LAS­
S35
in
the
feces
remained
unmetabolized.

Special
Studies
870.3700a
Developmental
Toxicity
(
rodent)
Koizumi
et
al.
(
1985)
Implantation
Disturbance
Studies
with
LAS
in
Mice,
Arch.
Environ.
Contam.
Toxicol.
14:
73­
81.
(
HERA)

Open
Literature
LAS
was
administered
as
a
single
oral
dose
of
350
mg/
kg
bw
on
day
3
of
gestation
Pregnant
ICR
Mice
Purity:
Not
Reported
LAS
was
not
detected
in
the
uterus
Other
Inoue
K,
T
Sunakawa.
(
1979)
Mutagenicity
Tests
of
Surfactants,
Jpn.
Fragr.
J.
38:
67­
75,
(
in
Japanese),
See:
IPCS,
1996.
(
HERA)

Open
Literature
LAS
tested
in
a
recombination
assay
at
concentrations
up
to
50
ug/
plate
Bacillus
subtilis
Purity:
99.5%
Negative
results
with
and
without
metabolic
activation
Other
Fujise,
H.
and
Aoyama,
M.
(
1984)
Nagoya
Med
J,
28
(
3­
4):
211­
5
Open
Literature
The
proliferation
rate
of
the
connective
tissue
was
examined
by
measuring
the
activity
of
proline
hydroxylase.
The
dorsal
neck
skin
of
rats
was
coated
with
sodium
laurylbenzenesulfonate
for
4
days,
and
on
the
5th
day,
the
enzyme
activity
in
the
skin
was
measured.

Rat
Purity:
Not
Reported
The
proline
hydroxylase
in
the
part
of
the
skin
coated
with
the
irritants
showed
clearly
higher
activity
than
normal
skin,
although
it
was
still
lower
than
the
injured
skin
region
prepared
as
a
positive
control.

Other
MRID
43498430
and
43498408
Kimura
et
al.
(
1982)
Mechanisms
of
Toxicities
of
Some
Detergents
Added
to
a
Diet
and
the
Ameliorating
Effects
of
Dietary
Fiber
in
the
Rat.
J.
Nutrit.
Science
and
Science
and
Vitaminology,
28:
483­
489.

Kimura
et
al.
(
1982)
Ringer's
bicarbonate
(
containing
sodium
lauryl
benzene
sulfonate)
at
0.5
ml/
min
was
used
to
perfuse
a
10
cm
length
of
jejunal
segment
for
150
minutes;
equilibrated
for
30
minutes
and
then
the
perfusates
were
collected
in
30
minute
aliqouts
for
120
minutes
M
Wistar
Rat
Purity:
0.5%
Alkaline
phosphatase
was
released
by
an
increase
of
15­
fold
in
comparison
to
Ringer's
alone
(
controls
without
added
sodium
lauryl
benzene
sulfonate)
and
3­
7
times
greater
than
other
surfactants
tested
in
Ringer's.
The
authors
conclude
that
SDDBS
has
an
exfoliative
effect
on
the
intestinal
brush
border
39
of
42
Guideline
No./
Study
Type
MRID
No./
Reference
Information/
Study
Classification
Dosing
and
Animal
Information
Results
Toxicity
for
Detergent
Feeding
and
Effect
of
the
Concurrent
Feeding
of
Dietary
Fiber
in
the
Rat.
Nutrition
Reports
International,
26(
2):
271­
279.

Acceptable
Guideline
Other
Oba
et
al.
(
1968)
Biochemical
Studies
of
n­
alpha­
olefin
sulfonates:
(
II)
Acute
Toxicity,
Skin
and
Eye
Irritation,
and
Some
Other
Physiological
Properties.
J
Jpn
Oil
Chem
Soc,
17
(
11):
628­
634.
(
EHC
169)

Open
Literature
Solutions
of
various
concentrations
of
LAS
were
mixed
with
red
blood
cells
from
rabbits
at
room
temperature
for
3
hours
Rabbit
Red
Blood
Cell
Purity:
Not
Reported
The
50%
haemolytic
concentration
of
LAS
was
9
mg/
litre
Other
Samejima
Y
(
1991)
Effects
of
Synthetic
Surfactants
and
Natural
Soap
on
the
Development
of
Mouse
Embryos
In
Vitro
and
the
Fertilizing
Capacity
of
Mouse
and
Human
Sperm.
J
Osaka
Univ
Med
Sch,
3
(
12):
675­
682.
(
EHC
169)

Open
Literature
Eggs
were
fertilized
in
vitro
and
incubated
in
culture
medium
containing
LAS
at
concentrations
between
0.015
and
0.03%.

F
B6C3F1
Mouse
Egg
Purity:
Not
Reported
Concentrations
of
LAS
less
than
0.025%:
Eggs
exposed
for
1
hr,
washed,
and
then
cultured
for
5
days
developed
normally
to
the
blastocyst
stage
Concentrations
of
LAS
higher
than
0.03%:
The
eggs
did
not
develop
beyond
the
one­
cell
stage
With
continuous
exposure
to
LAS
for
five
days,
a
concentration
of
0.01%
slightly
impaired
development
to
the
blastocyst
stage,
and
0.025%
prevented
development
to
the
one­
cell
stage
Other
Takahashi
et
al.
(
1974)
Inhibition
of
Thrombin
by
Linear
Alkylbenzene
Sulfonate
(
LAS).
Ann
Rep
Tokyo
Metrop
Res
Lab
Public
Health,
25:
637­
645.
(
HERA)

Open
Literature
Purified
LAS
at
various
concentrations
were
added
to
10
ul
of
plasma
from
rats
and
prothrombin
time
was
determined
M
Rat
Purity:
Not
Reported
Prothrombin
time
was
prolonged;
the
50%
inhibitory
concentration
was
about
0.6
mmol/
litre.
When
LAS
at
various
concentrations
were
added
to
a
mixture
of
1%
fibrinogen
and
thrombin,
the
time
of
formation
of
a
mass
of
fibrin
was
prolonged
by
inhibition
of
thrombin
activity.
The
50%
inhibitory
concentration
was
about
0.05
mmol/
litre.

Other
Yanagisawa
et
al.
(
1964)
Biochemical
Studies
of
Dodecylbenzene
Sulfonates;
Differences
Between
Soft
and
Hard
Detergents.
Jpn.
J
Public
Health,
11(
13):
859­
864.
(
EHC
169)

Open
Literature
The
haemolytic
action
of
LAS
was
investigated
by
mixing
red
blood
cells
from
rabbits
with
solutions
of
LAS
at
concentrations
of
1­
1000
mg/
litre
at
38
C
for
30
min
Rabbit
Red
Blood
Cell
Purity:
Not
Reported
Haemolysis
occurred
at
concentrations
>=
5
mg/
litre.
40
of
42
9.2
Summary
of
Toxicological
Dose
and
Endpoints
for
Linear
Alkylbenzene
Sulfonates
Table
3.
Summary
of
Toxicological
Dose
and
Endpoints
for
Alkylbenzene
Sulfonates
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
Special
FQPA
SF*,
endpoint
and
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
Acute
Dietary
(
All
populations)
No
endpoint
was
selected.
No
effects
are
attributable
to
a
single
dose.

Chronic
Dietary
(
All
populations)
Systemic/
Reproductive
NOAEL=
50
mg/
kg/
day
UF
=
100
Chronic
RfD
=
0.5
mg/
kg/
day
FQPA
SF
=
1X
cPAD
=
chronic
RfD
FQPA
SF
=
0.5
mg/
kg/
day
Systemic/
Reproductive
LOAEL
=
250
mg/
kg/
day
based
on
decreased
Day
21
female
pup
body
weight
(
Buehler,
E.
et
al.
1971.
Tox.
Appl.
Pharmacol.
18:
83­
91)

plus
LOAEL=
145
mg/
kg/
day
from
9
month
drinking
water
rat
study
based
on
decreased
body
weight
gain,
and
serum/
biochemical
and
enzymatic
changes
in
the
liver
and
kidney
(
Yoneyama
et
al.
1976
Ann.
Rep.
Tokyo
Metrop.
Res.
Lab.
Public
Health
27(
2):
105­
112)

plus
LOAEL=
114
mg/
kg/
day
(
0.2%)
based
on
increased
caecum
weight
and
slight
kidney
damage
in
a
6
month
rat
dietary
study
(
Yoneyama
et
al
1972
Ann.
Rep.
Tokyo
Metrop.
Res.
Lab.
Public
Health
24:
409­
440)
41
of
42
Table
3.
Summary
of
Toxicological
Dose
and
Endpoints
for
Alkylbenzene
Sulfonates
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
Special
FQPA
SF*,
endpoint
and
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
Short­
Term
Incidental
Oral
(
1­
30
days)
Oral
NOAEL=
50
mg/
kg/
day
Residential
LOC
for
MOE
=
100
Systemic/
Reproductive
LOAEL
=
250
mg/
kg/
day
based
on
decreased
Day
21
female
pup
body
weight
(
Buehler,
E.
et
al.
1971.
Tox.
Appl.
Pharmacol.
18:
83­
91)

plus
LOAEL=
145
mg/
kg/
day
from
9
month
drinking
water
rat
study
based
on
decreased
body
weight
gain,
and
serum/
biochemical
and
enzymatic
changes
in
the
liver
and
kidney
(
Yoneyama
et
al.
1976
Ann.
Rep.
Tokyo
Metrop.
Res.
Lab.
Public
Health
27(
2):
105­
112)

plus
LOAEL=
114
mg/
kg/
day
(
0.2%)
based
on
increased
caecum
weight
and
slight
kidney
damage
in
a
6
month
rat
dietary
study
(
Yoneyama
et
al
1972
Ann.
Rep.
Tokyo
Metrop.
Res.
Lab.
Public
Health
24:
409­
440)

Short­,
intermediateand
Long­
Term
Inhalation
(
1
to
30
days,
1­
6
months,
>
6
months)
Inhalation
study
NOAEL=
1mg/
m3
detergent
dust
combined
with
up
to
0.1
mg/
m3
enzyme
dust
Equivalent
to
approximately
0.14
mg/
kg/
day
(
a)
(
inhalation
absorption
rate
=
100%)
purity=
13%
active
ingredient
Residential
LOC
for
MOE
=
100
Occupational
LOC
for
MOE
=
100
Subchronic
Inhalation
Monkey
Study
LOAEL
=
10
mg/
m3
detergent
combined
with
0.1
mg/
m3
enzyme
dust
based
on
weight
loss
and
decreased
weight
gain
(
W.
Coates,
et
al
1978.
Tox.
Appl.
Pharmacol.
45:
477­
496)
This
air
concentration
is
equivalent
to
approximately
1.4
mg/
kg/
day
(
a)
42
of
42
Table
3.
Summary
of
Toxicological
Dose
and
Endpoints
for
Alkylbenzene
Sulfonates
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
Special
FQPA
SF*,
endpoint
and
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
Dermal
Endpoint
Quantification
of
dermal
risk
is
not
required
since:
1)
the
alkylbenzene
sulfonates
are
surfactants
that
are
dermal
irritants
at
concentrations
generally
greater
than
20%
solution
(
WHO
1996).
Thus,
dermal
exposure
would
be
self­
limiting
to
preclude
dermal
irritation.
Most
pesticide
formulations
have
less
than
5%
alkylbenzene
sulfonates
as
an
inert
ingredient,
with
the
vast
majority
of
household
products
containing
approximately
2%.
Additionally,
the
requirement
of
the
dermal
toxicity
studies
with
the
end­
use
product
will
determine
whether
personal
protective
clothing
would
be
necessary
to
protect
against
irritation
during
product
use;
2)
no
systemic
toxicity
was
seen
following
repeated
dermal
applications
to
rabbits
at
200
mg/
kg/
day
(
with
an
end
use
product);
3)
no
developmental
toxicity
concerns
were
seen
following
repeated
dermal
applications
to
pregnant
mice,
rats
or
rabbits
(
developmental
effects
were
seen
either
in
the
presence
of
maternal
toxicity
or
at
doses
higher
than
those
that
caused
maternal
toxicity);
and
4)
there
is
no
residential
exposure
to
alkylbenzene
sulfonates
as
an
active
ingredient,
however,
residential
exposure
from
its
use
as
an
inert
ingredient
in
pesticide
formulations
is
expected
to
be
of
an
intermittent
nature
(
i.
e,
no
continuous,
constant
contact,
multi­
day
exposure)
from
household
products.

Cancer
(
oral,
dermal,
inhalation)
No
evidence
of
carcinogenicity
in
reported
studies
in
rats
done
before
1980
GLPs
UF
=
uncertainty
factor,
FQPA
SF
=
Special
FQPA
safety
factor,
NOAEL
=
no
observed
adverse
effect
level,
LOAEL
=
lowest
observed
adverse
effect
level,
PAD
=
population
adjusted
dose
(
a
=
acute,
c
=
chronic)
RfD
=
reference
dose,
MOE
=
margin
of
exposure,
LOC
=
level
of
concern,
NA
=
Not
Applicable
NOTE:
No
Special
FQPA
Safety
Factor
recommended
because
it
is
assumed
that
the
exposure
databases
(
dietary
food,
drinking
water,
and
residential)
are
complete
and
that
the
risk
assessment
for
each
potential
exposure
scenario
includes
all
metabolites
and/
or
degradates
of
concern
and
does
not
underestimate
the
potential
risk
for
infants
and
children.
(
a)
Equation
used
to
convert
inhalation
air
concentration
to
a
dose=
mg/
L*
absorption*
respiratory
volume
(
L/
hr)*
duration
(
hrs)
*
activity
factor
/
body
weight.
Thus,
0.001
mg/
L
*
1*
67.94
L/
hr
(
based
on
default
respiratory
volumes
for
a
New
Zealand
Rabbit
which
is
used
as
a
surrogate
for
a
cynomolgus
monkey)
*
6
hrs
*
1
/
2.98
kg
(
body
weight
for
New
Zealand
Rabbit
used
as
a
surrogate
for
cynomolgus
monkey,
study
reports
monkey
body
weight
ranges
from
1.6
to
3.7
kg).