Page
1
of
62
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
Date:
March
23,
2006
MEMORANDUM
SUBJECT:
Alkylbenzene
Sulfonates
(
ABS)
Preliminary
Risk
Assessment
for
the
Reregistration
Eligibility
Decision
(
RED)
Document.
PC
Code:
079010,
190116
and
098002.
Case
No.
4006.
DP
Barcode:
D323972
Regulatory
Action:
Reregistration
Eligibility
Decision
(
RED)
(
Phase
I)
Risk
Assessment
Type:
Single
Chemical
Aggregate
FROM:
Deborah
Smegal,
MPH,
Toxicologist/
Risk
Assessor
Ayaad
Assaad,
PhD.
Toxicologist
William
Dykstra,
PhD.,
Toxicologist
Health
Effects
Division
(
HED)
(
7509C)

And
Talia
Milano,
Chemist
Robert
Quick,
Chemist
Richard
Petrie,
Agronomist
Cassi
Walls,
PhD,
Chemist
Najm
Shamim,
Ph.
D.
Chemist
Antimicrobials
Division
(
AD)
(
7510C)

And
Kerry
Leifer,
Chemist
Registration
Division
(
RD)

THRU:
Phang
Whang,
Branch
Senior
Scientist
Reregistration
Branch
I
Health
Effects
Division
(
HED),
(
7509C)

TO:
Heather
Garvie,
Chemical
Review
Manager,
Reregistration
Team
36
Regulatory
Management
Branch
II
Antimicrobials
Division
(
7510C)
Page
2
of
62
Attached
is
the
Preliminary
Risk
Assessment
for
the
Alkylbenzene
Sulfonates
(
ABS)
for
the
purpose
of
issuing
a
Reregistration
Eligibility
Decision
(
RED).
The
disciplinary
science
chapters
and
other
supporting
documents
for
the
Alkylbenzene
Sulfonates
RED
are
also
included
as
attachments
as
follows:

Occupational
and
Residential
Exposure
Assessment
for
Alkylbenzene
Sulfonates
for
the
Reregistration
Eligibility
Decision
Document
(
RED)
(
Active
Uses).
T.
Milano.
March
23.
D327732
Residential
Exposure
Inert
Assessment
of
Alkylbenzene
Sulfonates
for
the
Reregistration
Eligibility
Decision
Document
(
RED).
T.
Milano/
C.
Walls,
March
23,
2006.
D327733
Environmental
Fate
Assessment
of
Alkylbenzene
Sulfonates
for
the
Reregistration
Eligibility
Document
(
RED).
T.
Milano.
March
23,
2006.
D323968
Product
Chemistry
Science
Chapter
for
Benzene
Sulfonic
Acid,
C10­
C16
Derivatives
and
Sodium
Salt.
A.
N.
Shamim.
March
2006.
D323976.
Ecological
Hazard
and
Environmental
Risk
Assessment
of
Alkylbenzene
Sulfonates
for
the
Registration
Eligibility
Document
(
RED).
R.
Petrie.
January
2006.
D323970.
Dietary
Exposure
Assessments
for
the
Reregistration
Eligibility
Decision.
R.
Quick.
March
23,
2006.
D327731.
Toxicology
Disciplinary
Chapter
for
the
Reregistration
Eligibility
Decision
(
RED)
Document,
A.
Assaad/
W.
Dyksra/
L.
Scarano,
March
23,
2006.
D327886.
Inert
Ingredient
Dietary
Risk
Assessment
for
Linear
Alkyl
Benzenesulfonate.
K.
Leifer.
March
23,
2006.
Page
3
of
62
1.0
EXECUTIVE
SUMMARY......................................................................................................................
4
2.0
PHYSICAL
AND
CHEMICAL
PROPERTIES......................................................................................
12
3.0.
ENVIRONMENTAL
FATE
..................................................................................................................
13
4.0
HAZARD
CHARACTERIZATION.......................................................................................................
14
4.1
Hazard
Profile
.........................................................................................................................
14
4.2
FQPA
Considerations..............................................................................................................
16
4.3
Dose­
Response
Assessment
.....................................................................................................
17
4.4
Endocrine
Disruption.............................................................................................................
19
5.0
PUBLIC
HEALTH
DATA.....................................................................................................................
20
6.0
EXPOSURE
ASSESSMENT
AND
CHARACTERIZATION.................................................................
21
6.1
Summary
of
Registered
Uses
.............................................................................................
21
6.2
Dietary
Exposure
and
Risk................................................................................................
22
6.2.1
Dietary
Exposure
for
Active
Ingredient
Uses
.....................................................................
22
6.2.2
Dietary
Exposure
for
Inert
Ingredient
Uses........................................................................
25
6.3
Drinking
Water
Exposure
and
Risk
for
Inert
Ingredient
Uses
..............................................
26
6.4
Residential
Exposure
and
Risks
from
Inert
Ingredient
Use.................................................
28
7.0
AGGREGATE
RISK
ASSESSMENTS
AND
RISK
CHARACTERIZATION........................................
31
8.0
CUMULATIVE
EXPOSURE
AND
RISK
.............................................................................................
34
9.0
OCCUPATIONAL
EXPOSURE
AND
RISK.........................................................................................
35
10.0
ENVIRONMENTAL
RISK
...................................................................................................................
39
10.1
Active
Ingredient
Uses......................................................................................................
39
10.2
Inert
Ingredient
Use
..........................................................................................................
43
11.0
DEFICIENCIES/
DATA
NEEDS............................................................................................................
43
12.0
REFERENCES......................................................................................................................................
44
Page
4
of
62
1.0
EXECUTIVE
SUMMARY
The
alkylbenzene
sulfonates
evaluated
in
this
risk
assessment
are:
(
1)
sodium
dodecylbenzene
sulfonate
(
CAS
#
25155­
30­
0),
(
2)
dodecylbenzene
sulfonic
acid
(
CAS
#
27176­
87­
0),
and
(
3)
benzenesulfonic
acid,
C10­
C16
alkyl
derivatives
(
CAS
#
68584­
22­
5).
These
compounds
are
collectively
called
DDBSA
by
the
DDBSA
Joint
Venture
Task
Force.
Dodecylbenzene
sulfonic
acid
is
not
considered
to
be
a
pure
compound,
and
is
included
in
the
mixture
of
benzenesulfonic
acid,
C10­
16
alkyl
derivatives.

The
alkylbenzene
sulfonates
are
both
active
and
inert
ingredients
in
pesticide
products.
As
active
ingredients,
there
are
currently
twenty­
three
registered
end­
use
products
used
as
a
disinfectant,
food­
contact
sanitizer,
bacteriocide/
bacteriostat,
microbiocide/
microbiostat,
fungicide/
fungistat,
and
virucide.
Alkylbenzene
sulfonates
are
in
cleaners
and
sanitizers
that
are
designated
for
use
in
agricultural,
food
handling
and
commercial/
institutional/
industrial
settings.
Examples
of
registered
uses
for
alkylbenzene
sulfonates
include,
but
are
not
limited
to:
application
to
indoor
hard
surfaces
(
e.
g.
urinals,
shower
stalls,
toilet
bowls,
etc.),
food
dispensing
equipment
(
e.
g.
pre­
mix
and
post­
mix
vending
machines),
food
contact
surfaces
(
glasses,
dishes,
silverware,
countertops,
etc.),
agricultural
tools,
and
fruits
and
vegetables
(
post­
harvest).
As
active
ingredients,
there
are
no
residential
or
outdoor
uses
currently
registered.
Concentrations
of
alkylbenzene
sulfonates
as
an
active
ingredient
in
products
range
from
0.036%
to
25.6%.
Products
containing
alkylbenzene
sulfonates
are
formulated
as
soluble
concentrates,
flowable
concentrates,
ready­
to­
use
solutions,
or
water
soluble
packaging.

As
inert
ingredients,
there
are
approximately
350
registered
end­
use
products
containing
these
chemicals.
Many
of
these
products
are
used
in
residential
settings,
and
outdoors
in
agricultural
settings.
The
percent
formulations
for
most
of
the
products
that
contain
alkylbenzene
sulfonates
as
an
inert
ingredient
range
from
0.01%
to
5%.
However,
the
majority
of
the
labels
in
this
range
contain
2%
alkylbenzene
sulfonates.
It
should
be
noted
that
a
few
sanitizing
products
have
inert
levels
as
high
as
30%
and
the
highest
concentration
of
alkylbenzene
sulfonates
are
found
in
wood
preservative
products
up
to
65
%.

Of
the
approximate
30
million
pounds
of
alkylbenzene
sulfonates
produced
per
year,
0.1%
or
300,000
pounds
are
used
in
EPA
registered
antimicrobial
products.
The
rest
is
primarily
used
in
household
laundry
and
dish
detergents
annually.
The
alkylbenzene
sulfonates
are
listed
on
the
EPA
High
Production
Volume
(
HPV)
Challenge
Program.
HPV
chemicals
are
those
that
are
manufactured
or
imported
into
the
U.
S.
in
production
volumes
greater
than
one
million
pounds
per
year.
The
alkylbenzene
sulfonates
are
sponsored
by
the
Linear
Alkylbenzene
(
LAB)
Sulfonic
Acids
Coalition,
which
has
generated
data
for
these
chemicals.

Hazard:
The
toxicology
database
for
the
alkylbenzene
sulfonates
consists
almost
entirely
of
published
literature,
and
is
essentially
complete
and
of
acceptable
quality
to
assess
the
potential
hazard
to
humans.
The
alkylbenzene
sulfonates
are
readily
absorbed
following
oral
ingestion,
but
not
following
dermal
exposure.
Following
oral
exposure,
they
are
readily
metabolized,
excreted
fairly
rapidly,
and
do
not
accumulate
in
any
tissues.
Available
acute
toxicity
data
show
that
alkylbenzene
sulfonates
are
not
highly
acutely
toxic
(
Categories
III­
IV),
are
irritating
to
the
eye
and
skin
(
categories
I
and
II,
respectively),
and
they
are
weak­
moderate
skin
sensitizers.
Page
5
of
62
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
alkylbenzene
sulfonates
are
not
genotoxic.
The
alkylbenzene
sulfonates
did
not
cause
reproductive
or
developmental
toxicity
in
acceptable
studies.
Early
(
pre­
GLP)
carcinogenicity
studies
indicate
that
alkylbenzene
sulfonates
do
not
cause
an
increase
in
tumor
incidence.

Toxicity
Endpoints:
The
toxicity
endpoints
used
in
this
document
to
assess
potential
risks
include
chronic
dietary,
short­
term
incidental
oral,
and
short­,
intermediate­
and/
or
long­
term
inhalation
exposure
scenarios.
The
Health
Effects
Division's
Toxicity
Advisory
Clinic
(
TAC)
was
consulted
and
agreed
with
the
choice
of
toxicity
endpoints
of
concern
selected
for
the
aforementioned
exposure
scenarios
in
December
2005
for
the
alkylbenzene
sulfonates
as
a
group.

Acute
and
Chronic
Reference
Dose
(
RfDs):
No
acute
dietary
endpoint
was
selected
because
there
were
no
effects
attributable
to
a
single
dose
exposure.

The
chronic
RfD
is
0.5
mg/
kg/
day
for
all
populations,
using
a
no­
observable
adverse
effect
level
(
NOAEL)
of
50
mg/
kg/
day
based
on
a
weight
of
evidence
from
three
toxicological
studies
that
observed
decreased
pup
body
weight
at
250
mg/
kg/
day
and
increased
caecum
weight
and
slight
kidney
damage
at
114
mg/
kg/
day.
An
uncertainty
factor
of
100
(
10X
for
interspecies
extrapolation,
10X
for
intraspecies
variability)
was
applied
to
the
NOAEL
to
obtain
the
chronic
RfD.

Incidental
oral
Exposure:
For
the
short­
term
incidental
oral
exposure,
a
NOAEL
of
50
mg/
kg/
day
was
selected
based
on
a
weight
of
evidence
from
three
toxicological
studies
that
observed
decreased
pup
body
weight
at
250
mg/
kg/
day
and
increased
caecum
weight
and
slight
kidney
damage
at
114
mg/
kg/
day.
The
target
margin
of
exposure
(
MOE)
is
100
(
10X
for
interspecies
extrapolation,
10X
for
intraspecies
variability,
and
1X
FQPA
factor
discussed
below).

Dermal
Exposure:
The
Agency
determined
that
quantitation
of
dermal
risk
is
not
required
because:
(
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.
Page
6
of
62
Inhalation
Exposure:
For
the
short­,
intermediate­
and
long­
term
inhalation
exposure
a
NOAEL
of
1
mg/
m3
was
selected
(
equivalent
to
0.14
mg/
kg/
day)
from
a
subchronic
inhalation
monkey
study
that
noted
weight
loss
and
decreased
weight
gain
at
10
mg/
m3
(
1.4
mg/
kg/
day)
following
exposure
to
a
detergent
dust
containing
13%
active
ingredient
of
alkylbenzene
sulfonates.
In
the
absence
of
data,
it
was
conservatively
assumed
that
inhalation
absorption
is
100%
to
convert
the
air
concentration
into
a
dose
equivalent.
The
target
MOE
is
100
for
both
residential
and
occupational
exposures
(
10X
for
interspecies
extrapolation,
10X
for
intraspecies
variability,
includes
1X
FQPA
factor
discussed
below).

FQPA
Safety
Factor.
The
TAC
agreed
that
the
FQPA
safety
factor
should
be
removed
(
1X).
A
number
of
developmental
studies
via
the
oral
route
have
been
performed
with
alkylbenzene
sulfonates
in
rats,
mice
and
rabbits.
The
available
information
in
these
studies
does
not
suggest
any
qualitative
or
quantitative
evidence
for
susceptibility
between
the
fetuses
and
maternal
animals.
The
alkylbenzene
sulfonates
were
tested
in
several
multigeneration
studies
in
rats,
and
there
were
no
effects
on
offspring
toxicity
in
any
of
these
tests
at
doses
up
to
250
mg/
kg/
day.

Based
on
OPP
policy,
the
cRfD
modified
by
a
FQPA
safety
factor
is
a
population
adjusted
dose
(
PAD)
1.
OPP
calculated
a
chronic
PAD
and
used
this
value
to
estimate
chronic
dietary
risk.

Dietary
(
Food/
Drinking
Water)
Exposure
and
Risk:
The
Agency
has
conducted
three
chronic
dietary
exposure
and
risk
assessments
for
the
alkylbenzene
sulfonates:
(
1)
as
active
ingredients
in
food
contact
sanitizing
solutions;
(
2)
as
active
ingredients
in
a
fruit
and
vegetable
wash;
and
(
3)
as
inert
ingredients
in
pesticide
formulations
that
may
be
applied
to
growing
agricultural
crops,
raw
agricultural
commodities
after
harvest,
and
to
animals.
An
acute
dietary
assessment
was
not
conducted
because
there
are
no
adverse
effects
attributable
to
a
single
dose.

In
assessing
the
food
contact
sanitizing
uses,
the
Agency
believes
that
a
counter
top,
utensils
or
glassware
that
are
treated
with
these
products
may
come
into
contact
with
food,
which
in
turn
may
be
ingested.
This
is
considered
to
be
an
indirect
food
use.
Dodecylbenzene
sulfonic
acid
(
27176­
87­
0)
and
sodium
dodecylbenzene
sulfonate
(
25155­
30­
0)
have
tolerance
exemptions
as
specified
in
40
CFR
180.940
(
b)
and
(
c).
Both
dodecylbenzene
sulfonic
acid
and
sodium
dodecylbenzene
sulfonate
have
limitations
for
the
ready­
to­
use
end­
use
concentration
not
to
exceed
400
ppm
and
430
ppm,
respectively
for
food
processing
equipment
and
utensils.
However,
dodecylbenzene
sulfonic
acid
has
a
much
lower
limitation
of
5.5
ppm
for
use
on
dairy
processing
equipment.

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

1
PAD
=
Population
Adjusted
Dose
=
Chronic
RfD
FQPA
Safety
Factor
Page
7
of
62
Active
Ingredient
Dietary
Risk
Estimates.
There
are
no
currently
registered
outdoor
uses
of
alkylbenzene
sulfonates
that
are
being
supported
by
the
registrant
as
an
active
ingredient.
Thus,
the
dietary
assessment
for
active
uses
was
limited
to
potential
food
exposures.
The
risk
analysis
assumes
daily
exposure
from
the
hard
surface
sanitation
of
counter
tops,
utensils,
glassware
and
food
processing
equipment
(
i.
e.,
beverage
plants,
meat
and
poultry
processing
plants,
milk
and
dairy
plants).
The
dietary
risk
estimates
for
the
fruit
and
vegetable
wash
were
considered
separately,
because
this
use
is
regulated
by
the
Food
and
Drug
Administration
(
FDA).
The
dietary
risk
estimates
for
the
total
food
contact
sanitizing
uses
are
below
the
Agency's
level
of
concern
for
all
age
groups
(
less
than
11%
of
the
cPAD).
In
addition,
the
dietary
risk
estimates
for
the
fruit
and
vegetable
wash
are
below
the
Agency's
level
of
concern
for
all
age
groups
(
less
than
71.2%
of
the
cPAD).
These
risk
estimates
are
based
on
a
number
of
conservative
assumptions,
and
thus
may
overestimate
the
actual
risks.

Inert
Ingredient
Dietary
Risk
Estimates.
The
alkylbenzene
sulfonates
have
some
uses
as
inert
ingredients
in
food­
use
pesticide
products
that
are
used
outdoors
on
agricultural
crops.
Thus,
the
inert
assessment
considered
both
food
and
drinking
water
exposures.
The
Agency
utilized
a
conservative
screening
level
dietary
exposure
model
[
Dietary
Exposure
Evaluation
Model
(
DEEM
 
)
]
that
assumed
100%
of
all
commodities,
and
100%
of
all
crops
were
treated
with
the
alkylbenzene
sulfonates,
with
no
limitation
on
the
fraction
of
inert
ingredient.
The
highest
dietary
risk
estimate
is
84%
of
the
cPAD
for
children
1­
2
years
of
age,
which
is
below
the
Agency's
level
of
concern.
The
conservative
screening­
level
drinking
water
assessment
predicted
chronic
Estimated
Drinking
Water
Concentrations
(
EDWC)
of
6.6
ppb
using
the
FQPA
Index
Reservoir
Screening
Tool
(
FIRST),
which
represents
<
0.1%
of
the
cPAD.
The
Agency
concludes
there
is
no
concern
for
aggregate
food
and
drinking
water
exposures
to
the
alkylbenzene
sulfonates
resulting
from
their
use
as
pesticide
inert
ingredients.

Residential
(
Non­
Occupational)
Exposure
and
Risk:
There
are
no
residential
use
sites
for
the
alkylbenzene
sulfonates
as
active
ingredients.
However,
alkylbenzene
sulfonates
are
formulated
as
inert
ingredients
in
approximately
350
registered
end­
use
products,
many
of
which
are
used
in
residential
settings.
Some
examples
of
the
specified
use
sites
on
the
products
consist
of
indoor
hard
non­
porous
surfaces
(
e.
g.
floors,
walls
etc.),
carpets,
food
contact
surfaces
(
glasses,
dishes,
silverware,
countertops,
etc.),
agricultural
tools
and
crops,
lawns
and
turfs,
fruits
and
vegetables
(
post­
harvest),
wood
preservatives,
materials
preservatives,
metalworking
fluids,
and
pet
products.
In
this
screening
level
assessment,
the
Agency
selected
representative
scenarios
for
the
vast
majority
of
products,
based
on
end­
use
product
application
methods
and
use
amounts.
The
Agency
evaluated
the
following
high
end
exposure
scenarios:
(
1)
outdoor
residential
turf
treatment
(
ready
to
use
liquid);
(
2)
indoor
hard
surface
cleaner
(
ready
to
use
liquid);
(
3)
indoor
carpet
cleaner
(
ready
to
use
liquid);
and
(
4)
pet
flea
and
tick
products
(
aerosol
can
spray).
For
each
of
the
use
sites,
the
Agency
assessed
residential
handler
(
applicator)
inhalation
exposure
and
post
application
incidental
ingestion
by
toddlers.
Page
8
of
62
For
most
scenarios,
the
Agency
utilized
EPA's
Pesticide
Inert
Risk
Assessment
Tool
(
PiRat)
to
estimate
residential
applicator
and
post­
application
exposures
from
the
use
of
alkylbenzene
sulfonates
as
inert
ingredients
in
residential
products.
For
the
pet
product
scenario,
the
Agency
used
assumptions
based
on
the
Residential
Exposure
Assessment
Standard
Operating
Procedures
(
SOPs).
Because
there
are
a
large
number
of
products
that
contain
alkylbenzene
sulfonates
as
an
inert
ingredient,
the
Agency
assessed
both
a
high
end
formulation
in
addition
to
a
2%
formulation
product.
The
2%
value
was
selected
because
the
majority
of
the
labels
contain
2%
alkylbenzene
sulfonates
as
an
inert
ingredient.
A
dermal
assessment
was
not
conducted
because
a
dermal
endpoint
was
not
selected.
An
inhalation
post­
application
assessment
was
not
conducted
because
the
vapor
pressure
of
the
sulfonates
is
extremely
low.
The
duration
of
exposure
was
assumed
to
be
short­
term
(
1­
30
days)
for
all
residential
scenarios
assessed.

Residential
Handler
Risk
Estimates.
For
residential
handlers
that
handle
products
containing
alkylbenzene
sulfonates
as
inert
ingredients,
the
short­
term
inhalation
MOEs
were
above
the
target
MOEs
(
i.
e.,
 
>
100)
and
thus,
do
not
exceed
the
Agency's
level
of
concern,
with
the
exception
of
the
flea
and
tick
product
where
the
MOE
was
87
for
the
high­
end
formulation
containing
24%
alkylbenzene
sulfonates.
T.
However,
this
scenario
is
conservative
because
it
assumes
a
person
treats
his/
her
pet
with
0.5
cans
of
flea
product
that
contains
24%
alkylbenzene
sulfonates
every
day
for
a
month.
However,
there
are
no
risk
concerns
for
the
majority
of
pet
products
containing
2%
alkylbenzene
sulfonates.

Residential
Postapplication
Risk
Estimates.
There
are
no
residential
postapplication
risk
concerns
for
the
majority
of
household
products
that
contain
2%
alkylbenzene
sulfonates
as
an
inert
ingredient.
However,
there
are
potential
postapplication
incidental
oral
risks
to
young
children
resulting
from
indoor
use
of
products
that
may
contain
alkylbenzene
sulfonates.
The
MOEs
are
30
and
40
for
hard
surface
and
carpet
cleaners,
respectively,
which
are
less
than
the
Agency's
target
MOE
of
100.
However,
these
risk
estimates
are
considered
to
be
conservative
screening­
level
values,
based
on
products
that
contain
between
6­
8%
alkylbenzene
sulfonates.
The
majority
of
products
contain
concentrations
below
5%.
The
postapplication
incidental
oral
risks
to
children
that
may
contact
a
treated
pet
are
not
of
concern
as
the
range
of
MOEs
(
106­
1,300)
is
above
the
target
MOE
of
100.

The
alkylbenzene
sulfonates
caused
dermal
irritation
following
repeated
dermal
exposure,
generally
to
concentrations
greater
than
20%.
Thus,
dermal
exposure
would
be
self­
limiting
to
preclude
dermal
irritation.
The
majority
of
residential
products
contain
less
than
5%
akylbenzene
sulfonates.
The
Agency
intends
to
consider
the
potential
for
irritation
in
recommended
labeling
language
of
pesticide
products
containing
the
alkylbenzene
sulfonates,
and
consider
available
dermal
toxicity
data
on
a
diluted
end­
use
formulation.

Aggregate
Exposure
and
Risk:
In
order
for
a
pesticide
registration
to
continue,
it
must
be
shown
that
the
use
does
not
result
in
"
unreasonable
adverse
effects
on
the
environment".
Section
2
(
bb)
of
FIFRA
defines
this
term
to
include
"
a
human
dietary
risk
from
residues
that
result
from
a
use
of
a
pesticide
in
or
on
any
food
inconsistent
with
standard
under
section
408..."
of
FFDCA.
As
mandated
by
the
FQPA
amendments
to
FIFRA
and
the
Federal
Food,
Drug
and
Cosmetic
Act
(
FFDCA),
the
Agency
must
consider
total
aggregate
exposure
from
food,
drinking
water
and
residential
sources
of
exposure
to
alkylbenzene
sulfonates.
Page
9
of
62
An
acute
aggregate
assessment
was
not
conducted
because
there
are
no
adverse
effects
attributable
to
acute
exposure.
An
intermediate­
term
aggregate
assessment
was
not
conducted
because
there
are
no
residential
exposures
of
this
duration.
In
addition,
because
there
are
no
long­
term
residential
exposures,
the
chronic
aggregate
assessment
only
considered
food
and
drinking
water
exposures
from
the
inert
uses
that
were
previously
determined
to
not
be
of
risk
concern.
Thus,
only
short­
term
and
chronic
aggregate
assessments
were
conducted.
Oral
and
inhalation
exposure
and
risk
estimates
were
conservatively
combined
for
the
aggregate
risk
assessment
because
these
endpoints
both
identify
adverse
effects
on
body
weight.
Dermal
exposures
were
not
considered
in
the
risk
assessment
because
a
toxicological
endpoint
was
not
established.

Short­
Term.
This
assessment
considers
both
the
active
and
inert
uses
of
the
alkylbenzene
sulfonates.
For
children,
the
short­
term
aggregate
assessment
includes
average
dietary
exposure
(
food
and
drinking
water)
from
both
the
active
food
contact
sanitizer
uses
and
the
inert
uses
on
agricultural
commodities,
in
addition
to
estimated
incidental
oral
exposures
to
children
from
residential
uses
such
as
hard
surface
cleaning
products
as
an
inert
ingredient.
For
adults,
the
aggregate
assessment
includes
dietary
(
food
and
drinking
water)
from
both
active
and
inert
uses
and
residential
inhalation
exposures
from
wiping
a
hard
surface
cleaning
products
since
this
scenario
represents
the
highest
exposure
from
the
inert
use.
Individual
scenarios
that
had
risks
of
concern
were
not
included
in
the
aggregate
assessment.

The
aggregate
oral
and
inhalation
risks
are
not
of
concern
for
adults,
as
the
total
aggregate
MOE
is
340
which
is
greater
than
the
target
of
100.
For
children,
the
aggregate
risk
estimates
are
less
than
the
target
MOE
of
100
(
MOE=
54)
and
are
of
risk
concern.
The
aggregate
child
risks
are
of
concern
because
both
the
dietary
and
residential
scenarios
alone
are
very
close
to
the
target
MOEs
or
100%
of
the
cPAD
(
i.
e.,
food
and
drinking
water
accounts
for
approximately
95%
of
the
cPAD),
while
the
incidental
oral
exposure
from
a
hard
surface
cleaner
MOE
is
120
(
for
a
2%
product).
As
noted
previously,
several
conservative
assumptions
were
used
in
this
assessment.

Chronic
Aggregate.
The
chronic
aggregate
assessment
considers
average
dietary
exposure
(
food
and
drinking
water)
from
both
the
active
food
contact
sanitizer
uses
and
the
inert
uses
on
agricultural
commodities.
The
dietary
exposures
from
the
fruit
and
vegetable
wash
were
not
considered
because
they
already
exceed
the
Agency's
level
of
concern.
For
children,
the
dietary
aggregate
risk
is
95%
of
the
cPAD,
while
for
adults
it
is
29%
of
the
cPAD.

It
should
also
be
recognized
that
the
majority
of
the
uses
of
alkylbenzene
sulfonates
are
not
in
pesticide
products,
but
rather
are
used
in
household
laundry
and
dish
detergents.
Over
30
millions
pounds
of
these
compounds
are
produced
each
year,
while
only
300,000
pounds
are
used
in
EPA
registered
antimicrobial
products.
The
Agency
did
not
consider
potential
exposure
and
risks
from
the
numerous
other
residential
exposures
to
alkylbenzene
sulfonates
because
the
Agency
lacks
reliable
information
at
this
time
to
assess
the
consumer
product
uses
of
these
chemicals.

Occupational
Exposure
and
Risk.
Based
on
examination
of
product
labels
describing
uses
for
the
product,
it
has
been
determined
that
exposure
to
handlers
can
occur
in
a
variety
of
Page
10
of
62
occupational
environments.
The
representative
scenarios
selected
by
the
Agency
for
assessment
were
evaluated
using
maximum
application
rates
as
recommended
on
the
product
labels
for
the
three
alkylbenzene
sulfonate
active
ingredients
assessed
in
this
report.

To
assess
the
handler
risks,
the
Agency
used
surrogate
unit
exposure
data
from
both
the
proprietary
Chemical
Manufacturers
Association
(
CMA)
antimicrobial
exposure
study
and
the
Pesticide
Handlers
Exposure
Database
(
PHED).
Only
inhalation
risks
were
evaluated
because
a
dermal
toxicity
endpoint
was
not
selected.
For
the
occupational
handler
inhalation
risk
assessment,
the
short­
and
intermediate­
term
risks
calculated
at
baseline
exposure
(
no
respirators)
were
above
target
MOEs
for
all
scenarios
(
i.
e.,
inhalation
MOEs
were
>
100)
for
all
scenarios
except
the
following:

 
ST
and
IT
inhalation
exposure
from
cleaning
hard
surfaces
via
circulation/
flow/
flushing
in
the
agricultural
premises
and
equipment
category,
inhalation
MOE
<
1.
 
ST
and
IT
inhalation
exposure
from
application
to
hard
surfaces
via
(
1)
circulation
systems/
flow
method,
or
(
2)
Cleaning
in
Place
(
CIP)
in
the
food
handling
category,
inhalation
MOE
<
1.
 
ST
and
IT
inhalation
exposure
from
cleaning
hard
surfaces
via
wiping
in
the
food
handling
category,
inhalation
MOE
=
93.
 
ST
and
IT
inhalation
exposure
from
cleaning
food
dispensing
equipment
via
circulation
systems/
flow
method
in
the
food
handling
category,
inhalation
MOE
<
1.
 
ST
and
IT
Inhalation
exposure
from
cleaning
shower
stalls
and
toilets
via
(
1)
a
liquid
pour
application
or
(
2)
wiping
in
the
commercial/
institutional
premises,
inhalation
MOE
=
13
and
MOE
<
1,
respectively.

Many
product
labels
have
use
directions
that
recommend
both
cleaning
and
sanitizing
with
the
same
product.
Thus,
the
Agency
estimated
total
risks
resulting
from
use
of
these
specific
products.
The
following
scenarios
had
risks
of
concern
(
i.
e.,
MOE
<
100).

 
ST
and
IT
inhalation
exposure
from
cleaning
indoor
hard
surfaces
via
wiping
and
then
following
with
sanitizing
via
immersion/
flooding
in
the
food
handling
premises
category,
inhalation
MOE
=
93.
 
ST
and
IT
inhalation
exposure
from
cleaning
indoor
hard
surfaces
via
wiping
and
then
following
with
sanitizing
via
low
pressure
spray
in
the
food
handling
premises
category,
inhalation
MOE
=
90.
 
ST
and
IT
inhalation
exposure
from
cleaning
indoor
hard
surfaces
via
sponge/
mesh/
wiping
and
then
sanitizing
via
immersion/
flooding
in
the
food
handling
premises
category,
inhalation
MOE
=
90.
 
ST
and
IT
inhalation
exposure
from
cleaning
and
sanitizing
steps
to
be
conducted
through
CIP
(
Cleaning
in
Place)
in
the
food
handling
premises
category,
inhalation
MOE
<
1.

Although
all
the
inhalation
risks
of
concern
are
for
baseline
exposures,
the
Agency
does
not
believe
it
is
practicable
to
require
the
use
of
respiratory
protection
on
cleaning
products
used
in
janitorial
situations.
In
addition,
engineering
controls
are
not
feasible
for
the
current
use
patterns
on
the
labels.
Page
11
of
62
As
noted
previously,
the
alkylbenzene
sulfonates
are
dermal
irritants
at
concentrations
greater
than
20%.
Thus,
dermal
exposure
would
be
self­
limiting
to
preclude
dermal
irritation.
The
Agency
intends
to
consider
the
potential
for
irritation
in
recommended
labeling
language
of
pesticide
products
containing
the
alkylbenzene
sulfonates,
and
consider
available
dermal
toxicity
data
on
a
diluted
end­
use
formulation.
The
Agency
should
confirm
that
all
products
with
greater
than
20%
require
the
use
of
gloves.

For
most
of
the
occupational
scenarios,
postapplication
dermal
exposure
is
not
expected
to
occur
or
is
expected
to
be
negligible
based
on
the
application
rates
and
chemical
properties
of
the
chemical.
The
alkylbenzene
sulfonates
have
a
low
vapor
pressure
(
less
than
10­
9
mmHg),
so
that
any
standing
solutions
that
may
result
in
post
application
exposure
were
deemed
negligible.

Environmental
Hazard
and
Risk.
The
alkylbenzene
sulfonates
are
slightly
toxic
to
the
Northern
bobwhite
quail,
and
moderately
toxic
to
freshwater
fish
following
acute
exposure.
Available
data
suggest
that
the
alkylbenzene
sulfonates
may
be
more
toxic
to
aquatic
organisms
as
the
number
of
carbons
in
the
chain
increase.
No
acute
fish
toxicity
data
are
available
for
carbon
chains
above
12,
and
thus
a
fish
environmental
hazard
label
statement
is
required
on
manufacturing
use
product
labels
at
this
time.
The
acute
toxicity
to
the
freshwater
invertebrate,
Daphnia
magna
is
variable,
dependent
on
the
length
of
the
carbon
chain,
and
ranges
from
slightly
to
highly
toxic
to
freshwater
invertebrates.
Based
on
the
available
information,
an
environmental
hazard
statement
for
aquatic
invertebrates
is
required
on
manufacturing
use
products
because
the
EC50
is
<
1.0
ppm
(
C14,
C16).
The
available
data
indicate
that
the
alkylbenzene
sulfonates
are
slightly
toxic
to
green
algae.

The
guideline
requirement
for
a
freshwater
fish
acute
test
(
850.1075),
and
acute
freshwater
invertebrate
study
(
850.1010)
are
outstanding.
These
studies
are
required
to
support
the
current
indoor
uses
and
to
document
potential
acute
toxicity
to
these
organisms
in
the
unlikely
event
that
exposure
to
alkylbenzene
sulfonates
does
occur.

Available
literature
for
linear
alkylbenzene
sulfonate
(
LAS)
detergent
use
indicates
that
the
alkylbenzene
sulfonates
are
not
expected
to
bioaccumulate
in
the
environment
or
aquatic
organisms
(
i.
e.
fish)
and
are
expected
to
be
soluble
in
water
such
that
they
will
exhibit
mobility
through
the
soil.
The
model­
calculated
linear
and
non­
linear
biodegradation
probabilities
suggest
that
these
chemicals
will
most
likely
biodegrade
rapidly.
The
short
half
life
indicates
that
if
these
chemicals
are
present
in
the
soil,
they
are
not
likely
to
be
volatile
and
are
expected
to
degrade
rapidly
in
the
environment.

Minimal
or
no
environmental
exposure
is
expected
to
occur
from
the
majority
of
alkylbenzene
sulfonate
antimicrobial
pesticide
uses
because
a
very
small
number
of
pounds
of
this
chemical
are
sold
for
antimicrobial
use
per
data
provided
by
the
manufacturers.

The
inert
agricultural
uses
of
alkylbenzene
sulfonates
are
not
expected
to
adversely
affect
avian
or
mammalian
species
on
an
acute
or
chronic
basis.
Aquatic
organisms
are
also
not
expected
to
be
adversely
affected
by
inert
alkylbenzene
sulfonates
use
acutely
or
chronically
due
to
the
low
predicted
level
of
alkylbenzene
sulfonates
in
water.
A
chronic
freshwater
fish
toxicity
test
Page
12
of
62
NOAEC
of
400
ug/
L
alkylbenzene
sulfonates
is
considered
protective
of
ecosystem
structure
and
function
in
experimental
streams.
Therefore,
the
predicted
concentration
of
6.6
ppb
in
water
is
well
below
the
Agency's
chronic
Level
of
Concern
(
LOC).

Use
of
alkylbenzene
sulfonates
in
agricultural
pesticide
formulations
is
not
expected
to
result
in
significant
environmental
exposure.
Therefore,
no
adverse
effects
(
NE)
to
listed
species
are
anticipated.

2.0
PHYSICAL
AND
CHEMICAL
PROPERTIES
The
physical
and
chemical
properties
for
the
three
alkylbenzene
sulfonates
assessed
in
this
document:
(
1)
sodium
dodecylbenzene
sulfonate,
(
2)
benzene
sulfonic
acid,
C10­
16­
alkyl
derivatives,
and
(
3)
dodecylbenzene
sulfonic
acid
are
provided
in
Table
1.
The
product
chemistry
chapter
(
memo
from
N.
Shamim,
March
2006,
D323976)
provides
a
comprehensive
list
of
the
different
physical/
chemical
properties.
Below
are
the
chemical
structures.

Figure
1:
Sodium
Dodecylbenzene
Sulfonate
Figure
2:
Dodecylbenzene
Sulfonic
Acid
(
DDBSA)
also
(
also
named
as
dodecylbenzene
sulfonic
representative
of
Benzene
Sulfonic
Acid,
C10
acid,
sodium
salt)
16­
alkyl
derivatives
Table
1
Physical/
Chemical
Properties
of
Linear
Alkylbenzene
Sulfonates
Parameter
Sodium
Dodecylbenzene
Sulfonate
Benzene
Sulfonic
Acid,
C10­
16­
alkyl
derivatives
Dodecylbenzene
Sulfonic
Acid
(
DDBSA)

PC
Chemical
Code
079010
190116
098002
Cas
Number
25155­
30­
0
68584­
22­
5
27176­
87­
0
Molecular
Formula
C18H29O3S
Na
C16H26O3S
C18H30O3S
Page
13
of
62
Table
1
Physical/
Chemical
Properties
of
Linear
Alkylbenzene
Sulfonates
Synonyms
Alkyl(
C12)
benzenesulfonic
acid,
sodium
salt
Benzenesulfonic
acid,
dodecyl­,
sodium
salt
Dodecylbenzene
sodium
sulfonate
Dodecylbenzenesulfonic
acid,
sodium
salt
Sodium
laurylbenzenesulfonate
Benzenesulfonic
acid,
dodecyl
Molecular
Weight
348.48
g/
mol
298.44
g/
mol
326.50
g/
mol
Henry
Law
Constant
6.02
x
10­
17
atm.­
m3/
mol
2.8
x
10­
11
atm­
m3/
mol
4.8
x
10­
11
atm­
m3/
mol
Melting
Point
287.6OC
167.7
OC
178
OC
Boiling
Point
660OC
437
OC
460
OC
Water
Solubility
Highly
water
soluble
400
g/
L
(
25
O
C)
0.7
mg/
L
log
Kow
1.96
3.80
4.78
Vapor
Pressure
6.02
x
10­
15
mm
Hg
5.1
x
10­
10
mm
Hg
(
25o
C)
7.9
x
10­
11
mm
Hg
(
25o
C)

Half­
life
in
air
0.66
days
=
7.9
hours
0.79
days
=
9.48
hours
0.654
days
=
7.85
hours
3.0.
ENVIRONMENTAL
FATE
Detailed
information
on
environmental
fate
is
presented
in
the
attached
memo
from
T.
Milano
(
March
23,
2006,
D323968).
A
brief
summary
is
provided
below.

The
environmental
fate
properties
of
dodecylbenzene
sulfonic
acid
are
assumed
to
be
represented
by
the
conclusions
made
pertaining
to
benzenesulfonic
acid,
C10­
C16
alkyl
derivatives.
This
is
because
dodecylbenzene
sulfonic
acid
(
DDBSA)
is
not
considered
to
be
a
pure
compound,
and
is
actually
included
in
the
mixture
of
benzenesulfonic
acid,
C10­
16
alkyl
derivatives.
These
compounds
will
be
addressed
as
a
group,
DDBSA.

The
environmental
fate
assessment
for
DDBSA
is
based
on
US
EPA
=

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

Based
on
the
output
of
the
model,
sodium
dodecylbenzene
sulfonate
is
highly
unlikely
to
bioaccumulate
in
the
environment
or
aquatic
organisms
(
i.
e.
fish)
because
the
low
value
for
the
log
Kow
(
1.96).
This
also
supports
that
the
chemical
is
soluble
in
water
such
that
it
will
exhibit
mobility
through
the
soil.
In
addition,
the
low
log
Koc
(
4.22)
further
supports
the
expected
soil
mobility.
The
model­
calculated
linear
and
non­
linear
biodegradation
probabilities
suggest
that
the
linear
carbon
chain
will
biodegrade
rapidly,
whereas
the
benzene
ring
is
not
expected
to
biodegrade
as
rapidly.
The
extremely
low
vapor
pressure
along
with
the
short
half
life
of
approximately
7.9
hours
indicates
that
if
this
chemical
is
present
in
the
soil,
it
is
not
likely
to
be
volatile
and
is
expected
to
degrade
rapidly.
Page
14
of
62
Based
on
the
output
of
the
model,
DDBSA
is
expected
to
behave
very
similarly
as
what
is
projected
for
sodium
dodecylbenzene
sulfonate.
Based
on
the
low
Kow
value
(
3.8),
DDBSA
is
highly
unlikely
to
bioaccumulate
in
the
environment
or
aquatic
organisms
(
i.
e.
fish).
The
chemical
is
also
expected
to
be
soluble
in
water
such
that
it
will
exhibit
mobility
through
the
soil.
In
addition,
the
log
Koc
(
3.69)
is
low,
and
this
further
supports
the
expected
soil
mobility.
The
model­
calculated
linear
and
non­
linear
biodegradation
probabilities
suggest
that
the
chemical
will
most
likely
biodegrade
rapidly.
The
extremely
low
vapor
pressure
along
with
the
short
half
life
of
approximately
9.48
hours
indicates
that
this
chemical
is
not
likely
to
be
volatile
and
is
expected
to
degrade
rapidly.

The
output
parameters
from
the
EPI
Suite
model
support
that
any
potential
impacts
of
these
chemicals
are
expected
to
be
very
short­
lived.
This
is
because
they
are
not
likely
to
persist
in
water
or
microbial
soils
and
sediments.
As
a
result,
the
environmental
fate
of
alkylbenzene
sulfonate
is
not
likely
to
be
of
concern.

4.0
HAZARD
CHARACTERIZATION
4.1
Hazard
Profile
The
toxicology
database
for
the
alkylbenzene
sulfonates
consists
almost
entirely
of
published
literature,
is
essentially
complete
and
of
acceptable
quality
to
assess
the
potential
hazard
to
humans.

A
detailed
Toxicology
Assessment
for
the
linear
alkylbenzene
sulfonates
is
presented
in
the
attached
memorandum
(
memo
from
A.
Assaad/
W.
Dykstra/
L.
Scarano,
March
2006).
Table
2
highlights
the
acute
toxicity
studies
for
the
alkylbenzene
sulfonates.
A
detailed
summary
of
the
key
toxicological
studies
is
presented
in
Appendix
A
because
of
the
large
number
of
available
toxicological
information
on
these
compounds.
A
brief
hazard
assessment
is
presented
below.

Acute
Toxicity.
Alkylbenzene
sulfonates
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.
Alkylbenzene
sulfonates
are
classified
as
acute
toxicity
category
II
for
the
dermal
route
and
category
IV
(
least
toxic)
via
the
inhalation
route.
They
are
irritants
to
the
eye
(
category
I),
skin
(
category
II),
and
are
weak­
moderate
skin
sensitizers
(
category
III).

Absorption,
Distribution,
Metabolism,
Excretion.
In
animal
tests
(
oral
 
monkeys,
pigs,
rats),
alkylbenzene
sulfonates
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
alkylbenzene
sulfonates
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).

Repeated
Dose
Toxicity
(
Subchronic
and
Chronic).
There
have
been
many
oral
repeated
dose
studies
performed
with
alkylbenzene
sulfonates
ranging
from
a
28­
day
study
in
monkeys
to
nine
month
studies
conducted
with
rats
and
mice.
There
have
also
been
repeated
dose
dermal
Page
15
of
62
(
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
alkylbenzene
sulfonates
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
alkylbenzene
sulfonates
used
(
some
used
formulated
products
that
ranged
from
1­
45%
alkylbenzene
sulfonates
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
fetuses
and
maternal
animals.

Reproductive
Toxicity.
Alkylbenzene
sulfonates
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
duration
of
dosing,
and
limited
histopathological
examinations.
However,
the
limited
studies
provide
no
evidence
of
carcinogenicity
in
animals
given
alkylbenzene
sulfonates
orally.

Genotoxicity.
The
toxicological
data
show
that
alkylbenzene
sulfonates
were
not
genotoxic
in
vitro
or
in
vivo.

Neurotoxicity.
There
is
no
evidence
in
the
available
toxicity
studies
or
scientific
literate
to
indicate
neurotoxic
effects
of
the
alkylbenzene
sulfonates
in
humans
or
laboratory
animals.

Table
2
Acute
Toxicity
Studies
for
Alkylbenzene
Sulfonates
Guideline
No./
Study
Type
MRID
No.
Results
Toxicity
Category
Page
16
of
62
Table
2
Acute
Toxicity
Studies
for
Alkylbenzene
Sulfonates
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
*
Toxicity
record
No.

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

The
toxicology
database
is
complete
with
respect
to
assessing
the
increased
susceptibility
to
infants
and
children
as
required
by
FQPA
for
alkylbenzene
sulfonates.
The
prenatal
developmental
and
reproduction
studies
showed
no
qualitative
or
quantitative
evidence
of
increased
susceptibility
(
i.
e.,
developmental
NOAELs/
LOAELs
were
the
higher
than
those
for
maternal
effects).
Therefore,
the
FQPA
factor
was
reduced
to
1X.

Several
reproduction
and
many
developmental
studies
have
been
performed
with
alkylbenzene
sulfonate
in
a
number
of
animal
species.
In
the
developmental
studies,
whenever
Page
17
of
62
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
parents
or
offspring
in
the
other
two
reproductive
toxicity
studies
(
see
Toxicity
Profile
Table)
 
high
doses
of
70
or
170
mg/
kg/
day.

There
is
no
evidence
in
the
available
toxicity
studies
or
scientific
literature
to
indicate
neurotoxic
effects
of
the
alkylbenzene
sulfonates
in
humans
or
laboratory
animals.

Based
on
hazard
data,
the
Agency
recommended
the
special
FQPA
SF
be
reduced
to
1X
because
there
are
no
concerns
and
no
residual
uncertainties
with
regard
to
pre­
and/
or
postnatal
toxicity.
The
risk
assessment
team
evaluated
the
quality
of
the
exposure
data;
and
based
on
these
data
the
team
also
recommended
that
the
special
FQPA
SF
be
reduced
to
1X.
There
is
no
need
for
a
special
FQPA
factor
because
the
mid­
dose
level
of
50
mg/
kg/
day
(
NOAEL
for
offspring
effects)
in
a
reproduction
study
(
Buehler
et
al.
1971)
is
the
basis
for
the
chronic
RfD
of
0.5
mg/
kg/
day.
Thus,
the
chronic
hazard
value
is
based
on
slight
pup
effects
and
is
protective
of
laboratory
animals
of
all
ages
in
this
hazard
assessment.

4.3
Dose­
Response
Assessment
The
Health
Effects
Division's
Toxicity
Advisory
Clinic
(
TAC)
was
consulted
and
agreed
with
the
choice
of
toxicity
endpoints
of
concern
in
December
2005
for
the
alkylbenzene
sulfonates
as
a
group.

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.
Page
18
of
62
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
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)

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)
Page
19
of
62
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,
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)

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
(
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).

4.4
Endocrine
Disruption
EPA
is
required
under
the
FFDCA,
as
amended
by
FQPA,
to
develop
a
screening
program
Page
20
of
62
to
determine
whether
certain
substances
(
including
all
pesticide
active
and
other
ingredients)
"
may
have
an
effect
in
humans
that
is
similar
to
an
effect
produced
by
a
naturally
occurring
estrogen,
or
other
such
endocrine
effects
as
the
Administrator
may
designate."
Following
recommendations
of
its
Endocrine
Disruptor
and
Testing
Advisory
Committee
(
EDSTAC),
EPA
determined
that
there
was
a
scientific
basis
for
including,
as
part
of
the
program,
the
androgen
and
thyroid
hormone
systems,
in
addition
to
the
estrogen
hormone
system.
EPA
also
adopted
EDSTAC's
recommendation
that
the
Program
include
evaluations
of
potential
effects
in
wildlife.
For
pesticide
chemicals,
EPA
will
use
FIFRA
and,
to
the
extent
that
effects
in
wildlife
may
help
determine
whether
a
substance
may
have
an
effect
in
humans,
FFDCA
authority
to
require
the
wildlife
evaluations.
As
the
science
develops
and
resources
allow,
screening
of
additional
hormone
systems
may
be
added
to
the
Endocrine
Disruptor
Screening
Program
(
EDSP).

In
the
available
toxicity
studies
on
the
alkylbenzene
sulfonates,
there
was
no
estrogen,
androgen,
and/
or
thyroid
mediated
toxicity.
When
additional
appropriate
screening
and/
or
testing
protocols
being
considered
under
the
Agency's
EDSP
have
been
developed,
alkylbenzene
sulfonates
may
be
subjected
to
further
screening
and/
or
testing
to
better
characterize
effects
related
to
endocrine
disruption.

5.0
PUBLIC
HEALTH
DATA
Incident
Reports.
There
are
no
human
incident
reports
associated
with
alkylbenzene
sulfonates.
The
Agency
consulted
the
following
databases
for
poisoning
incident
data
for
alkylbenzene
sulfonates:

(
1)
OPP
Incident
Data
System
(
IDS)
­
The
Incident
Data
System
of
The
Office
of
Pesticide
Programs
(
OPP)
of
the
Environmental
Protection
Agency
(
EPA)
contains
reports
of
incidents
from
various
sources,
including
registrants,
other
federal
and
state
health
and
environmental
agencies
and
individual
consumers,
submitted
to
OPP
since
1992.
Reports
submitted
to
the
Incident
Data
System
represent
anecdotal
reports
or
allegations
only,
unless
otherwise
stated.
Typically
no
conclusions
can
be
drawn
implicating
the
pesticide
as
a
cause
of
any
of
the
reported
health
effects.
Nevertheless,
sometimes
with
enough
cases
and/
or
enough
documentation
risk
mitigation
measures
may
be
suggested.
(
2)
Poison
Control
Centers
(
1993­
2003)
­
as
the
result
of
a
data
purchase
by
EPA,
OPP
received
Poison
Control
Center
data
covering
the
years
1993
through
2003
for
all
pesticides.
Most
of
the
national
Poison
Control
Centers
(
PCCs)
participate
in
a
national
data
collection
system,
the
Toxic
Exposure
Surveillance
System,
which
obtains
data
from
about
65­
70
centers
at
hospitals
and
universities.
PCCs
provide
telephone
consultation
for
individuals
and
health
care
providers
on
suspected
poisonings,
involving
drugs,
household
products,
pesticides,
etc.
(
3)
California
Department
of
Pesticide
Regulation
(
1982­
2004)
­
California
has
collected
uniform
data
on
suspected
pesticide
poisonings
since
1982.
Physicians
are
required,
by
statute,
to
report
to
their
local
health
officer
all
occurrences
of
illness
suspected
of
being
related
to
exposure
to
pesticides.
The
majority
of
the
incidents
involve
workers.
Information
on
exposure
(
worker
activity),
type
of
illness
(
systemic,
eye,
skin,
eye/
skin
and
respiratory),
likelihood
of
a
causal
relationship,
and
number
of
Page
21
of
62
days
off
work
and
in
the
hospital
are
provided.
(
4)
National
Pesticide
Telecommunications
Network
(
NPTN)
­
NPTN
is
a
toll­
free
information
service
supported
by
OPP.
A
ranking
of
the
top
200
active
ingredients
for
which
telephone
calls
were
received
during
calendar
years
1984­
1991,
inclusive,
has
been
prepared.
The
total
number
of
calls
was
tabulated
for
the
categories
human
incidents,
animal
incidents,
calls
for
information,
and
others.

6.0
EXPOSURE
ASSESSMENT
AND
CHARACTERIZATION
Dietary
exposure
to
alkylbenzene
sulfonates
can
occur
from
its
use
in
food
contact
sanitizing
solutions
as
an
active
ingredient,
and
as
an
inert
ingredient
in
food­
use
pesticide
products
applied
to
agricultural
crops,
and
animals.
There
are
no
currently
registered
products
used
in
residential
settings
where
alkylbenzene
sulfonates
are
considered
to
be
an
active
ingredient.
However,
alkylbenzene
sulfonates
are
used
as
an
inert
ingredient
in
pesticide
products
used
in
residential
settings,
including
hard
surface
and
carpet
cleaners,
lawn
products,
and
pet
products.
Postapplication
residential
exposure
can
occur
in
children
from
hand­
to­
mouth
incidental
oral
exposure
from
treated
surfaces,
and
contacting
pets
treated
with
flea
and
tick
products.
Occupational
exposure
to
alkylbenzene
sulfonates
can
occur
from
mixing/
loading/
application
activities
in
various
use
sites,
including
agricultural
food
handling,
and
commercial/
institutional/
industrial
premises.

Of
the
approximate
30
million
pounds
of
alkylbenzene
sulfonates
produced
per
year,
0.1%
or
300,000
pounds
are
used
in
EPA
registered
antimicrobial
products.
The
rest
is
primarily
used
in
household
laundry
and
dish
detergents
annually.
The
alkylbenzene
sulfonates
are
listed
on
the
EPA
HPV
Challenge
Program.
HPV
chemicals
are
those
that
are
manufactured
or
imported
into
the
U.
S.
in
production
volumes
greater
than
one
million
pounds
per
year.
The
HPV
Challenge
Program
is
a
voluntary
partnership
between
industry,
environmental
groups,
and
the
EPA
which
invites
chemical
manufacturers
and
importers
to
provide
basic
hazard
data
on
the
HPV
chemicals
they
produce/
import.
The
goal
of
this
program
is
to
facilitate
the
Public's
right­
to­
know
about
the
potential
hazards
of
chemicals
found
in
their
environment,
their
homes,
their
workplace,
and
in
consumer
products.
The
alkylbenzene
sulfonates
are
sponsored
by
the
Linear
Alkylbenzene
(
LAB)
Sulfonic
Acids
Coalition,
which
has
generated
data
for
these
chemicals.

6.1
Summary
of
Registered
Uses
The
alkylbenzene
sulfonates
are
both
active
and
inert
ingredients
in
pesticide
products.
As
active
ingredients,
they
are
currently
in
twenty­
three
registered
end­
use
products
as
a
disinfectant,
food­
contact
sanitizer,
bacteriocide/
bacteriostat,
microbiocide/
microbiostat,
fungicide/
fungistat,
and
virucide.
Alkylbenzene
sulfonates
are
in
cleaners
and
sanitizers
that
are
designated
for
use
in
agricultural,
food
handling
and
commercial/
institutional/
industrial
settings.
Examples
of
registered
uses
for
alkylbenzene
sulfonates
include,
but
are
not
limited
to:
application
to
indoor
hard
surfaces
(
e.
g.
urinals,
shower
stalls,
toilet
bowls,
etc.),
food
dispensing
equipment
(
e.
g.
pre­
mix
and
post­
mix
vending
machines),
food
contact
surfaces
(
glasses,
dishes,
silverware,
countertops,
etc.),
agricultural
tools,
and
fruits
and
vegetables
(
post­
harvest).
As
active
Page
22
of
62
ingredients,
there
are
no
residential
or
outdoor
uses
currently
registered.
As
active
ingredients,
concentrations
of
alkylbenzene
sulfonates
in
products
range
from
0.036%
to
25.6%.
Products
containing
alkylbenzene
sulfonates
are
formulated
as
soluble
concentrates,
flowable
concentrates,
ready­
to­
use
solutions,
or
water
soluble
packaging.
The
application
rates
used
in
this
assessment
were
the
maximum
application
rates
as
recommended
on
the
product
labels.

As
inert
ingredients,
there
are
approximately
350
registered
end­
use
products
containing
these
chemicals.
Some
of
the
inert
functions
of
alkylbenzene
sulfonates
in
the
registered
products
are
listed
as
solvent,
surfactant,
dispersant,
detergent,
and
wetting
agent.
Products
that
contain
alkylbenzene
sulfonates
as
an
inert
are
designated
for
use
in
agricultural
settings,
food
handling
premises,
medical
premises,
commercial/
institutional/
industrial
settings,
and
residential
settings.
Some
examples
of
the
specified
use
sites
of
the
products
consist
of
indoor
hard
non­
porous
surfaces
(
e.
g.
floors,
walls
etc.),
carpets,
food
contact
surfaces
(
glasses,
dishes,
silverware,
countertops,
etc.),
agricultural
tools
and
crops,
lawns
and
turfs,
fruits
and
vegetables
(
post­
harvest),
wood
preservatives,
materials
preservatives,
metalworking
fluids,
and
pet
products.
Many
of
these
products
are
formulated
as
soluble
concentrates,
flowable
concentrates,
ready­
to­
use
solutions,
or
water­
soluble
packaging.

As
inert
ingredients,
the
percent
formulations
for
most
of
the
products
that
contain
alkylbenzene
sulfonates
as
an
inert
ingredient
range
from
0.01%
to
5%.
However,
the
majority
of
the
labels
in
this
range
contain
2%
alkylbenzene
sulfonates.
Therefore,
the
risks
were
assessed
at
2%
formulation,
which
represents
the
formulation
that
is
most
likely
to
be
used,
and
at
an
appropriate
high­
end
formulation,
which
is
dependent
upon
the
product
type.
It
should
be
noted
that
a
few
sanitizing
products
have
inert
levels
as
high
as
30%
and
the
highest
concentration
of
alkylbenzene
sulfonates
are
found
in
wood
preservative
products
up
to
65
%.

6.2
Dietary
Exposure
and
Risk
6.2.1
Dietary
Exposure
for
Active
Ingredient
Uses
Estimates
of
dietary
risk
from
the
use
of
alkylbenzene
sulfonates
as
active
ingredients
in
pesticide
products
are
based
upon
the
detailed
analysis
in
the
Dietary
Exposure
Assessment
memorandum
(
memo
from
R.
Quick,
March
2006,
D327731)
and
are
summarized
here
for
completeness.
Dodecylbenzenesulfonic
acid
(
27176­
87­
0)
and
sodium
dodecylbenzene
sulfonate
(
25155­
30­
0)
have
uses
in
food­
contact
surface
sanitizing
solutions
with
tolerance
exemptions
as
specified
in
40
CFR
180.940
(
b)
and
(
c),
and
summarized
in
the
Table
below.
Residues
for
these
compounds
are
exempt
from
the
requirement
of
a
tolerance
when
used
in
accordance
with
good
manufacturing
practice
as
ingredients
in
an
antimicrobial
pesticide
formulation,
provided
that
the
substance
is
applied
on
a
semi­
permanent
or
permanent
food­
contact
surface
(
other
than
being
applied
on
food
packaging)
with
adequate
draining
before
contact
with
food.
Both
dodecylbenzene
sulfonic
acid,
and
sodium
dodecylbenzene
sulfonate
have
limitations
for
the
ready­
to­
use
end­
use
concentration
not
to
exceed
400
ppm
and
430
ppm,
respectively
for
food
processing
equipment
and
utensils.
However,
dodecylbenzene
sulfonic
acid
has
a
much
lower
limitation
of
5.5
ppm
for
use
on
dairy
processing
equipment.
The
Agency
estimates
that
the
430
ppm
limitation
for
the
sodium
salt
is
equivalent
to
approximately
400
ppm
of
the
free
acid
form.
Page
23
of
62
Table
4.
Tolerance
Exemptions
for
Food
Contact
Sanitizer
Uses
(
Active
Uses)

Tolerance
Exemption
Expression/
Chemical
Name
CAS
No.
PC
Code
40
CFR

180.
Use
Pattern
(
Pesticidal)

940
(
b)
food
contact
sanitizing
solutions
for
dairy
processing
equipment,
and
food
processing
equipment
and
utensils;
end
use
concentration
not
to
exceed
5.5
ppm
Benzenesulfonic
acid,
dodecyl­
27176­
87­
0
098002
940
(
c)
food
contact
sanitizing
solutions
for
food
processing
equipment
and
utensils;
end
use
concentration
not
to
exceed
400
ppm
Benzenesulfonic
acid
dodecyl­,
sodium
salt
25155­
30­
0
079010
940
(
c)
food
contact
sanitizing
solutions
for
food
processing
equipment
and
utensils;
end
use
concentration
not
to
exceed
430
ppm
Based
on
the
pesticide
labels,
the
Agency
assessed
dietary
exposure
that
could
result
from
the
use
of
alkylbenzene
sulfonates
in
the
food
service
industry
(
treated
surfaces,
dishes,
utensils,
glassware,
pots
and
pans),
in
the
food
processing
industry
(
food
processing
equipment
such
as
breweries
and
beverage
plants,
meat
and
poultry
processing
plants,
milk
and
dairy
products/
packing
plants
etc),
and
as
a
fruit
and
vegetable
wash.

Food
Handling
Establishments.
In
the
absence
of
residue
data
for
residues
of
alkylbenzene
sulfonates
on
treated
food
contact
surfaces,
the
Agency
estimated
residue
levels
that
may
occur
in
food
from
the
application
rates
on
food
contact
surfaces.
To
determine
the
Estimated
Daily
Intake
(
EDI),
the
Agency
has
used
an
FDA
model.
The
maximum
ingredient
percentage
for
dodecylbenzene
sulfonates
in
food
handling
establishments
from
the
various
labels
is
400
ppm.
The
Agency
estimates
that
use
of
this
product
results
in
food
residues
of
530
ppb
(
µ
g/
kg).
The
Agency
assumed
that
food
can
contact
4000
cm2
of
treated
surfaces,
utensils,
glassware,
or
pots
and
pans
and
that
100%
of
the
pesticide
migrates
to
food
based
on
the
standard
assumptions
used
in
the
FDA
Sanitizing
Solution
Guidelines.
It
was
assumed
that
an
adult
and
child
consume
3000
and
1500
grams
of
food
per
day,
respectively
that
will
contact
the
treated
surfaces.

Food
Processing
Equipment.
The
Agency
used
the
FDA
milk
truck
model
to
estimate
residues
in
milk
that
could
result
from
the
use
of
alkylbenzene
sulfonates
in
the
food
processing
equipment,
as
representative
of
the
potential
uses
in
the
food
processing
industry.
As
a
conservative
measure,
the
Agency
assessed
the
maximum
application
rate
of
400
ppm
for
dodecylbenzene
sulfonates,
as
listed
on
the
labels,
although
the
current
tolerance
exemption
has
a
limitation
of
5.5
ppm
for
dairy
processing
equipment.
The
Agency
estimates
that
use
of
this
product
results
in
maximum
milk
residues
of
10
ppb
(
µ
g/
kg).

Fruit
and
Vegetable
Wash.
The
Agency
also
estimated
dietary
exposure
from
the
fruit
and
Page
24
of
62
vegetable
wash
of
the
alkylbenzene
sulfonates.
This
use
is
regulated
by
the
FDA
in
21
CFR
173.315,
which
permits
the
wash
solution
to
contain
dodecylbenzene
sulfonic
acid
up
to
0.2%
(
2000
ppm),
without
a
potable
rinse.
Most
of
the
pesticide
labels
are
in
compliance
with
this
limitation.
One
label
however,
allows
a
vegetable
wash
solution
containing
0.31%
(
3100
ppm)
dodecylbenzene
sulfonic
acid,
but
requires
a
potable
rinse
following
washing.

In
the
absence
of
data
for
residues
on
fruits
and
vegetables,
the
Agency
developed
a
model
and
used
a
number
of
conservative
assumptions.
The
Agency
assumed
the
maximum
application
rate
of
2000
ppm
in
wash
solution,
along
with
assumptions
for
Thompson
Seedless
grapes
as
a
surrogate
to
represent
residues
on
all
treated
fruits
and
vegetables.
The
model
estimates
dodecylbenzene
sulfonic
acid
residues
of
9.25
ppm,
which
were
used
to
estimated
dietary
exposure
using
the
Dietary
Exposure
Evaluation
Model
(
DEEM­
FDIC
 
)
,
Version
2.03
which
uses
food
consumption
data
from
the
USDA's
Continuing
Surveys
of
Food
Intake
by
Individuals
(
CSFII)
from
1994­
1996
and
1998.
This
assessment
is
Tier
1,
conservative
(
assumes
100%
of
fruits
and
vegetables
are
washed)
and
uses
the
deterministic
approach.

The
daily
estimates
for
the
above
three
use
patterns
were
conservatively
used
to
assess
chronic
dietary
risks,
which
are
shown
below
in
Table
5.
As
noted
previously,
an
acute
dietary
assessment
was
not
conducted
because
there
are
no
adverse
effects
attributable
to
a
single
dose
exposure.

The
dietary
risk
estimates
for
the
total
food
contact
sanitizing
uses
are
below
the
Agency's
level
of
concern
for
all
age
groups
(
less
than
11%
of
the
cPAD).
In
addition,
the
dietary
risk
estimates
for
the
fruit
and
vegetable
wash
for
adults
and
young
children
are
below
the
Agency's
level
of
concern
for
all
age
groups
(
less
than
71.2%
of
the
cPAD).
These
risk
estimates
are
based
on
a
number
of
conservative
assumptions,
and
thus
may
overestimate
the
actual
risks.

Table
5.
Summary
of
Dietary
Exposure
and
Risk
for
Alkylbenzene
Sulfonates
Pesticidal
Active
Uses
Chronic
Dietary
Use
Population
Subgroup
Dietary
Exposure
(
mg/
kg/
day)
a
%
cPAD
b
adult
male
0.023
4.6
females
(
13­
50
years)
0.027
5.4
Food
Service
Industry
(
treated
surfaces,
utensils,
glassware,
etc)

infants/
children
0.053
10.6
adult
male
0.00043
0.086
females
(
13­
50
years)
0.0005
0.1
Food
Processing
Industry
(
Food
Processing
Equipment)

infants/
children
0.001
0.2
adult
male
0.023
4.6
Total
Food
Contact
Surface
females
(
13­
50
years)
0.027
5.4
Page
25
of
62
Table
5.
Summary
of
Dietary
Exposure
and
Risk
for
Alkylbenzene
Sulfonates
Pesticidal
Active
Uses
Chronic
Dietary
Use
Population
Subgroup
Dietary
Exposure
(
mg/
kg/
day)
a
%
cPAD
b
Sanitizing
Uses
infants/
children
0.054
10.8
U.
S
population
0.0979
19.6
children
1­
2
yrs
0.3558
71.2
Fruit
and
Vegetable
Wash
children
3­
5
yrs
0.2573
51.5
NA=
not
applicable
a­­
chronic
exposure
analysis
based
on
body
weights
of
70
kg,
60
kg,
and
15
kg
for
adult
males,
females
and
children,
respectively.
b­­
%
PAD
=
dietary
exposure
(
mg/
kg/
day)
/
cPAD,
where
cPAD=
0.5
mg/
kg/
day
for
all
populations.

6.2.2
Dietary
Exposure
for
Inert
Ingredient
Uses
Included
in
this
risk
assessment
is
the
reassessment
of
the
alkylbenzene
sulfonates
when
used
as
an
inert
ingredient
in
pesticide
products.
Estimates
of
dietary
risk
from
the
inert
uses
of
alkylbenzene
sulfonates
are
based
upon
the
detailed
analysis
in
the
Inert
Ingredient
Dietary
Risk
Assessment
memorandum
(
memo
from
K.
Leifer,
March
2006,
D327731).
As
noted
previously,
some
of
the
inert
functions
of
alkylbenzene
sulfonates
in
the
registered
products
are
listed
as
solvent,
surfactant,
dispersant,
detergent,
and
wetting
agent.
Some
of
these
products
are
designated
for
use
in
agricultural
settings
(
i.
e.,
pre­
and
post­
harvest
and
when
applied
to
animals),
where
there
is
a
potential
for
dietary
exposure.

The
alkylbenzene
sulfonates
assessed
in
this
document
are
constituents
of
a
larger
group
of
compounds
that
have
a
tolerance
exemption
as
an
inert
ingredient
in
40
CFR
180.910
and
180.
930.
As
shown
in
Table
6,
the
tolerance
exemption
is
listed
as
Alkyl
(
C8­
C24)
benzenesulfonic
acid
and
its
ammonium,
calcium,
magnesium,
potassium,
sodium
and
zinc
salts.

Table
6.
Tolerance
Exemptions
for
Inert
Use
Tolerance
Exemption
Expression
40
CFR

180.
(
a)
Use
Pattern
910
Surfactants,
related
adjuvants
of
surfactants
Alkyl
(
C8­
C24)
benzenesulfonic
acid
and
its
ammonium,
calcium,
magnesium,
potassium
,
sodium
and
zinc
salts
930
Surfactants,
emulsifier,
related
adjuvants
of
surfactants
(
a)
Residues
listed
in
40
CFR
§
180.910
are
exempted
from
the
requirement
of
a
tolerance
when
used
as
inert
ingredients
in
pesticide
formulations
when
applied
to
growing
crops
or
to
raw
agricultural
commodities
after
harvest
(
i.
e.,
pre­
and
post­
harvest).
Residues
listed
in
40
CFR
§
180.930
are
exempted
from
the
requirement
of
a
tolerance
Page
26
of
62
when
used
as
inert
ingredients
in
pesticide
formulations
when
applied
to
animals
only.

Inert
Dietary
Exposure
Assumptions
and
Risk
Estimates
A
dietary
exposure
analysis
for
the
inert
ingredient
use
of
the
alkylbenzene
sulfonates
was
conducted
using
the
generic
screening
model
for
estimating
inert
ingredient
dietary
exposure.
The
dietary
assessment
is
unrefined
and
extremely
conservative
in
nature
because
the
screening
model
assumes
that
the
inert
ingredient
is
used
on
all
commodities,
and
that
100
percent
of
crops
are
treated
with
the
inert
ingredient,
with
no
limitation
on
the
fraction
of
inert
ingredient.
Further,
the
model
assumes
residues
will
be
present
for
every
consumed
commodity
(
including
meat,
milk,
poultry
and
eggs)
that
is
included
in
the
Dietary
Exposure
Evaluation
Model
(
DEEM
 
)
.
The
conservative
nature
of
this
assessment
is
believed
to
capture
all
potential
dietary
exposures,
including
those
from
direct
application
to
animals.

Based
on
the
use
of
the
screening
level
inert
ingredient
dietary
exposure
model,
there
are
no
risk
concerns
associated
with
dietary
exposures
as
the
estimated
dietary
exposures
for
the
U.
S.
population
and
all
population
subgroups
are
below
100%
of
the
cPAD.
As
noted,
a
number
of
conservative
assumptions
were
used
in
this
screening
level
dietary
risk
assessment1
of
inert
uses.

Table
7.
Summary
of
Dietary
Exposure
and
Risk
for
Alkylbenzene
Sulfonates
as
Inert
Ingredients
Chronic
Dietary
Population
Subgroup
Dietary
Exposure
(
mg/
kg/
day)
%
cPAD
a
U.
S.
population
0.12
24
females
(
13­
50
years)
0.087
17
children
1­
2
yrs
0.422
84
children
3­
5
yrs
0.31
62
a­­
%
PAD
=
dietary
exposure
(
mg/
kg/
day)
/
cPAD,
where
cPAD=
0.5
mg/
kg/
day
for
all
populations.

6.3
Drinking
Water
Exposure
and
Risk
for
Inert
Ingredient
Uses
There
are
no
currently
registered
outdoor
uses
of
the
alkylbenzene
sulfonates
as
active
ingredients
that
are
being
supported
by
the
registrant.
However,
these
compounds
are
inert
ingredients
in
many
residential
and
agricultural
products
that
are
used
outdoors.
The
majority
of
these
products
contain
alkylbenzene
sulfonates
at
low
concentrations
that
are
generally
less
than
1
A
review
of
those
products
listed
as
containing
ingredients
Benzenesulfonic
acid,
dodecyl­
(
CAS
Reg.
No.
27176­
87­
0);
Sodium
dodecylbenzenesulfonate
(
CAS
Reg.
No.
25155­
30­
0);
and
Benzenesulfonic
acid,
C10­
16­
alkyl
derivs
(
CAS
Reg.
No.
68584­
22­
5)
was
conducted.
The
results
of
that
review
indicate
that
the
linear
alkylbenzenesulfonates
are
primarily
used
in
low
concentrations
(
typically
less
than
5%
w/
w)
in
herbicide
products
that
typically
are
applied
in
a
preemergent
or
early
post­
emergent
fashion.
Page
27
of
62
5%.
Based
on
the
"
Environmental
Fate
Assessment
of
Alkylbenzene
Sulfonates
for
the
Registration
Eligibility
Document
(
RED)"
(
T.
Milano,
March
2006),
linear
alkyl
benzenesulfonates
are
water
soluble,
nonvolatile
and
mobile,
but
also
readily
biodegradable.
There
are
no
readily
available
data
on
the
occurrence
of
linear
alkyl
benzenesulfonates
in
ambient
or
treated
drinking
water.
No
ambient
water
quality
criteria,
drinking
water
maximum
contaminant
levels
or
health
advisory
levels
have
been
established
for
these
compounds
by
EPA's
Office
of
Water.
The
potential
for
transport
into
drinking
water
resulting
from
pesticide
inert
ingredient
uses
of
these
substances
do
exist,
therefore
the
Agency
estimated
drinking
water
concentrations
resulting
from
the
inert
ingredient
uses
of
these
substances.
Details
of
this
analysis
are
presented
in
the
Inert
Ingredient
Dietary
Risk
Assessment
memorandum
from
K.
Leifer,
March
23,
2006.

The
drinking
water
analysis
is
based
on
a
derivation
of
estimated
upper
bound
Tier
I
drinking
water
concentrations
from
these
substances'
use
as
pesticide
inert
ingredients
from
the
FQPA
Index
Reservoir
Screening
Tool
(
FIRST).
A
number
of
conservative
assumptions
were
utilized
as
inputs
into
the
inert
ingredient
drinking
water
exposure
assessment
model.
For
example,
it
was
assumed
that
the
linear
alkylbenzene
sulfonates
were
stable,
and
pesticide
products
were
applied
via
aerial
spray.
The
results
of
the
model
were
scaled
to
account
for
a
linear
alkylbenzene
sulfonate
weight
fraction
of
5%
(
which
is
a
95th
percentile
value).
The
Estimated
Drinking
Water
Concentration
(
EDWC)
for
chronic
drinking
water
exposure
is
6.6
ug/
L
(
ppb).

The
Agency
did
not
estimate
acute
drinking
water
risks
for
the
inert
ingredient
use
because
an
acute
dietary
endpoint
(
i.
e.,
aPAD)
was
not
selected
as
there
were
no
effects
attributable
to
a
single
dose
exposure.
The
estimated
chronic
drinking
water
concentration
and
drinking
water
level
of
concern
for
chronic
exposure
to
linear
alkyl
benzenesulfonates
is
given
in
Table
8
below.

Table
8.
Chronic
Drinking
Water
Exposure
Estimates
for
Inert
Ingredient
Uses
of
Alkylbenzene
Sulfonates
Population
Subgroup
EDWC1
(
µ
g/
L)
%
cPAD2
DWLOC3
(
µ
g/
L)
U.
S.
Population
(
total)
6.6
<
0.1%
38
­
1,500
Children
(
1­
2
years)
6.6
<
0.1%
8
­
500
1
Estimated
Drinking
Water
Concentration
(
EDWC)
for
chronic
drinking
water
exposure
as
determined
by
the
use
of
FIRST
modeling
analysis
described
above
for
inert
ingredient
use.
[
The
EDWC
for
linear
alkyl
benzenesulfonates
is
the
value
reported
as
the
"
Adjusted
Annual
Average
(
Chronic)
Untreated
Water
Concentration"
]
2
%
cPAD
=
drinking
water
exposure
(
mg/
kg/
day)
/
cPAD,
where
cPAD=
0.5
mg/
kg/
day
for
all
populations.
It
was
assumed
that
a
15
kg
child
ingests
1
L
water
per
day
and
that
a
70
kg
adult
ingests
2L
water
per
day.
3
Drinking
Water
Level
of
Comparison
(
DWLOC)
is
the
maximum
contribution
from
water
allowed
in
the
diet
based
on
food
and
drinking
water
from
inert
use
only.
In
this
case,
since
the
allowable
risk
contribution
from
food
is
based
on
a
screening
level
model,
the
use
of
a
single,
deterministic
value
for
the
DWLOC
is
not
appropriate.
Rather
a
DWLOC
range
is
given,
with
the
values
in
the
range
corresponding
to
an
upper
value
of
range
of
drinking
water
concentrations
ranging
from
100%
of
the
cPAD
(
i.
e.,
assuming
no
food
exposure)
to
a
lower
value
that
considers
food
exposures
to
be
at
the
dietary
screening
level
value.

For
chronic
drinking
water
exposures
to
linear
alkyl
benzenesulfonates
as
inert
ingredients,
the
Drinking
Water
Level
of
Comparison
(
DWLOC)
range
for
chronic
exposure
is
38­
1500
µ
g/
L
for
the
general
U.
S.
population
and
8­
500
µ
g/
L
for
children
1­
2
years
old.
The
EDWC
used
to
Page
28
of
62
assess
chronic
(
non­
cancer)
dietary
risk
from
drinking
water
is
6.6
µ
g/
L.
The
chronic
estimated
concentration
is
below
the
DWLOCs
for
the
general
U.
S.
population
and
all
population
subgroups.
Drinking
water
risks,
therefore,
are
not
of
concern.

The
Agency
concludes
that
there
are
no
risk
concerns
for
chronic
aggregate
dietary
and
drinking
water
exposures
to
the
alkylbenzene
sulfonates
as
pesticide
inert
ingredients.
This
is
based
on
the
conservative
assumptions
used
in
the
screening
level
dietary
exposure
model,
as
well
as
the
estimated
upper
bound
drinking
water
concentrations
from
these
substances'
use
as
pesticide
inert
ingredients
derived
from
FIRST.

6.4
Residential
Exposure
and
Risks
from
Inert
Ingredient
Use
Exposure
Scenarios
As
noted
previously,
there
are
no
residential
use
sites
for
the
alkylbenzene
sulfonates
as
active
ingredients.
However,
alkylbenzene
sulfonates
are
formulated
as
inert
ingredients
in
approximately
350
registered
end­
use
products,
many
of
which
are
used
in
residential
settings.
Some
examples
of
the
specified
use
sites
on
the
products
consist
of
indoor
hard
non­
porous
surfaces
(
e.
g.
floors,
walls
etc.),
carpets,
food
contact
surfaces
(
glasses,
dishes,
silverware,
countertops,
etc.),
agricultural
tools
and
crops,
lawns
and
turfs,
fruits
and
vegetables
(
post­
harvest),
wood
preservatives,
materials
preservatives,
metalworking
fluids,
and
pet
products.
Details
of
the
residential
inert
exposure
assessment
can
be
found
within
the
companion
memorandum
(
memorandum
from
T.
Milano./
C.
Walls
March
23,
2006.
D327733).
A
summary
of
the
residential
assessment
is
presented
below.

For
the
purposes
of
this
screening
level
assessment,
the
Agency
selected
representative
scenarios
for
the
vast
majority
of
products,
based
on
end­
use
product
application
methods
and
use
amounts.
These
scenarios
reflect
high­
end
exposure
and
risk
estimates
for
all
products
represented.
The
following
residential
use
sites
were
assumed
to
be
the
high­
end
representative
scenarios
for
inert
uses
of
alkylbenzene
sulfonates.
These
include:

1)
outdoor
residential
turf
treatment
(
ready
to
use
liquid),
2)
indoor
hard
surface
cleaner
(
ready
to
use
liquid),
3)
indoor
carpet
cleaner
(
ready
to
use
liquid),
and
4)
pet
flea
and
tick
products
(
aerosol
can
spray).

For
each
of
the
use
sites,
the
Agency
assessed
residential
handler
(
applicator)
inhalation
exposure
and
post
application
incidental
ingestion
by
toddlers.
Residential
postapplication
exposures
result
when
bystanders,
such
as
children
come
in
contact
with
alkylbenzene
sulfonates
in
areas
where
end­
use
products
have
recently
been
applied
(
e.
g.,
treated
hard
surfaces/
floors),
or
when
children
incidentally
ingest
the
residues
through
mouthing
the
treated
end
products/
treated
articles
(
i.
e.,
hand­
to­
mouth
or
object­
to­
mouth
contact).
As
previously
mentioned,
there
is
no
dermal
endpoint,
and
therefore,
there
were
no
dermal
assessments
conducted
(
handler
or
post
application).
Page
29
of
62
Exposure
Data
and
Assumptions
For
most
residential
scenarios,
the
Agency
used
EPA's
Pesticide
Inert
Risk
Assessment
Tool
(
PiRat)
to
estimate
residential
applicator
and
post­
application
exposures
and
risks
from
the
use
of
alkylbenzene
sulfonates
as
an
inert
ingredient
in
representative
residential
products.
Background
information
and
the
downloadable
executable
file
for
PiRat
can
be
found
at
http://
www.
epa.
gov/
opptintr/
exposure/
docs/
pirat.
htm.
The
Agency
utilized
all
of
PiRat's
default
values,
along
with
high­
end
percent
formulations
based
on
the
review
of
the
Confidential
Statements
of
Formula
(
CSFs)
for
the
various
residential
products
that
contain
the
alkylbenzene
sulfonates
as
inert
ingredients.
For
the
assessment
of
the
pet
products,
the
Agency
used
assumptions
in
the
Residential
Standard
Operating
Procedures
(
SOPs).
Typically,
most
products
used
in
a
residential
setting
result
in
exposures
occurring
over
a
short­
term
duration.
Thus,
the
residential
handler
and
postapplication
scenarios
are
assumed
to
be
of
short­
term
duration
(
1­
30
days).

Because
there
are
a
large
number
of
products
that
contain
alkylbenzene
sulfonates
as
an
inert
ingredient,
the
Agency
assessed
both
a
high
end
formulation
in
addition
to
a
2%
formulation
product.
The
2%
value
was
selected
because
the
majority
of
the
labels
contain
2%
alkylbenzene
sulfonates
as
an
inert
ingredient
An
inhalation
post­
application
assessment
was
not
conducted
because
the
vapor
pressure
of
the
alkylbenzene
sulfonates
is
extremely
low
(
5.1x10­
10
to
6x10­
15
mmHg).
In
addition,
a
dermal
assessment
was
not
conducted
because
of
the
lack
of
a
dermal
toxicological
endpoint.

Risk
Characterization
A
summary
of
the
residential
handler
exposure
and
risk
estimates
are
presented
on
Table
9,
while
the
postapplication
incidental
oral
exposure
and
risk
estimates
are
presented
in
Table
10.
The
non­
cancer
risk
estimates
are
expressed
in
terms
of
the
MOE.
For
residential
handlers
that
handle
products
containing
alkylbenzene
sulfonates
as
inert
ingredients,
the
short­
term
inhalation
MOEs
were
above
the
target
MOEs
(
i.
e.,
 
>
100)
and
thus,
do
not
exceed
the
Agency's
level
of
concern,
with
the
exception
of
the
flea
and
tick
product
where
the
MOE
was
87
for
the
high­
end
formulation
containing
24%
alkylbenzene
sulfonates.
This
scenario
is
conservative
because
it
assumes
a
person
treats
their
pet
with
0.5
cans
of
flea
product
that
contains
24%
alkylbenzene
sulfonates
every
day
for
a
month.
However,
there
are
no
risk
concerns
for
the
majority
of
pet
products
containing
2%
alkylbenzene
sulfonates.

There
are
no
residential
postapplication
risk
concerns
for
the
majority
of
household
products
that
contain
2%
alkylbenzene
sulfonates
as
an
inert
ingredient.
However,
there
are
potential
postapplication
incidental
oral
risks
to
young
children
resulting
from
indoor
use
of
products
that
may
contain
high­
end
formulations
that
contain
between
6
and
8%
alkylbenzene
sulfonates.
The
MOEs
are
30
and
40
for
hard
surface
and
carpet
cleaners,
respectively,
which
are
less
than
the
Agency's
target
MOE
of
100
(
Table
10).
However,
these
risk
estimates
are
considered
to
be
conservative
screening­
level
values,
based
on
products
that
contain
between
6­
8%
alkylbenzene
sulfonates.
The
vast
majority
of
products
contain
concentrations
2%.
The
postapplication
incidental
oral
risks
to
children
that
may
contact
a
treated
pet
are
not
of
concern
as
Page
30
of
62
the
range
of
MOEs
(
106
to
1,300)
is
above
the
target
MOE
of
100.

Alkylbenzene
sulfonates
are
considered
to
be
dermal
irritants
in
formulations
that
have
listed
amounts
generally
greater
than
20%.
Thus,
dermal
exposure
would
be
self­
limiting
due
to
dermal
irritation.
The
vast
majority
of
residential
products
contain
less
than
5%
alkylbenzene
sulfonates.
The
Agency
intends
to
consider
the
potential
for
irritation
in
recommended
labeling
language
of
pesticide
products
containing
the
alkylbenzene
sulfonates,
and
consider
available
dermal
toxicity
data
on
a
diluted
end­
use
formulation.
The
Agency
should
confirm
that
all
products
with
greater
than
20%
require
the
use
of
gloves.

Table
9.
Estimates
of
Inhalation
Exposures
and
Risks
to
Residential
Handlers
of
Alkylbenzene
Sulfonates
as
Inert
Ingredients
(
Short­
Term
Duration)

Product
Use
Application
Method
Area
Treated/
Quantity
Handleda
Inhalation
Exposure
(
mg/
kg/
day)
Range
of
Inhalation
MOEsc
(
Target
MOE
 
100)

Outdoor
Products
Low
pressure
handwand;
MLAP
1000
ft2/
day
(
spot)
7.07x10­
6
20,000
­
110,000
Hose
end
sprayer;
MLAP
2x104
ft2/
day
(
full
broadcast)
4.48x10­
5
3,100
­
17,000
Backpack;
MLAP
7.07x10­
6
20,00
0­
110,000
Ready
to
Use
Liquid
Turf
spot/
gardensb
Sprinkling
can;
MLAP
1000
ft2/
day
(
spot)

2.24x10­
6
63,000
 
340,000
Indoor
Products
Ready
to
Use
Liquid
(
hard
surface
cleaner)
d,
e,
g
1.37x10­
4
1,000
 
4,100
Ready
to
Use
Liquid
(
carpet
cleaner)
d,
f,
g
Low
pressure
handwand;
MLAP
0.5
gallons/
day
1.03x10­
4
1,400
 
4,100
Pet
Flea
and
Tick
Producth
Aerosol
Can
Spray
0.5
6
oz
can
1.61x10­
3
87
 
1,000
a:
Standard
PiRat
model
input
parameters,
except
for
pet
products,
which
are
based
on
an
AD
assumption.
b:
percent
formulation
used
=
2%
­
11%;
an
application
rate
of
0.00015
lb
product/
ft2
was
assumed
for
all
scenarios
and
the
body
weight
=
70kg.
c:
MOEs
=
NOAEL
/
exposure
where
inhalation
NOAEL
=
0.14
mg/
kg/
day
and
the
target
MOE
 
100
d:
Crack
and
crevice
was
used
as
the
representative
input
parameter
for
the
assessment
of
alkylbenzene
sulfonates
as
Page
31
of
62
an
inert
in
products
that
are
used
for
hard
surface
cleaners
or
carpet
cleaners.
e:
%
formulation
used
=
2%
to
8%
f:
%
formulation
used
=
2%
to
6%
g:
An
application
rate
of
8
lb/
gallon,
which
is
the
density
of
water,
was
assumed
for
all
scenarios
and
the
body
weight
=
70kg.
h=
%
formulation
=
2%
­
24%.

Table
10.
Summary
of
Short­
Term
Residential
Postapplication
Exposure
and
Risk
Estimates
from
Alkylbenzene
Sulfonates
as
Inert
Ingredientsa
Product
Use
Route
of
Exposure
Exposure
mg/
kg/
dayb
Range
of
MOEsc
(
Target
MOE
 
100
Ready
to
Use
Liquid
Turf
spot/
gardensd
1.08x10­
2
4,600
 
25,000
Ready
to
Use
Liquid
(
hard
surface
cleaner)
a,
e
1.67
30
­
120
Ready
to
Use
Liquid
(
carpet
cleaner)
a,
f
Incidental
ingestion:
hand
to
mouth
1.26
40
­
120
Pet
Flea
and
Tick
Productg
Incidental
ingestion:
hand
to
mouth
0.4739
106
 
1,300
a:
The
representative
use
sites
assessed
through
using
PiRAT,
for
incidental
oral
post
application
exposures
to
toddlers
are
turf
products,
hard
surface
cleaners,
and
carpet
cleaners.
b:
The
body
weight
used
in
this
calculation
was
15kg,
which
is
assumed
to
be
the
body
weight
of
a
toddler.
c:
MOEs
=
NOAEL
/
exposure
where
incidental
oral
NOAEL
=
50
mg/
kg/
day.
Target
MOE
 
100.
d:
%
formulation
used
=
2%
­
11%
e:
%
formulation
used
=
2%
­
8%
f:
%
formulation
used
=
2%
­
6%
g:
%
formulation
used
=
2%
­
24%

7.0
AGGREGATE
RISK
ASSESSMENTS
AND
RISK
CHARACTERIZATION
In
order
for
a
pesticide
registration
to
continue,
it
must
be
shown
that
the
use
does
not
result
in
"
unreasonable
adverse
effects
on
the
environment".
Section
2
(
bb)
of
FIFRA
defines
this
term
to
include
"
a
human
dietary
risk
from
residues
that
result
from
a
use
of
a
pesticide
in
or
on
any
food
inconsistent
with
standard
under
section
408..."
of
FFDCA.
As
mandated
by
the
FQPA
amendments
to
FIFRA
and
the
Federal
Food,
Drug
and
Cosmetic
Act
(
FFDCA),
the
Agency
must
consider
total
aggregate
exposure
from
food,
drinking
water
and
residential
sources
of
exposure
to
alkylbenzene
sulfonates.
Aggregate
exposure
is
the
total
exposure
to
a
single
chemical
(
or
its
residues)
that
may
occur
from
dietary
(
i.
e.,
food
and
drinking
water),
residential,
and
other
non­
occupational
sources,
and
from
plausible
exposure
routes
(
oral,
dermal,
and
inhalation).

Typically,
aggregate
risk
assessments
are
conducted
for
acute
(
1
day),
short­
term
(
1­
30
days),
intermediate­
term
(
1­
6
months)
and
chronic
(
6
months
to
lifetime)
exposures.
However,
an
acute
aggregate
assessment
was
not
conducted
because
there
are
no
adverse
effects
attributable
to
Page
32
of
62
acute
exposure.
An
intermediate­
term
aggregate
assessment
was
not
conducted
because
there
are
no
residential
exposures
of
this
duration.
In
addition,
because
there
are
no
long­
term
residential
exposures,
the
chronic
aggregate
assessment
only
considered
food
and
drinking
water.
Thus,
only
short­
term
and
chronic
aggregate
assessments
were
conducted.
Oral
and
inhalation
exposure
and
risk
estimates
were
conservatively
combined
for
the
aggregate
risk
assessment
because
these
endpoints
both
identify
adverse
effects
on
body
weight.
Dermal
exposures
were
not
considered
in
the
risk
assessment
because
a
toxicological
endpoint
was
not
established.

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

Short­
Term
Aggregate
Risk.
Aggregate
short
term
risk
assessments
are
designed
to
provide
estimates
of
risk
likely
to
result
from
exposures
to
the
pesticide
or
pesticide
residues
in
food,
water,
and
from
residential
(
or
other
non­
occupational)
pesticide
uses.
This
assessment
considers
both
the
active
and
inert
uses
of
the
alkylbenzene
sulfonates.
For
children,
the
short­
term
aggregate
assessment
includes
average
dietary
exposure
(
food
and
drinking
water)
from
both
the
active
food
contact
sanitizer
uses
and
the
inert
uses
on
agricultural
commodities,
in
addition
to
estimated
incidental
oral
exposures
to
children
from
residential
uses
such
as
flea
and
tick
products
as
an
inert
ingredient.
For
adults,
the
aggregate
assessment
includes
dietary
(
food
and
drinking
water)
from
both
active
and
inert
uses
and
residential
inhalation
exposures
from
wiping
a
hard
surface
cleaning
products
since
this
scenario
represents
the
highest
exposure
from
the
inert
use.

Individual
scenarios
that
had
risks
of
concern
were
not
included
in
the
aggregate
assessment.
These
include
exposure
to
some
of
the
high­
end
formulation
products
such
as
the
residential
handler
of
pet
flea
and
tick
products
(
inhalation
MOE
is
87
compared
to
target
MOE>
100),
postapplication
incidental
oral
exposure
to
residues
on
floors
from
hard
surface
cleaners
or
carpet
cleaners
(
oral
MOEs
are
30
and
40,
respectively
compared
to
target
MOE>
100).
As
noted
previously,
a
number
of
very
conservative
assumptions
were
used
to
derive
these
risk
estimates.
However,
as
shown
on
Table
11,
the
aggregate
assessment
included
exposure
to
household
products
that
contain
2%
alkylbenzene
sulfonates
as
an
inert
ingredient.

Aggregate
risks
were
calculated
using
the
total
MOE
approach
outlined
in
OPP
guidance
for
aggregate
risk
assessment
(
August
1,
1999,
Updated
"
Interim
Guidance
for
Incorporating
Drinking
Water
Exposure
into
Aggregate
Risk
Assessments").
The
assumptions
and
equations
are
presented
in
the
footnotes
on
Table
11.
Page
33
of
62
Table
11
presents
a
summary
of
the
short­
term
aggregate
risk
MOEs.
The
aggregate
oral
and
inhalation
risks
are
not
of
concern
for
adults,
as
the
total
aggregate
MOE
is
340
which
is
greater
than
the
target
of
100.
For
children,
the
aggregate
risk
estimates
are
less
than
the
target
MOE
of
100
(
MOE=
54)
and
are
of
risk
concern.
The
aggregate
child
risks
are
of
concern
because
both
the
dietary
and
residential
scenarios
alone
are
very
close
to
the
target
MOEs
or
100%
of
the
cPAD
(
i.
e.,
food
and
drinking
water
accounts
for
approximately
95%
of
the
cPAD),
while
the
hard
surface
cleaner
postapplication
MOE
is
120.
As
noted
previously,
several
conservative
assumptions
were
used
in
this
assessment.
For
example,
dietary
exposure
from
both
the
active
sanitizer
use
and
the
inert
uses
were
considered
together
to
estimate
an
upper­
bound
exposure
estimate,
since
these
use
patterns
are
very
different
and
thus
could
co­
occur.
To
compensate
for
this
conservative
assumption,
the
Agency
only
included
one
representative
residential
use
scenario
in
the
aggregate
assessment
even
though
these
compounds
are
used
extensively
as
inert
ingredients
in
approximately
350
pesticide
products.

It
should
also
be
recognized
that
the
majority
of
the
uses
of
alkylbenzene
sulfonates
are
not
in
pesticide
products,
but
rather
are
used
in
household
laundry
and
dish
detergents.
Over
30
millions
pounds
of
these
compounds
are
produced
each
year,
while
only
300,000
pounds
are
used
in
EPA
registered
antimicrobial
products.
The
Agency
did
not
consider
potential
exposure
and
risks
from
the
numerous
other
residential
exposures
to
alkylbenzene
sulfonates
because
the
Agency
lacks
reliable
information
at
this
time.

Table
11
Summary
of
Short­
Term
Aggregate
Risk
Estimates
Dose
a
(
mg/
kg/
day)
Total
MOEb
(
Target
MOE 
100)
Exposure
Scenario
Child
(
15
kg)
Adult
Child
(
15
kg)
Adult
Oral
Exposure
Dietary
Exposure
Food
Contact
Sanitizer
0.054
0.027
926
(
10.8%
of
cPAD)
1,850
(
5.4%
of
cPAD)
Inert
Ingredient
Uses
(
Food)
0.422
0.12
118
(
84%
of
cPAD)
417
(
24%
of
the
cPAD)
Drinking
Water
Exposure
(
Inert)
c
0.00044
0.000189
114,000
(<
1%
of
cPAD
227,000
(<
1%
of
cPAD)
Hard
Surface
Cleaner
(
2%
Inert)
0.42
NA
120
NA
Inhalation
Exposure
Handler
of
hard
surface
cleaning
products
(
2%
Inert)
NA
0.000137
NA
1,000
Total
Aggregate
Dose
and
MOE
0.916
0.147
54
340
NA=
Not
applicable
(
a)
Chronic
dietary
exposure
for
females
13­
50
years
for
sanitizer
use.
The
total
general
population
dietary
exposure
was
used
to
assess
inerts,
since
this
population
has
higher
exposure
than
females
13­
50
years.
(
b)
MOE
=
NOAEL
(
mg/
kg/
day)
/
potential
dose
rate
(
mg/
kg/
day)
[
Where
short­
term
oral
NOAEL
=
50
mg/
kg/
day].
Target
MOE
 
100.
(
c)
Exposure
estimates
assume
a
15
kg
child
ingests
1L
water/
day
and
that
a
60
kg
adult
female
ingests
2L
water
per
Page
34
of
62
day
of
6.6
ppb
(
the
chronic
estimated
drinking
water
concentration
(
EDWC)
based
on
the
inert
ingredient
use.

Chronic
Aggregate
Risk.
The
chronic
aggregate
assessment
considers
average
dietary
exposure
(
food
and
drinking
water)
from
both
the
active
food
contact
sanitizer
uses
and
the
inert
uses
on
agricultural
commodities.
The
dietary
exposures
from
the
fruit
and
vegetable
wash
were
not
considered
because
it
would
be
overly
conservative
to
assume
simultaneous
exposure
to
alkylbenzene
sulfonates
from
three
different
use
patterns.
As
shown
on
Table
12,
the
dietary
aggregate
risk
is
95%
of
the
cPAD
for
children,
while
for
adults
it
is
29%
of
the
cPAD.

Table
12
Summary
of
Chronic
Aggregate
Risk
Estimates
Dose
a
(
mg/
kg/
day)
%
cPADb
Exposure
Scenario
Child
(
15
kg)
Adult
Child
(
15
kg)
Adult
Oral
Exposure
Dietary
Exposure
Food
Contact
Sanitizer
0.054
0.027
10.8%
5.4%
Inert
Ingredient
Uses
(
Food)
0.422
0.12
84%
24%
Drinking
Water
Exposure
(
Inert)
c
0.00044
0.000189
<
1%
<
1%

Total
Aggregate
Dose
and
Risk
0.476
0.147
95%
29%

NA=
Not
applicable
(
a)
Chronic
dietary
exposure
for
females
13­
50
years
for
sanitizer
use.
The
total
general
population
dietary
exposure
was
used
to
assess
inerts,
since
this
population
has
higher
exposure
than
females
13­
50
years.
(
b)
%
cPAD
=
dietary
exposure
(
mg/
kg/
day)
/
cPAD,
where
cPAD
­=
0.5
mg/
kg/
day
for
all
populations.
(
c)
Exposure
estimates
assume
a
15
kg
child
ingests
1L
water/
day
and
that
a
60
kg
adult
female
ingests
2L
water
per
day
containing
6.6
ppb
alkylbenzene
sulfonates.
The
6.6
ppb
estimate
is
based
on
the
chronic
estimated
drinking
water
concentration
(
EDWC))
resulting
from
agricultural
use
of
products
that
contain
the
alkylbenzene
sulfonates
as
an
inert
ingredient.

8.0
CUMULATIVE
EXPOSURE
AND
RISK
Another
standard
of
section
408
of
the
FFDCA
which
must
be
considered
in
making
an
unreasonable
adverse
effect
determination
is
that
the
Agency
considers
"
available
information"
concerning
the
cumulative
effects
of
a
particular
pesticide's
residues
and
"
other
substances
that
have
a
common
mechanism
of
toxicity."

Unlike
other
pesticides
for
which
EPA
has
followed
a
cumulative
risk
approach
based
on
a
common
mechanism
of
toxicity,
EPA
has
not
made
a
common
mechanism
of
toxicity
finding
as
to
the
alkylbenzene
sulfonates
and
any
other
substances
and
the
alkylbenzene
sulfonates
do
not
appear
to
produce
a
toxic
metabolite
produced
by
other
substances.
For
the
purposes
of
this
tolerance
action,
therefore,
EPA
has
not
assumed
that
alkylbenzene
sulfonates
have
a
common
mechanism
of
toxicity
with
other
substances.
For
information
regarding
EPA's
efforts
to
determine
which
chemicals
have
a
common
mechanism
of
toxicity
and
to
evaluate
the
cumulative
Page
35
of
62
effects
of
such
chemicals,
see
the
policy
statements
released
by
EPA's
Office
of
Pesticide
Programs
concerning
common
mechanism
determinations
and
procedures
for
cumulating
effects
from
substances
found
to
have
a
common
mechanism
on
EPA's
website
at
http://
www.
epa.
gov/
pesticides/
cumulative/.

9.0
OCCUPATIONAL
EXPOSURE
AND
RISK
The
Agency
has
assessed
the
exposures
and
risks
to
occupational
workers
that
handle
alkylbenzene
sulfonates
(
memorandum
from
T.
Milano,
January
2006).
This
section
summarizes
the
results
of
the
occupational
exposure
assessment.

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

Occupational
Handlers.
The
Agency
has
determined
that
there
is
potential
for
dermal
and
inhalation
worker
exposure
to
alkylbenzene
sulfonates
at
various
use
sites
including
agricultural
premises,
food
handling,
and
commercial/
institutional/
industrial
premises.
Representative
scenarios
were
selected
for
evaluation
based
on
the
use
sites
and
maximum
application
rates
for
all
three
of
the
active
ingredients
in
this
assessment.

As
noted
previously,
the
Agency
did
not
select
a
dermal
endpoint,
and
thus
only
inhalation
exposure
and
risk
estimates
are
presented.
The
alkylbenzene
sulfonates
are
dermal
irritants,
and
all
of
the
labels
require
the
use
of
gloves
by
workers,
except
for
Reg.
#
71094­
2
(
0.036%
ai,
ready
to
use
product).
The
occupational
exposure
scenarios,
and
estimated
risks
are
presented
in
Table
13.

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

For
the
occupational
handler
inhalation
risk
assessment,
the
short­
and
intermediate­
term
risks
calculated
at
baseline
exposure
(
no
respirators)
were
above
target
MOEs
for
all
scenarios
(
i.
e.,
inhalation
MOEs
were
>
100),
except
the
following:

 
ST
and
IT
inhalation
exposure
from
cleaning
hard
surfaces
via
circulation/
flow/
flushing
in
the
agricultural
premises
and
equipment
category,
inhalation
MOE
<
1.
 
ST
and
IT
inhalation
exposure
from
application
to
hard
surfaces
via
(
1)
circulation
systems/
flow
method,
or
(
2)
Cleaning
in
Place
(
CIP)
in
the
food
handling
category,
inhalation
MOE
<
1.
 
ST
and
IT
inhalation
exposure
from
cleaning
hard
surfaces
via
wiping
in
the
food
handling
category,
inhalation
MOE
=
93.
Page
36
of
62
 
ST
and
IT
inhalation
exposure
from
cleaning
food
dispensing
equipment
via
circulation
systems/
flow
method
in
the
food
handling
category,
inhalation
MOE
<
1.
 
ST
and
IT
Inhalation
exposure
from
cleaning
shower
stalls
and
toilets
via
(
1)
a
liquid
pour
application
or
(
2)
wiping
in
the
commercial/
institutional
premises,
inhalation
MOE
=
13
and
MOE
<
1,
respectively.

The
Agency
also
calculated
a
total
MOE
for
one
of
the
active
ingredients,
sodium
dodecylbenzene
sulfonate
(
25155­
30­
0)
based
on
the
label
use
directions,
which
recommend
the
same
product
be
used
for
both
cleaning
and
sanitizing.
As
shown
on
Table
14,
all
total
inhalation
MOEs
for
cleaning
and
sanitizing
(
baseline)
were
above
the
target
MOEs
for
all
scenarios
(
i.
e.,
inhalation
MOEs
were
>
100),
except
the
following:

 
ST
and
IT
inhalation
exposure
from
cleaning
indoor
hard
surfaces
via
wiping
and
then
following
with
sanitizing
via
immersion/
flooding
in
the
food
handling
premises
category,
inhalation
MOE
=
93.
 
ST
and
IT
inhalation
exposure
from
cleaning
indoor
hard
surfaces
via
wiping
and
then
following
with
sanitizing
via
low
pressure
spray
in
the
food
handling
premises
category,
inhalation
MOE
=
90.
 
ST
and
IT
inhalation
exposure
from
cleaning
indoor
hard
surfaces
via
sponge/
mesh/
wiping
and
then
sanitizing
via
immersion/
flooding
in
the
food
handling
premises
category,
inhalation
MOE
=
90.
 
ST
and
IT
inhalation
exposure
from
cleaning
and
sanitizing
steps
to
be
conducted
through
CIP
(
Cleaning
in
Place)
in
the
food
handling
premises
category,
inhalation
MOE
=
<
1.

Although
all
the
inhalation
risks
of
concern
are
for
baseline
exposures,
the
Agency
does
not
believe
it
is
practicable
to
require
the
use
of
respiratory
protection
on
cleaning
products
used
in
janitorial
situations.
In
addition,
engineering
controls
are
not
feasible
for
the
current
use
patterns
on
the
labels.

Table
13
Short­,
and
Intermediate­
Term
Inhalation
Risks
for
Occupational
Handlers
(
Representative
Scenarios)
Exposure
Scenario
Method
of
Application
Application
Rate
(
lb
ai/
gallon)
Quantity
Handled/
Treated
per
day
(
gallons)
Baseline
Inhalation
MOE
(
a)
(
Target
MOE 
100)

Agricultural
Premises
and
Equipment
Brush
0.0667
0.26
2,000
Mechanical
Foam
0.0667
0.26
430
Flooding
0.00183
10
280
Circulation,
flow,
flushing
0.00195
10,000
<
1
High
Pressure
spray
0.00326
40
630
Immersion
0.00334
10
160
Application
to
hard
surfaces
Fogger
Low
pressure
spray
0.00334
10
430
Page
37
of
62
Table
13
Short­,
and
Intermediate­
Term
Inhalation
Risks
for
Occupational
Handlers
(
Representative
Scenarios)
Exposure
Scenario
Method
of
Application
Application
Rate
(
lb
ai/
gallon)
Quantity
Handled/
Treated
per
day
(
gallons)
Baseline
Inhalation
MOE
(
a)
(
Target
MOE 
100)

Trigger
Pump
Spray
0.00334
0.26
8,700
Food
Handling
Brush
0.0667
0.26
2,000
Mechanical
Foam
0.0667
0.26
430
circulation,
flushing,
flow
method
0.00334
10,000
<
1
Immersion
0.00334
10
160
Trigger
Pump
Spray
0.00334
0.26
8,700
Low
pressure
handwand
(
clean)
0.00603
2
1,200
High
pressure
spray
(
sanitize)
0.0115
40
180
Immersion,
flooding
for
RTU
(
sanitize)
0.003
10
170
Mopping
0.00244
2
840
Wiping
(
clean)
0.00603
0.26
93
Sponge/
mesh
wipe
(
clean)
0.003
0.26
190
Application
to
indoor
hard
surfaces
Cleaning
in
Place
(
CIP)
(
clean
and
sanitize)
0.00358
10,000
<
1
Circulation
systems,
Flow
method
0.00334
10,000
<
1
Food
dispensing
equipment
Circulation
system
0.00603
10,000
680
Immersion
0.00455
10
110
Fruits
and
vegetables
Trigger
pump
spray
0.003
0.26
9,700
Commercial/
Institutional
Premises
Brush
0.0667
0.26
2,000
Mechanical
Foam
0.0667
0.26
430
Immersion
0.00334
10
160
Low
Pressure
Handwand
0.00334
2
2,200
Application
to
indoor
hard
surfaces
(
includes
utensils
and
silverware)
Trigger
Pump
Spray
0.00334
0.26
8,700
Mopping
0.0177
2
120
Liquid
pour
1.49
0.26
13
Shower
stalls
and
toilets
Wiping
1.49
0.26
<
1
(
a)
MOE
=
NOAEL
(
mg/
kg/
day)
/
Daily
Dose
[
Where
short­
and
intermediate­
term
NOAEL
=
0.14
mg/
kg/
day
for
inhalation
exposure]
Target
MOE
is
 
100.
Page
38
of
62
Table
14
Short,
and
Intermediate
Term
Inhalation
Risks
to
Occupational
Handlers
Cleaning
and
Sanitizing
with
Products
That
Contain
Sodium
Dodecylbenzene
Sulfonate
Representative
Use
Registration
#
Method
of
CLEANING
Application
(
Baseline
MOE)
Method
of
SANITIZING
Application
(
Baseline
MOE)
Total
Inhalation
MOE
(
Baseline)
(
Target
MOE 
100)

Food
Handling/
Storage
Establishments
Premises
and
Equipment
High
pressure
spray
(
180)
150
High
pressure
spray
(
1,100)
Brush
(
12,000)
1,000
High
pressure
spray
(
180)
180
1020­
13
Brush
(
75,000)
Brush
(
12,000)
10,000
Immersion/
Flooding
(
1.4X106)
1,200
Low
pressure
spray
(
1,200)

Low
pressure
spray
(
2,400)
800
Immersion/
Flooding
(
1.4X106)
93
Wiping
(
93)

Low
pressure
spray
(
2,400)
90
Immersion/
Flooding
(
1.4X106)
4,800
Foam
(
4,000)

Low
pressure
spray
(
2,400)
1,600
Immersion/
Flooding
(
1.4X106)
22,000
71094­
1
Brush
(
22,000)

Low
pressure
spray
(
2,400)
2,000
Immersion/
Flooding
(
170)
90
Sponge/
Mesh/
Wiping
(
190)
Trigger
Pump
(
9,700)
190
Immersion/
Flooding
(
170)
160
Low
Pressure
Spray
(
2,400)
Trigger
Pump
(
9,700)
1,900
Immersion/
Flooding
(
170)
170
71094­
2
Brush
(
45,000)

Trigger
Pump
(
9,700)
8,000
Indoor
Hard
Surfaces
(
includes
dishes
and
silverware)

1020­
13
CIP
(<
1)
CIP
(<
1)
<
1
Food
dispensing
equipment
71094­
1
Circulation
system
(
680)
Circulation
system
(
1,400)
450
Postapplication
Exposure
and
Risk.
For
most
of
the
occupational
scenarios,
postapplication
dermal
exposure
is
not
expected
to
occur
or
is
expected
to
be
negligible
based
on
Page
39
of
62
the
application
rates
and
chemical
properties
of
these
chemicals.
The
alkylbenzene
sulfonates
have
a
low
vapor
pressure
(
5.1x10­
10
to
6.02x10­
15
mmHg),
so
that
any
standing
solutions
that
may
result
in
post
application
exposure
were
deemed
negligible.

10.0
ENVIRONMENTAL
RISK
10.1
Active
Ingredient
Uses
A
detailed
ecological
hazard
and
environmental
risk
assessment
for
the
alkylbenzene
sulfonates
is
presented
in
the
attached
memorandum
for
the
active
ingredient
pesticidal
uses
(
memo
from
R.
Petrie,
January
2006).
A
brief
summary
is
presented
below.

Ecological
Toxicity
Data.

Acute
toxicity
to
terrestrial
organisms:
As
shown
in
the
acute
toxicity
summary
Table
10,
alkylbenzene
sulfonates
are
slightly
toxic
to
the
Northern
bobwhite
quail
on
an
acute
oral
basis.
The
avian
acute
oral
LD50
is
>
500
ppm,
therefore,
an
avian
environmental
hazard
statement
for
birds
is
not
required
on
manufacturing
use
product
labels.
No
evidence
of
endocrine
disrupting
effects
was
observed
in
mammalian
toxicity
studies.
No
data
are
available
or
required
for
terrestrial
plants.

Acute
toxicity
to
aquatic
organisms:
As
shown
in
Table
15,
supplemental
acute
studies
indicate
that
alkylbenzene
sulfonates
are
moderately
toxic
to
freshwater
fish
and
slightly
to
highly
toxic
to
freshwater
aquatic
invertebrates
depending
on
the
length
of
the
carbon
chain.
Literature
for
aquatic
species
indicates
that
alkylbenzene
sulfonate
formulations
are
more
toxic
the
higher
the
number
of
carbon
chains.
Alkylbenzene
sulfonate
antimicrobial
formulations
are
comprised
primarily
of
C10
to
C14
chains
(
DDBSA
Task
Force).
No
acute
fish
toxicity
data
are
available
for
carbon
chains
above
12.
Therefore,
a
fish
environmental
hazard
label
statement
is
required
on
manufacturing
use
product
labels.
Based
on
study
MRID
47025025,
an
environmental
hazard
statement
for
aquatic
invertebrates
is
required
on
manufacturing
use
products
because
the
EC50
is
<
1.0
ppm
(
C14,
C16).

Chronic
toxicity
to
aquatic
organisms:
A
28
day
chronic
freshwater
fish
toxicity
test
was
found
in
the
literature.
The
NOAEC
was
0.7
mg/
L
for
a
carbon
chain
C11.7
(
Fairchild
et
al,
1993).
Scientists
studying
alkylbenzene
sulfonates
have
concluded
that
a
laboratory
derived
NOAEC
of
0.4
mg/
L
alkylbenzene
sulfonates
is
protective
of
ecosystem
structure
and
function
in
experimental
streams.
Alkylbenzene
sulfonates
literature
indicates
slight
toxicity
to
green
algae.

Table
15.
Acute
Toxicity
of
Alkylbenzene
Sulfonates
Species
Chemical,
%
active
ingredient
(
ai)
Endpoint
Toxicity
Category
(
TGAI)
Satisfies
Guidelines/
Co
mments
Reference
Birds
Northern
bobwhite
87.6%
Carbon
chain
not
identified.
LD50
>
1382
mg/
kg
Slightly
toxic
Yes.
Acceptable.
MRID:

41143901
Page
40
of
62
Table
15.
Acute
Toxicity
of
Alkylbenzene
Sulfonates
Species
Chemical,
%
active
ingredient
(
ai)
Endpoint
Toxicity
Category
(
TGAI)
Satisfies
Guidelines/
Co
mments
Reference
(
Colinus
virginianus)
(
Nacconal
90G
used)
NOEL
=
279
mg/
kg
14
day
test
Freshwater
Fish
Fathead
Minnow
(
Pimephales
promelas)
14.0%
(
Carbon
chain
not
identified.)
96hr
LC50
=

3.4
mg/
L
Moderately
toxic
No.
Supplemental
study.
44260002
Rainbow
trout
Oncorhynchus
mykiss)
65.0%
C11,
C12
96
hr
LC50
=
1.68
mg/
L
Moderately
toxic
No.
Supplemental
study.
44260009
Freshwater
Invertebrates
Waterflea
(
Daphnia
magna)
Not
reported.
48­
hr.
EC50
=
LAS­
C10
=
29.5
mg/
L,
LAS­
C12
=
6.84
mg/
L,
LAS­
C14
=
0.80
mg/
L,
LAS­
C16
=
0.20
mg/
L.
C­
10
=
Slightly
toxic,
C14
=
highly
toxic.
No.
Supplemental
study.
47025025
Green
Algae
Selenastrum
capricornutum
Not
Reported.
(
Carbon
chain
not
identified.)
96
hr.
EC50
=
70.27
ppm
Slightly
toxic
No.
Supplemental.
42439803
Data
Requirements:
The
guideline
requirements
for
a
freshwater
fish
acute
test
(
Guideline
850.1075),
and
freshwater
invertebrate
(
Guideline
850.1010)
have
not
been
fulfilled,
and
are
required
to
support
the
current
indoor
uses.
Acute
estuarine/
marine
tests,
chronic
toxicity
testing
(
Fish
early
life
stage,
850.1300/
72­
4a
and
aquatic
invertebrate
life
cycle,
850.1400/
72­
4b)
and
non­
target
plant
phytotoxicity
tests
are
not
required
for
indoor
uses.

Environmental
Fate
and
Exposure
Assessment.

No
fate
studies
for
alkylbenzene
sulfonates
are
available
in
US
EPA's
files.
Thus,
the
Agency
has
relied
on
scientific
literature
and
the
Agency's
EPI
Suite
model
to
obtain
different
environmental
properties
for
the
alkylbenzene
sulfonates.
The
EPI
Suite
model
predicts
that
alkylbenzene
sulfonates
are
not
likely
to
persist
in
water
or
microbial
soils
and
sediments.
The
Agency
also
conducted
a
literature
search
to
further
support
the
output
parameters
that
were
provided
by
the
EPI
Suite
model.
Extensive
literature
are
available
that
describe
the
fate
and
significance
of
alkylbenzene
sulfonates
in
the
environment
from
a
long
history
of
detergent
use.

Environmental
exposure
modeling
was
not
conducted
for
alkylbenzene
sulfonic
acids
and
Page
41
of
62
sulfonates
because
the
currently
registered
uses
are
indoor
spray
applications.
Uses
such
as
urinals
and
toilet
bowls
could
result
in
minimal
exposure
to
the
environment
when
flushed,
however,
significant
environmental
exposure
is
not
expected
for
the
following
reasons:
total
alkylbenzene
sulfonate
usage
for
these
industrial
applications
is
very
minor
­
a
very
small
percentage
of
the
total
pounds
used
in
antimicrobials;
commercial
only
use
precludes
broad
environmental
exposures
that
might
occur
with
residential
use;
applications
are
mostly
sprayed
on
and
allowed
to
air
dry;
alkylbenzene
sulfonate
breakdown
and
degrade
rapidly
in
the
environment;
alkylbenzene
sulfonates
are
significantly
reduced
by
sewage
treatment;
and
industrial
water
treatment
requires
a
NPDES
permit
in
order
to
discharge
effluents.

Ecological
Risk
Characterization.

Sodium
dodecylbenzene
sulfonate,
and
DDBSA
are
unlikely
to
bioaccumulate
in
the
environment
or
aquatic
animals
and
are
expected
to
be
soluble
in
water
such
that
they
will
exhibit
mobility
through
the
soil.
Available
modeling
and
literature
suggest
that
these
chemicals
will
most
likely
biodegrade
rapidly
in
soil
due
to
microbial
degradation.
Minimal
or
no
environmental
exposure
to
terrestrial
or
aquatic
organisms
is
expected
to
occur
from
the
majority
of
alkylbenzene
sulfonate
antimicrobial
indoor
pesticide
uses
given
that
only
a
very
small
number
of
total
DDBSA
pounds
are
used
for
these
purposes.

Linear
alkyl
benzene
sulfonates
(
LAS)
have
been
the
principal
ingredient
in
laundry
detergent
for
30+
years.
Volume
12
(
10)
of
the
1993
issue
of
Environmental
Toxicology
and
Chemistry
featured
a
series
of
papers
on
environmental
impacts
of
LAS
in
a
special
symposium:
Surfactants
and
Their
Environmental
Safety
­
convened
by
R.
A.
Kimerle,
N.
T.
De
Oude
and
T.
W.
La
Point.
Two
papers
provide
excellent
summaries
of
ecotoxicity
endpoints
from
literature,
and
feature
laboratory
vs
field
analysis
of
detergent
generated
LAS
impacts
on
aquatic
organisms.
An
assessment
of
short
and
long­
term
impacts
of
LAS
detergents
on
the
environment
was
conducted.
Increases
and
decreases
in
natural
periphyton
community
abundance
were
observed,
but
determined
to
be
insignificant
for
the
three
major
species
evaluated:
Amphora
perpusilla,
Navicula
minima,
and
Schizothrix
calcicola
(
Lewis
et
al,
1993).
Monitoring
indicates
that
concentrations
of
0.230
mg/
L
(
continuous
criterion
concentration)
and
0.625
mg/
L
(
criterion
maximum
concentration)
are
rarely
exceeded
in
aquatic
systems
protected
by
activated
sludge
treatment
systems.
Ecotoxicity
studies
indicate
that
a
laboratory
derived
NOAEC
value
of
0.40
mg/
L
for
LAS
is
protective
of
structure
and
function
of
experimental
streams
(
Fairchild
et
al,
1993).

No
environmental
exposure
is
expected
to
occur
from
the
majority
of
linear
alkylbenzene
sulfonate
uses
and
it
is
unlikely
that
any
appreciable
exposure
to
terrestrial
or
aquatic
organisms
would
occur
from
limited
commercial
down­
the­
drain
use
because
of
the
very
small
number
of
pounds
sold
for
these
uses
plus
rapid
degradation
in
the
environment.

Endangered
Species
Considerations
Section
7
of
the
Endangered
Species
Act,
16
U.
S.
C.
Section
1536(
a)(
2),
requires
all
federal
agencies
to
consult
with
the
National
Marine
Fisheries
Service
(
NMFS)
for
marine
and
Page
42
of
62
andronomus
listed
species,
or
the
United
States
Fish
and
Wildlife
Services
(
FWS)
for
listed
wildlife
and
freshwater
organisms,
if
they
are
proposing
an
"
action"
that
may
affect
listed
species
or
their
designated
habitat.
Each
federal
agency
is
required
under
the
Act
to
insure
that
any
action
they
authorize,
fund,
or
carry
out
is
not
likely
to
jeopardize
the
continued
existence
of
a
listed
species
or
result
in
the
destruction
or
adverse
modification
of
designated
critical
habitat.
To
jeopardize
the
continued
existence
of
a
listed
species
means
"
to
engage
in
an
action
that
reasonably
would
be
expected,
directly
or
indirectly,
to
reduce
appreciably
the
likelihood
of
both
the
survival
and
recovery
of
a
listed
species
in
the
wild
by
reducing
the
reproduction,
numbers,
or
distribution
of
the
species."
50
C.
F.
R.
'
402.02.

To
facilitate
compliance
with
the
requirements
of
the
Endangered
Species
Act
subsection
(
a)(
2)
the
Environmental
Protection
Agency,
Office
of
Pesticide
Programs
has
established
procedures
to
evaluate
whether
a
proposed
registration
action
may
directly
or
indirectly
reduce
appreciably
the
likelihood
of
both
the
survival
and
recovery
of
a
listed
species
in
the
wild
by
reducing
the
reproduction,
numbers,
or
distribution
of
any
listed
species
(
U.
S.
EPA
2004).
After
the
Agency=
s
screening­
level
risk
assessment
is
performed,
if
any
of
the
Agency=
s
Listed
Species
LOC
Criteria
are
exceeded
for
either
direct
or
indirect
effects,
a
determination
is
made
to
identify
if
any
listed
or
candidate
species
may
co­
occur
in
the
area
of
the
proposed
pesticide
use.
If
determined
that
listed
or
candidate
species
may
be
present
in
the
proposed
use
areas,
further
biological
assessment
is
undertaken.
The
extent
to
which
listed
species
may
be
at
risk
then
determines
the
need
for
the
development
of
a
more
comprehensive
consultation
package
as
required
by
the
Endangered
Species
Act.

For
certain
use
categories,
the
Agency
assumes
there
will
be
minimal
environmental
exposure,
and
only
a
minimal
toxicity
data
set
is
required
(
Overview
of
the
Ecological
Risk
Assessment
Process
in
the
Office
of
Pesticide
Programs
U.
S.
Environmental
Protection
Agency
­
Endangered
and
Threatened
Species
Effects
Determinations,
1/
23/
04,
Appendix
A,
Section
IIB,
pg.
81).
Chemicals
in
these
categories
therefore
do
not
undergo
a
full
screening­
level
risk
assessment,
and
are
considered
to
fall
under
a
Ano
effect@
determination.
The
active
ingredient
uses
of
alkylbenzene
sulfonic
acids
and
sulfonates
fall
into
this
category
for
the
following
reasons:

1.
The
amount
that
will
actually
reach
the
environment
is
very
small
based
on
usage
data
for
down­
the­
drain
uses.
2.
Use
for
toilets
and
urinals
is
limited
(
no
home­
owner
or
residential
uses
are
registered).
3.
Breakdown
of
alkylbenzene
sulfonate
in
the
environment
and
via
sewage
treatment
is
rapid
and
well
documented
in
the
literature.

The
labeled
antimicrobial
uses
of
alkylbenzene
sulfonic
acids
and
sulfonates
are
not
expected
to
result
in
significant
environmental
exposure.
Therefore,
no
adverse
effects
(
NE)
to
listed
species
are
anticipated.
Use
of
alkylbenzene
sulfonates
as
inert
ingredients
in
agricultural
pesticide
formulations
is
not
expected
to
result
in
significant
environmental
exposure.
Therefore,
no
adverse
effects
(
NE)
to
listed
species
are
anticipated.
Page
43
of
62
10.2
Inert
Ingredient
Use
The
alkylbenzene
sulfonates
are
used
as
"
inert"
ingredients
in
agricultural
herbicide
formulations.
Preplant
incorporated
and
preemergence
herbicide
treatments
are
typically
applied
once
per
year
to
the
tilled,
minimally
tilled
or
no­
tilled
field
before
planting
or
before
crop
emergence
in
the
spring.
Spray
applications
are
primarily
via
ground
spray
boom
and
occasionally
by
aircraft
if
a
wet
spring.
Movement
of
the
alkylbenzene
sulfonates
from
the
treated
field
to
the
aquatic
environment
can
occur
at
the
time
of
application
due
to
spray
drift,
or
following
application
via
surface
water/
soil
flow
or
by
percolation
to
groundwater.
The
FIRST
model
has
predicted
a
maximum
potential
concentration
of
6.6
ppb
alkylbenzene
sulfonates
in
drinking
water
from
inert
agricultural
uses
(
memo
from
K.
Leifer,
2006).
Available
modeling
and
literature
suggest
that
these
chemicals
will
most
likely
biodegrade
rapidly
in
soil
due
to
microbial
degradation.

The
inert
agricultural
uses
of
alkylbenzene
sulfonates
are
not
expected
to
adversely
affect
avian
or
mammalian
species
on
an
acute
or
chronic
basis.
Aquatic
organisms
are
also
not
expected
to
be
adversely
affected
by
inert
alkylbenzene
sulfonates
use
acutely
or
chronically
due
to
the
low
predicted
level
of
alkylbenzene
sulfonates
in
water
by
FIRST.
A
chronic
freshwater
fish
toxicity
test
NOAEC
of
400
ug/
L
alkylbenzene
sulfonates
is
considered
protective
of
ecosystem
structure
and
function
in
experimental
streams.
Therefore,
the
predicted
concentration
of
6.6
ug/
L
in
water
is
well
below
our
chronic
Level
of
Concern
(
LOC).

11.0
DEFICIENCIES/
DATA
NEEDS
Hazard
Data
Gaps.
The
toxicology
database
for
the
alkylbenzene
sulfonates
consists
almost
entirely
of
published
literature,
is
essentially
complete
and
of
acceptable
quality
to
assess
the
potential
hazard
to
humans.

Ecological
Data
Gaps.
Valid
acute
aquatic
toxicity
studies
for
fish
and
invertebrates
must
be
submitted
to
support
indoor
use
patterns.
These
studies
are:

850.1075
­
Acute
Freshwater
Fish
using
TGAI
DDBSA
on
Rainbow
trout
or
Bluegill
sunfish
850.1010
­
Acute
Freshwater
Invertebrate
using
TGAI
DDBSA
on
Daphnia
magna
Based
on
DDBSA
task
force
data
provided,
DDBSA
typically
contains
a
range
of
carbon
chain
lengths
from
10
to
16.
Study
MRID
47025025
indicates
that
the
greater
the
number
of
carbons,
the
greater
the
toxicity
to
Daphnia
magna.
For
example,
C10
was
slightly
toxic
and
C14
was
highly
toxic.
DDBSA
TGAI
with
the
highest
carbon
length
must
be
used
in
aquatic
toxicity
tests.

Label
Hazard
Statements
for
Terrestrial
and
Aquatic
Organisms
Manufacturing
use
products
must
state:
Page
44
of
62
"
This
pesticide
is
toxic
to
fish
and
aquatic
invertebrates".

"
Do
not
discharge
effluent
containing
this
product
into
lakes,
streams,
ponds,
estuaries,
oceans,
or
other
waters
unless
in
accordance
with
the
requirements
of
a
National
Pollutant
Discharge
Elimination
System
(
NPDES)
permit
and
the
permitting
authorities
are
notified
in
writing
prior
to
discharge.
Do
not
discharge
effluent
containing
this
product
to
sewer
systems
without
previously
notifying
the
local
sewage
treatment
plant
authority.
For
guidance
contact
your
State
Water
Board
or
Regional
Office
of
the
EPA."

Residential/
Occupational
Data
Gaps.
Confirmatory
worker
exposure
data
are
necessary,
due
to
the
significant
limitations
of
the
existing
exposure
data
used
in
this
assessment.
The
Agency
is
requesting
worker
exposure
studies
that
evaluate
inhalation
(
Guideline
875.1400)
exposure
for
indoor
uses.

12.0
REFERENCES
MRID
41143901
­
Lloyd,
D.;
Grimes,
J.;
Jaber,
M.
(
1989)
Nacconol
90G:
An
Acute
Oral
Toxicity
Study
with
the
Bobwhite:
Final
Report:
Wildlife
International
Ltd.
Project
No.
257­
101.
Unpublished
study
prepared
by
Wildlife
International
Ltd.
26p.

MRID
42439803
­
Bollman,
M.
A.
et.
al.
(
1990)
Report
on
the
Algal
Toxicity
Tests
of
Selected
Office
of
Toxic
Substances
(
OTS)
Chemicals.
US
EPA
Environmental
Research
Laboratory.
179p.

MRID
44260002
­
McKim,
J.
M.;
Arthur,
J.
W.;
Thorslund,
T.
W.
(
1975)
Toxicity
of
Linear
Alkylate
Sulfonate
Detergent
to
Larvae
of
Four
Species
of
Freshwater
Fish.
USEPA,
Nat.
Water
Qual.
Lab.,
Duluth,
MN.
Bulletin
of
Environmental
Contamination
and
Toxicology.
Vol
14
(
1)
pg.
1­
7.

MRID
44260009
­
Calamari,
D.;
Marchetti,
R.
(
1973)
The
Toxicity
of
Mixtures
of
Metals
and
Surfactants
to
Rainbow
Trout
(
Salmo
gairdneri
rich.)
Water
Research.
Vol.
7(
10)
pg.
1453­
1464.

MRID
47025025
­
Maki,
A.
W.;
Bishop,
W.
E.
(
1979)
Acute
Toxicity
Studies
of
Surfactants
to
Daphnia
magna
and
Daphnia
pulex.
Archives
of
Environmental
Contamination
and
Toxicology.
Vol.
8,
p.
599­
612.
Sponsored
by
The
Proctor
and
Gamble
Company
USA,
Ivorydale
Technical
Ctr.,
Cincinnati,
OH.

Fairchild,
J.
F.,
F.
J.
Dwyer,
T.
W.
La
Point,
S.
A.
Burch,
and
C.
G.
Ingersoll.
1993.
Evaluation
of
a
Laboratory­
Generated
NOEC
For
Linear
Alkylbenzene
Sulfonate
In
Outdoor
Experimental
Streams.
Environmental
Toxicology
and
Chemistry.
Vol.
12(
10):
1763­
1775.
Symposium
on
Surfactants
and
Their
Environmental
Safety,
11th
Annual
Meeting,
Society
of
Environmental
Toxicology
and
Chemistry,
Arlington,
VA,
Nov.
11­
15,
1990.
Page
45
of
62
Human
and
Environmental
Risk
Assessment
(
HERA).
2004.
LAS
 
Linear
Alkylbenzene
Sulphonates
(
CAS
No.
68411­
30­
3)

Lewis,
M.
A.,
C.
A.
Pittinger,
D.
H.
Davidson
and
C.
J.
Ritchie.
1993.
In
Situ
Response
of
Natural
Periphyton
To
An
Anionic
Surfactant
And
An
Environmental
Risk
Assessment
For
Phytotoxic
Effects.
Environmental
Toxicology
and
Chemistry.
Vol.
12(
10):
1803­
1812.
Symposium
on
Surfactants
and
Their
Environmental
Safety,
11th
Annual
Meeting,
Society
of
Environmental
Toxicology
and
Chemistry,
Arlington,
VA,
Nov.
11­
15,
1990.

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
)
Page
46
of
62
Appendix
A
Toxicity
Profile
for
Alkylbenzene
Sulfonates
Page
47
of
62
Table
A­
1
Toxicity
Profile
of
Alkylbenzene
Sulfonates
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
(
LAS­
Na)
for
one
month
Sprague­
Dawley
Rats
(
12/
sex/
group)

Purity:
99.5%
LAS­
Na:
Body
weight
increase
was
suppressed;
feed­
efficacy
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
after
Repeated
Oral
Ingestion
in
Rats.
Industrial
Toxicology
Research
Centre,
Mahatma
Ganghi
Marg,
Lucknow
Study
No.
DDBSA
JV­
RP­
013.
Acceptable
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
F
Albino
Rat
(
9/
group)

Purity:
Not
Reported
NOEL:
<
50
mg/
kg/
d
LOEL:
50
mg/
kg/
d
based
on
alterations
of
several
enzymes
indicative
of
liver
and
kidney
damage
Page
48
of
62
Table
A­
1
Toxicity
Profile
of
Alkylbenzene
Sulfonates
Guideline
No./
Study
Type
MRID
No./
Reference
Information/
Study
Classification
Dosing
and
Animal
Information
Results
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
(
Wistar­
derived)
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.

Open
Literature
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
M
Wistar
Rat
(
5/
group)

Purity:
Not
Reported
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.

870.3100
Oral
Subchronic
(
rodent)
MRID
No.
43498413
Heywood
et
al.
(
1978)
Toxicology
Studies
of
Linear
Alkyl
Sulphonate
LAS
was
given
to
four
groups
of
three
males
and
three
females
at
doses
of
30,
150,
300
mg/
kg
bw/
day
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
Page
49
of
62
Table
A­
1
Toxicity
Profile
of
Alkylbenzene
Sulfonates
Guideline
No./
Study
Type
MRID
No./
Reference
Information/
Study
Classification
Dosing
and
Animal
Information
Results
(
LAS)
in
Rhesus
Monkeys
I.
Simultaneous
Oral
and
Subcutaneous
Administration
for
28
Days.
Toxicol.
Appl.
Pharmacol.
11:
245­
250.
(
HERA)

Acceptable
Guideline
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
(
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.
Pharmacol.,
45:
477­
496.

Acceptable
Guideline
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
(
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%
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
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
Page
50
of
62
Table
A­
1
Toxicity
Profile
of
Alkylbenzene
Sulfonates
Guideline
No./
Study
Type
MRID
No./
Reference
Information/
Study
Classification
Dosing
and
Animal
Information
Results
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.

870.3700a
Developmental
MRID
43498424
and
43498425
LAS
(
0.1
ml
)
was
applied
at
a
concentration
of
20%
Development
was
retarded
and
cleavage
of
eggs
was
interrupted.
Significantly
higher
numbers
of
embryos
Page
51
of
62
Table
A­
1
Toxicity
Profile
of
Alkylbenzene
Sulfonates
Guideline
No./
Study
Type
MRID
No./
Reference
Information/
Study
Classification
Dosing
and
Animal
Information
Results
Toxicity
(
rodent)
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
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%
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)

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
Page
52
of
62
Table
A­
1
Toxicity
Profile
of
Alkylbenzene
Sulfonates
Guideline
No./
Study
Type
MRID
No./
Reference
Information/
Study
Classification
Dosing
and
Animal
Information
Results
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
Developmental
Toxicity
Tiba
et
al.
(
1976)
Effects
of
LAS
on
Dam,
Fetus,
and
Newborn
Rat.
J.
Food
Hyg.
Soc.
Jpn.
LAS
was
administered
in
the
diet
at
doses
of
80
and
780
mg/
kg
bw/
d
from
day
0
NOAEL
(
maternal):
780
mg/
kg
bw/
d
NOAEL
(
fetuses):
780
mg/
kg
bw/
d
At
780
mg/
kg
bw/
day
there
were
no
abnormalities
in
the
body
weight
gains
of
the
dams,
or
in
the
occurrence
and
Page
53
of
62
Table
A­
1
Toxicity
Profile
of
Alkylbenzene
Sulfonates
Guideline
No./
Study
Type
MRID
No./
Reference
Information/
Study
Classification
Dosing
and
Animal
Information
Results
(
rodent)
(
Shokuhin
Eiseigaku
Zassh)
17(
1):
66­
71.
(
HERA)

Open
Literature
to
20
of
gestation
F
Rat
(
16/
dose)

Purity:
Not
Reported
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.
LAS
were
applied
to
the
dorsal
skin
of
rats
three
times
per
week
at
doses
of
Treatment
had
no
effect
on
organ
weights
or
histopathological
appearance,
and
there
was
no
evidence
of
toxicity
or
carcinogenicity.
Page
54
of
62
Table
A­
1
Toxicity
Profile
of
Alkylbenzene
Sulfonates
Guideline
No./
Study
Type
MRID
No./
Reference
Information/
Study
Classification
Dosing
and
Animal
Information
Results
(
rodent)
Tokyo,
Science
and
Technology
Agency,
Research
and
Coordination
Bureau,
pp.
18­
54.
(
WHO
1996)

Open
Literature
1,
5,
or
25
mg/
rat
for
24
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,
K­
ATPase.

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)
Page
55
of
62
Table
A­
1
Toxicity
Profile
of
Alkylbenzene
Sulfonates
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
Oxid
e
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
Oxid
e
with
Alkylbenzenesulfonate
on
Gastric
Carcinogenesis
in
Rats.
GANN:
61,
27­
33.

Acceptable
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
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.
Page
56
of
62
Table
A­
1
Toxicity
Profile
of
Alkylbenzene
Sulfonates
Guideline
No./
Study
Type
MRID
No./
Reference
Information/
Study
Classification
Dosing
and
Animal
Information
Results
Guideline
18
weeks
64
M
Motoyama
Strain
Rat
Purity:
Not
Reported
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
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
N­
N
itrosoguanidine
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.
SDDBS
was
tested
at
cytotoxic
levels
or
limit
concentrations
of
2,000­
30,000
ug/
plate
for
2
days
(
Salmonella)
or
8
days
(
SHE)
Negative
(
both
with
and
without
S­
9
metabolic
activation)
Page
57
of
62
Table
A­
1
Toxicity
Profile
of
Alkylbenzene
Sulfonates
Guideline
No./
Study
Type
MRID
No./
Reference
Information/
Study
Classification
Dosing
and
Animal
Information
Results
Cosmet.
Toxicol
18:
289­
296.
(
HERA)

Acceptable
Guideline
Strain:
Salmonella
typhimurium
­
TA
98
and
TA
100
cells
and
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.
There
was
no
significant
difference
between
any
of
the
groups
given
LAS
and
the
negative
control
group
in
the
incidence
of
chromosomal
aberrations
Page
58
of
62
Table
A­
1
Toxicity
Profile
of
Alkylbenzene
Sulfonates
Guideline
No./
Study
Type
MRID
No./
Reference
Information/
Study
Classification
Dosing
and
Animal
Information
Results
M
ICR:
JCL
Mouse
Purity:
Not
Reported
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
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
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.
Page
59
of
62
Table
A­
1
Toxicity
Profile
of
Alkylbenzene
Sulfonates
Guideline
No./
Study
Type
MRID
No./
Reference
Information/
Study
Classification
Dosing
and
Animal
Information
Results
Alkylbenzene
Sulfonate
(
LAS)
in
Mice
and
Rats.
Ann
Rep
Tokyo
Metrop
Res
Lab
Public
Heath,
27(
2):
100­
104.

(
HERA)

Open
Literature
became
pregnant.
The
pregnant
mice
were
laparotomized
on
day
13
of
gestation
7
M
ICR:
JCL
Mice
Purity:
Not
Reported
Metabolism
870.7485
General
Metabolism
MRID
43498410
Creswell
et
al.
(
1978)
Toxicology
Studies
of
Linear
Alkylbenzene
Sulphonate
(
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
para­
dodecylbenze
nesulfonate
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
Repeated
doses
of
(
14)
C­
labeled
alkylbenzenesulfonate
were
orally
administered
Radioactivity
did
not
accumulate
in
the
tissues
Page
60
of
62
Table
A­
1
Toxicity
Profile
of
Alkylbenzene
Sulfonates
Guideline
No./
Study
Type
MRID
No./
Reference
Information/
Study
Classification
Dosing
and
Animal
Information
Results
Review
of
the
Literature
Published
during
1978
and
1979.
London:
The
Royal
Society
of
Chemistry,
p.
354.
Rhesus
Monkey
Purity:
Not
Reported
870.7485
General
Metabolism
MRID
43498431
W.
Michael
(
1968)
Metabolism
of
Linear
Alkylate
Sulfonate
and
Alkyl
Benzene
Sulfonate.
Toxicol.
Appl.
Pharmacol.
12:
473­
485.

Acceptable
Guideline
LAS­
S35
was
administered
orally
to
fasted
rats
at
doses
of
0.6,
1.2,
8,
and
40
mg
Charles
River
CD
M
Rat
Purity:
Not
Reported
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.

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
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
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
Page
61
of
62
Table
A­
1
Toxicity
Profile
of
Alkylbenzene
Sulfonates
Guideline
No./
Study
Type
MRID
No./
Reference
Information/
Study
Classification
Dosing
and
Animal
Information
Results
Ameliorating
Effects
of
Dietary
Fiber
in
the
Rat.
J.
Nutrit.
Science
and
Science
and
Vitaminology,
28:
483­
489.

Kimura
et
al.
(
1982)
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
were
collected
in
30
minute
aliqouts
for
120
minutes
M
Wistar
Rat
Purity:
0.5%

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):
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
Haemolysis
occurred
at
concentrations
>=
5
mg/
litre.
Page
62
of
62
Table
A­
1
Toxicity
Profile
of
Alkylbenzene
Sulfonates
Guideline
No./
Study
Type
MRID
No./
Reference
Information/
Study
Classification
Dosing
and
Animal
Information
Results
859­
864.
(
EHC
169)

Open
Literature
Rabbit
Red
Blood
Cell
Purity:
Not
Reported
