
1
of
18
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
Date:
March
29,
2006
MEMORANDUM
SUBJECT:
Response
to
Error
Comments
on
the
Alkylbenzene
Sulfonates
(
ABS)
Preliminary
Risk
Assessment.
PC
Code:
079010,
190116
and
098002.
Case
No.
4006.
DP
Barcode:
323960
FROM:
Deborah
Smegal,
MPH,
Toxicologist/
Risk
Assessor
Ayaad
Assaad,
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)
2
of
18
Comments
from
Microcide
®
,
Inc.
Dated
February
26,
2006.

Comment
1a.
The
use
of
sodium
dodecylbenzene
sulfonate
(
CAS
#
25155­
30­
0)
has
6.54%
less
dodecylbenzene
sulfonic
acid
(
CAS
#
27176­
87­
0
and
CAS
#
68584­
22­
5).
This
needs
to
be
compensated
in
calculating
levels
of
inhalation
and/
or
contact
risk
posed
by
the
active
moiety
of
SDBS,
since
under
acidic
condition
the
acid
form
rather
than
the
salt
form
is
present.
The
calculations
are
as
follows:
(
Sodium
dodecylbenzene
sulfonate
mol
wt:
348.59
and
sodium
mol
wt
23).
Therefore,
the
percent
of
dodecylbenzene
sulfonic
acid
=
348.49­
23=(
325.49/
348.49)
x
100=
93.4%
in
acidic
products.

Response:
The
assessment
reflects
all
three
registered
chemicals,
and
thus
the
Agency
does
not
believe
that
this
adjustment
is
necessary.

Comment
1b
(
This
is
also
listed
as
Comment
1
on
registrant
submission).
The
percentage
of
alkylbenzene
sulfonates
in
various
products
can
range
from
0.036%
to
25.6%.
The
endpoint
used
in
this
document
was
developed
from
a
study
that
only
used
13%
active
ingredient.
(
Inhalation
study
NOAEL=
1
mg/
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
from
page
4:
Table
1
Residential
Inert
Assessment.

For
the
dose
calculations,
the
default
inhalation
absorption
rate
was
100%.
Therefore,
the
statement
that
"
The
values
presented
in
this
assessment
are
considered
to
be
underestimations
of
the
potential
risks
that
arise
from
exposure
to
alkylbenzene
sulfonates"
appears
to
be
general
"
one
size
fits
all"
type
statement
and
be
not
applied
to
products
which
have
significantly
lower
use
concentration
of
the
active
ingredient.

Response:
The
Agency
has
removed
the
statement
"
The
values
in
this
assessment
are
considered
to
be
underestimations
of
the
potential
risks
that
arise
from
exposure
to
alkylbenzene
sulfonate."

Comment
2.
Since
"
Quantification
of
dermal
risk
is
not
required
because:
1)
the
alkylbenzene
sulfonates
are
surfactants
that
are
dermal
irritants
at
concentrations
generally
greater
than
20%
solution
and
2)
no
systemic
toxicity
was
seen
following
repeated
dermal
applications
to
rabbits
at
200
mg/
kg/
day
(
with
an
end
use
product),
and
3)
no
developmental
toxicity
concerns
were
seen
following
repeated
dermal
applications
to
pregnant
mice,
rats
or
rabbits."

Therefore,
the
ready
to
use
product
Reg
#
71094­
2
with
only
0.036%
active
ingredient
has
been
determined
to
be
toxicologically
safe
by
dermal
and
inhalation
studies
and
do
not
warrant
respective
dermal
handling
labels
as
suggested
in
the
report.

Response.
The
Agency
has
estimated
risks
of
concern
for
both
71094­
1
and
71094­
2
products
as
shown
on
Table
8
of
the
"
Occupational
and
Residential
Exposure
Assessment
of
Alkylbenzene
Sulfonates
for
the
Reregistration
Eligibility
Decision
Document".
The
3
of
18
total
inhalation
MOE
is
90
for
cleaning
and
sanitizing
with
the
same
product
71094­
2
using
the
sponge/
mesh/
wiping
and
immersion/
flooding
methods,
and
also
inhalation
for
product
71094­
1,
there
are
inhalation
risks
of
concern
of
93
and
90
for
wiping
and
immersion/
flooding
or
wiping
and
low
pressure
spray.

Comment
3.
Toxicity
of
sodium
dodecylbenzene
sulfonate
(
EPA
DATA).
No
adverse
observed
effect
level
(
NOAEL).
Chronic
dietary=
50
mg/
kg/
day
lowest
observed
adverse
effect
level
(
LOAEL)=
114­
350
mg/
kg/
day.

Inhalation
study
shows
that
NOAEL
=
1
mg/
m3
=
equivalent
to
approximately
0.14
mg/
kg/
day
of
13%
active
ingredient.
This
means
that
the
average
70
kg
person
will
have
no
effect
at
0.14
x
70=
9.8
mg
of
ai/
day.
Thus
if
the
concentration
of
active
ingredient
is
lower
than
13%
the
inhalation
potential
will
be
proportionately
lower.
Thus
with
0.036%
concentration
the
inhalation
potential
will
be
0.14
x
(
0.036/
13)=
0.00038
mg/
kg/
day
for
use
solutions
of
Reg
#
71094­
1
and
Reg
#
71094­
2.
Even
if
the
use
level
is
calculated
for
both
cleaning
and
sanitizing
which
comes
to
about
(
0.00038
x
2
cleaning
+
0.00038
sanitizing)
=
0.0011
mg/
kg/
day.
This
is
lower
than
the
inhalation
NOAEL
of
0.14
mg/
kg/
day.

Note:
when
cleaning
concentration
is
higher
and
the
sanitizing
concentration
is
lower,
the
higher
cleaning
concentration
is
diluted
by
subsequent
use
of
the
lower
sanitizing
concentration.
The
effect
is
not
additive
and
the
lower
concentration
should
be
used
for
any
residual
calculations.

Response:
The
Agency
risk
estimates
account
for
the
amount
of
active
ingredient
in
the
registered
products,
and
this
is
reflected
in
the
Margin
of
Exposure
(
MOE)
values
presented
on
Tables
7
and
8
of
the
risk
assessment.
The
inhalation
endpoint
is
based
on
a
NOAEL
of
1
mg/
m3
for
detergent
that
contains
13%
C12
linear
alkylbenzene
sulfonate.
The
Agency
disagrees
with
the
calculations
presented
by
the
commentor.

Comment
4.
There
are
certain
anomalies
in
Table
8.
Two
products
Reg
#
71094­
1
and
Reg
#
71094­
2
with
the
same
use
level
of
0.036%
sodium
dodecylbenzene
sulfonate
show
different
inhalation
MOE
values.

Response:
The
Agency
disagrees
with
this
comment.
The
Agency
records
show
that
the
Reg
#
71094­
2
contains
0.036%
as
a
ready
to
use
product
(
0.003
lb
ai/
gal),
while
Reg#
71094­
1
contains
3.6%
as
a
water
soluble
packet
(
there
are
two
application
rates
of
0.00603
or
0.00302
lb
ai/
gal,
since
the
cleaning
and
sanitizing
steps
on
the
label
recommend
two
different
dilutions).
4
of
18
Comments
from
Scientific
&
Regulatory
Consultants,
Inc.
on
behalf
of
Chemical
Systems
of
Florida,
Dated
March
6,
2006.

The
SRC
Scientific
and
Regulatory
Consultants,
Inc.
comments
are
in
relation
to
the
Agency
review
on
the
fruit
and
vegetable
wash
for
these
chemicals.
The
letter
points
out
that:

1)
The
label
for
Reg.
#
71695­
1
allows
a
fruit
and
vegetable
wash
with
a
solution
made
by
mixing
1
ounce
of
CS
100
Sanitizer
to
5
gallons
of
water.
The
label
further
instructs
a
user
to
never
exceed
a
rate
of
2
ounces
of
CS­
100
to
5
gallons
of
water.
In
either
instance
a
potable
water
rinse
is
required.

The
letter
goes
on
to
state:
"
To
determine
the
level
of
DDBSA
in
these
solutions
you
must
first
consider
the
dilution
rate
and
the
amount
of
DDBSA
in
CS­
100
Acid
which
is
17.46%.
Therefore
the
maximum
amount
of
DDBSA
in
a
2
oz
to
5
gallon
dilution
of
CS­
100
Acid
is
determined
as
follows:

2
oz/
5
gal
x
gal/
128
oz
x
17.46%
DDBSA
=
0.0546%
DDBSA
The
dietary
risk
assessment
document
asserts
that
the
solution
will
contain
0.31%
DDBSA.
Instead
the
solution
contains
0.31%
CS­
100
Acid
Sanitizer.
Based
on
the
label
declaration
of
17.46%
DDBSA,
the
solution
contains
0.0546%
DDBSA.
This
is
well
below
the
0.2%
level
permitted
in
21
CFR
173.315
without
a
potable
water
rinse.

Further,
using
the
maximum
DDBSA
level
of
0.0546
in
the
residue
calculation
on
page
8,
the
potential
residue
(
without
rinsing)
from
CS­
100
Acid
Sanitizer
is
11.6
ppm.
Using
EPA's
assumptions,
this
number
was
determined
as
noted
below.

0.023
g/
cm2
x
12.56
cm2
x
0.000546
(
0.0546%)
DDBSA
=
0.000158
g
or
0.0158
mg
DDBSA
0.0158
mg
DDBSA/
0.00136
kg
blueberries
=
11.6
mg/
kg
or
ppm
When
correctly
calculated,
the
labeled
use
rate
for
CS­
100
Acid
Sanitizer
presents
an
acceptable
dietary
risk.
We
estimate
that
for
children,
which
was
noted
as
a
concern,
the
cPAD
for
1­
2
year
olds
is
89.5
and
64.6
for
3­
5
years
old.

Based
on
this
calculation
we
believe
that
this
may
obviate
the
need
to
conduct
any
further
dietary
risk
assessments."
5
of
18
EPA
Response
to
the
SRC
comments:

1.
The
SRC
calculations
assume
that
the
0.2%
number
in
the
CFR
173.315
Regulation
refers
to
the
percentage
of
formulation
used
in
the
fruit
and
vegetable
wash.

We
have
assumed
that
the
0.2%
stated
in
the
Regulation
refers
to
the
%
of
active
ingredient
used
in
the
wash
solution.

The
21
CFR
173.315
Regulation
reads:

§
173.315
Chemicals
used
in
washing
or
to
assist
in
the
peeling
of
fruits
and
vegetables.

Under
(
a)(
2)
the
Regulation
reads:
"
Substances
identified
in
this
subparagraph
and
subject
to
such
limitations
as
are
provided:"

Further,
under
(
a)(
2)
the
Regulation
reads:
"
Sodium
dodecylbenzene­
sulfonate
(
alkyl
group
predominantly
C12
and
not
less
than
95%
C10
to
C16).

The
Regulation
does
not
indicate
that
the
percentages
stated
are
for
the
formulation;
instead
the
Regulation
uses
the
words,
"
Chemical"
and
"
Substance".
Consequently
we
have
considered
the
0.2%
"
Limitations"
refers
to
the
active
chemical
ingredient
and
not
to
the
percent
formulation
in
the
wash
solution.

Also,
if
the
Regulation
refers
to
the
percentage
formulation
in
the
wash
solution,
there
could
be
a
wide
range
of
%
active
ingredient
in
the
wash
solutions
that
are
made
up.

We
will
continue
to
consider
that
the
0.2%
use
solution
in
21
CFR
173.315
refers
to
the
percentage
active
ingredient
in
the
wash
solution.
We
will
revise
our
calculations
if
the
registrant(
s)
can
provide
written
confirmation
from
the
Food
&
Drug
Administration
that
the
0.2%
in
the
Regulation
refers
to
the
percentage
of
formulation
in
the
wash
solution.
The
Regulation,
as
written,
appears
to
refer
to
percent
active
ingredient
in
the
wash
solution.

Using
the
assumption
that
the
0.2%
refers
to
percent
formulation
in
the
wash
solution,
the
registrant(
s)
have
calculated
an
acceptable
dietary
risk.

The
SRC
letter
also
refers
to
the
labeling
that
bears
a
potable
water
rinse
after
the
fruit
and
vegetable
wash.
We
acknowledge
that
a
potable
water
rinse
after
treatment
will
remove
a
portion
of
the
residue
after
the
wash
treatment.
However,
there
are
no
residue
data
to
show
the
reduction
in
residue
level
that
would
occur
from
the
potable
water
rinse.
The
reduction
in
residue
level
that
would
occur
after
a
potable
water
rinse
would
vary
widely
between
various
commodities
such
as
e.
g.
apples,
peaches,
strawberries,
broccoli
and
lettuce.
In
the
absence
of
residue
data
to
show
residue
reduction
resulting
from
a
potable
water
rinse,
we
cannot
make
a
prediction
on
the
percentage
residue
reduction
that
6
of
18
will
occur.

Further
EPA/
AD/
RASSB
Considerations:

AD
has
considered
the
use
of
blueberries
as
a
conservative
approach
to
the
calculation
of
dietary
risk
for
the
fruit
and
vegetable
wash.
Considering
the
wide
range
of
commodities
that
can
be
washed
and
on
their
different
morphologies,
the
use
of
blueberries
is
very
conservative.

We
have
slightly
revised
the
commodity
selection
and
instead
of
using
blueberries
as
a
representative
crop
for
all
fruits
and
vegetables,
we
have
decided
to
use
Concord
grapes.

Using
Concord
grapes,
we
have
revised
our
dietary
risk
calculations.
This
revision
will
be
reflected
in
and
updated
version
of
the
preliminary
dietary
risk
assessment.
Our
calculations
follow.

FRUIT
AND
VEGETABLE
WASH
The
label,
CS­
100
Acid
Anionic
Sanitizer,
EPA
Reg.
#
71695­
1,
bears
a
use
for
washing
fruits
and
vegetables.

The
FDA
Regulation,
21
CFR
173.315,
permits
this
use
provided
that
the
wash
solution
does
not
contain
dodecylbenzene
sulfonic
acid
at
a
level
greater
than
0.2%.
No
potable
water
rinse
is
required
by
the
Regulation.
We
presume
that
the
use
limitation
is
for
the
parent
chemical
because
the
Regulation
makes
no
mention
of
formulations.
The
use
limitation
states,
"
Not
to
exceed
0.2%
in
wash
water.
May
be
used
in
washing
or
to
assist
in
the
lye
peeling
of
fruits
and
vegetables".
Note:
If
the
use
limitation
were
intended
to
apply
to
a
formulation,
there
would
be
a
broad
range
of
application
rates
depending
on
the
concentration
of
the
chemical
in
the
formulation.

The
label
bears
a
use
that
provides
for
a
fruit
and
vegetable
wash
with
a
solution
containing
0.16
%
dodecylbenzene
sulfonic
acid,
without
a
potable
water
rinse.

The
label
also
bears
a
use
a
use
that
provides
for
a
fruit
and
vegetable
wash
with
a
solution
containing
0.31%
dodecylbenzene
sulfonic
acid,
with
a
potable
water
rinse.

There
are
no
data
to
show
that
the
level
of
residues
on
fruits
and
vegetables
would
be
reduced
to
the
level
that
would
have
occurred
from
a
0.2%
wash.
However,
AD
concludes
that
dodecylbenzene
sulfonic
acid
residues
would
be
significantly
reduced
by
the
potable
water
rinse
and
would
be
less
than
residues
resulting
from
the
0.2%
wash.

There
are
no
residue
data
to
show
the
level
of
dodecylbenzene
sulfonic
acid
that
will
result
on
fruits
and
vegetables
from
the
0.2%
wash
solution
with
a
potable
water
rinse.
Lacking
residue
data
to
show
the
level
of
residues
expected
on
fruits
and
vegetables,
we
have
calculated
the
level
of
residues
on
fruits
and
vegetables
using
the
following
model.
7
of
18
Dodecylbenzene
sulfonate
Fruit
and
Vegetable
Wash
Dietary
Residue
Calculations:

Calculation
for
percent
dodecylbenzene
sulfonate
in
the
wash
water:

The
maximum
use
rate
is
2000
ppm
of
dodecylbenzene
sulfonate
(
0.2%
x
10,000)
for
fruit
and
vegetables.

We
will
use
the
surface
area
and
weight
of
Thompson
Seedless
grapes
to
calculate
residues
in
fruits
and
vegetables.
This
is
a
small
grape
which
accounts
for
half
of
the
table
grapes
grown
in
California
and
is
used
to
make
over
90%
of
the
grapes
grown
in
the
United
States.
We
are
not
using
a
larger
fruit
or
vegetable
in
our
modeling
because
there
are
commodities
that
have
large
surface
area­
weight
relationships.
The
use
of
grapes
in
our
model
appears
to
provide
a
reasonable
worst
case
situation
for
residues
in
fruits
and
vegetables.

Grape
specifications:
Diameter
of
one
grape
=
16
mm
(
Source:
University
of
California
Cooperative
Extension,
Tulare
County
http://
cetulare.
ucdavis.
edu/
pubgrape/
tb195.
htm
Mass
of
one
grape
=
4.0
gm
or
0.0040
kg
(
Source:
University
of
California
Cooperative
Extension,
Tulare
County
http://
cetulare.
ucdavis.
edu/
pubgrape/
tb195.
htm
)

Surface
area
of
one
grape
=
15.88
cm2
Based
on
surface
area
of
a
sphere
where
A
=
4 r2
(
where
r
=
8
mm)
A
=
4
x
3.14
x
(
8
mm)
2
A
=
803.8
mm2
A
=
8.04
cm2
Amount
of
Residue
on
Grapes:
Assume
the
film
thickness
of
the
solution
on
the
surface
of
the
berry
is
0.0023
g/
cm2
(
Source:
Proctor
and
Gamble
exposure
assessment
for
ingestion
of
dishwashing
product
residues
­
based
on
the
amt
of
rinse
water
in
contact
with
dishware
surfaces
http://
www.
scienceinthebox.
com/
en_
UK/
safety/
ingestionfromsurface_
en.
html)

0.0023
g/
cm2
x
8.04
cm2
x
0.002
(
0.2%)
dodecylbenzene
sulfonate
=
0.0000369
gm
or
0.037
mg
dodecylbenzenesulfonate
0.037
mg
dodecylbenzene
sulfonate/
0.004
kg
grape
=
9.25
mg/
kg
or
ppm
DIETARY
EXPOSURE
ASSESSMENT
FOR
THE
FRUIT
AND
VEGETABLE
WASH
8
of
18
This
part
of
the
non­
cancer
dietary
risk
assessment
was
carried
out
by
Cassi
Walls
(
RASSB/
AD).
It
was
conducted
using
the
Dietary
Exposure
Evaluation
Model
(
DEEMFDIC
 
)
,
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%
crop
treatment)
and
uses
the
deterministic
approach.
As
input
parameters
for
modeling
analyses,
the
level
of
9.25
ppm
was
used
based
on
the
modeling
discussed
above.

Dietary
Risk
for
Fruit
and
Vegetable
Wash
USE
DAILY
DIETARY
DOSE
(
mg/
kg
bw/
day)
%
aPAD
%
cPAD
Fruit
and
Vegetable
Wash
0.0979
(
U.
S.
Pop.)
0.2793
(
child
1­
6)
0.3558
(
child
1­
2)
0.2573
(
child
3­
5)
No
Effects
No
Effects
No
Effects
No
Effects
19.6%
55.9%
71.2%
51.5%

Dietary
risks
were
calculated
in
the
above
table
for
the
U.
S.
general
population
and
for
those
groups
exposed
to
the
highest
risk.
The
chronic
analyses
were
below
the
Agency's
level
of
concern
for
all
of
the
Population
Subgroups
using
the
Agency
DEEM.
The
most
highly
exposed
group
was
children
1­
2
years
old
with
71.2%
of
the
cPAD).

These
residue
calculations
provide
an
acceptable
dietary
risk
of
concern
for
population
subgroups
for
this
chemical.
9
of
18
Commenter
Name:
DDBSA
Joint
Venture
Error
Only
Comments:
DDBSA
DRAFT
Preliminary
Risk
Assessment
[
NOTE:
Comments
in
Tables
2­
7
(
individual
reports)
are
not
repeated
in
Table
1
(
Preliminary
Risk
Assessment)
when
the
data
from
the
individual
reports
have
been
directly
transferred
to
the
Preliminary
Risk
Assessment
(
i.
e.
the
comments
on
the
individual
reports
apply
to
the
Preliminary
Risk
Assessment
as
well)]

Table
1:
Preliminary
Risk
Assessment
Header
Page
#,
Paragraph
Comments
EPA
Response
1.0
Page
4,
Para
2
The
first
sentence
should
read
" 
there
are
currently
in
twenty­
three
products
used
 "
This
change
was
made.

Page
4,
Para
2
The
listing
of
the
concentrations
of
a.
i.
in
products
should
more
clearly
state
that
these
are
not
all
"
use
concentrations"
This
is
not
an
error.
In
estimating
exposure
and
risk,
the
Agency
considered
the
use
directions
of
the
product
labels
that
account
for
dilution
to
evaluate
the
resulting
use
concentrations.
1.0
 
Hazard
Page
4,
Para
1
and
elsewhere
According
to
the
Soap
and
Detergent
Association
review
of
data
for
linear
alkylbenzene
sulfonates
(
including
DDBSA)
for
the
High
Production
Volume
Chemical
Challenge
submission,
these
chemicals
are
not
skin
sensitizers;
it
is
not
clear
why
the
Agency
has
so
listed.
There
are
reports
of
animal
and
human
testing
in
the
literature
that
are
negative.
Further,
based
on
the
extensive
use
of
DDBSA
in
laundry
and
dish
detergents,
it
is
highly
unlikely
that
DDBSA
could
be
a
"
weak­
moderate
skin
sensitizer"
as
there
would
be
extensive
reports
of
such
findings.
The
Agency
has
provided
the
citation
that
supports
the
"
weak­
moderate
skin
sensitizer"
classification.

Nusair
TL,
PJ
Danneman,
J
Stotte,
PHS
Bay
(
1988)
Consumer
Products:
Risk
Assessment
Process
for
Contact
Sensitization,
Toxicologist
8:
258.
This
study
conducted
two
experiments
in
guinea
Pigs.
In
the
first
experiment,
they
applied
a
paste
of
LAS
to
the
skin
of
guinea
pigs
at
induction
at
concentrations
of
2­
100%
and
then
challenged
them
at
concentrations
of
1­
2%.

In
the
second
experiment,
a
prototype
liquid
laundry
detergent
(
10%
LAS)
was
applied
to
the
skin
of
guinea
pigs,
and
induced
sensitization
at
a
challenge
concentration
of
1%
(
0.1%
as
LAS).
From
both
experiments,
They
concluded
that
LAS
is
weak
to
moderate
sensitizer
(
Toxicity
Category
III).
10
of
18
Table
1:
Preliminary
Risk
Assessment
Header
Page
#,
Paragraph
Comments
EPA
Response
In
addition,
there
was
evidence
of
sensitization
in
the
monkey
inhalation
study,
which
supports
the
Agency's
classification.
1.0
 
Dermal
Exposure
Page
5
The
second
sentence
under
(
1)
needs
to
be
rewritten:
"
will
determine
and
be
used."
This
change
was
made.

1.0
 
Inhalation
Exposure
Page
5
and
elsewhere
The
NOAEL
set
by
the
Agency
from
the
dust
study
with
monkeys
is
very
conservative.
The
body
weight
effects
at
10
mg/
m3
are
reasonably
concluded
to
be
the
result
of
the
irritation
in
the
lungs
(
i.
e.
stress).
The
manuscript
states
that
the
dust
was
dried
and
"
micronized"
to
make
it
respirable.
Without
such
treatment,
the
majority
of
the
dust
from
detergents
is
not
likely
to
be
respirable.
The
authors
of
the
study
concluded
that
lesions
in
the
lungs
were
the
result
of
irritation
of
the
dust.
These
lesions
likely
result
from
the
other
components
of
the
detergent
and
the
enzyme.
The
detergent
was
also
composed
of
sodium
tripolyphosphate,
sodium
sulfate,
and
sodium
silicate
all
of
which
may
be
irritating
to
the
lungs.
The
TLV­
STEL
for
the
enzymes
(
subtilopeptidases)
in
their
crystalline
form
is
0.00006
mg/
m3
or
150­
fold
lower
than
the
concentration
in
the
LOAEL
concentration
(
10
mg/
m3
+
0.01
mg/
m3
enzyme).

Further,
the
calculated
exposure
value
of
0.14
mg/
kg/
day
is
well
below
the
oral
exposure
NOAEL
of
50
mg/
kg/
day
which,
itself,
is
very
conservative
[
based
on
minimal
effects
at
doses
more
than
2X
higher].
This
is
not
an
error
comment.
The
text
was
modified
to
state
that
the
dust
was
dried
and
"
micronized"
to
make
it
respirable,
and
to
present
the
composition
of
the
detergent.

However,
it
should
be
noted
that
most
uses
of
this
detergent
are
in
liquid
form.
It
is
a
common
misconception
that
the
small
particle
size
used
in
an
animal/
rodent
study
(
MMAD
of
1­
3
um
in
acute
studies,
1­
4
um
in
multiple
exposure
studies)
has
no
relevance
to
the
large
particle
size
that
comes
from
medium
to
coarse
powdered
material,
or
a
liquid­
powder
mix
during
use.
Detergents
are
typically
mixed
with
large
quantities
of
water
before
use.
When
the
aqueous
mix
is
used,
droplets
rapidly
shrink
as
they
fall
due
to
water
evaporation.
The
degree
of
shrinkage
depends
on
temperature,
relative
humidity,
particle
size,
and
the
length
of
time
that
the
droplets
are
suspended
in
the
air.
Since
humans
are
capable
of
inhaling
particles
>
100
um,
it
is
reasonable
to
expect
a
significant
portion
of
these
particles
to
be
inhaled.
While
most
large
particles
are
captured
in
the
nose,
some
are
capable
of
reaching
the
lungs.
Large
particles
have
the
potential
to
do
considerable
local
damage
if
they
are
respirable
because
of
the
volume
of
material
they
contain.

Furthermore,
the
Agency
inhalation
guidelines
recommend
testing
in
rats.
Rats
have
tortuous
nasal
turbinates
that
are
extremely
efficient
at
removing
particles
from
inhaled
air,
hence
most
particles
larger
than
1­
2
um
are
captured
in
the
rodent
nose.
11
of
18
Table
1:
Preliminary
Risk
Assessment
Header
Page
#,
Paragraph
Comments
EPA
Response
By
contrast,
human
noses
are
far
less
efficient
at
removing
particles.
Rats
are
also
obligate
nose
breathers
while
humans
are
not,
so
whatever
protection
the
nose
provides
is
bypassed
when
humans
breathe
through
their
mouths.

It
is
not
surprising
to
see
a
NOAEL
from
an
inhalation
study
that's
much
lower
than
a
NOAEL
from
a
feeding
study
for
the
same
chemical
for
the
following
reasons:

By
Inhalation
Route:
1.
The
lung
has
a
large
surface
area
 
>
100
m2,
which
makes
absorption
rapid
and
efficient.
2.
The
lung
receives
100%
of
the
cardiac
output.
3.
The
alveolar­
capillary
membrane
that
separates
blood
from
air
is
very
thin
(
0.5
um).
4.
Rapid
blood
passage
through
lung
capillaries
(
0.75
sec),
which
enhances
absorption
and
toxicity.

By
Oral
Route:
1.
Alteration
of
toxic
chemicals
by
stomach
acid
occurs.
2.
Absorption
is
slow
through
the
gastro­
intestinal
tract.
3.
Cardiac
output
to
GI
tract
is
only
21%,
about
1/
5
of
that
to
the
lung.
4.
Portal
circulation
is
considered
the
first
pass
of
toxic
chemicals
through
the
liver,
which
is
responsible
for
detoxification
of
the
chemical.
Risk
from
fruit
and
vegetable
wash
Page
6
and
elsewhere
Please
note
that
the
DDBSA
Joint
Venture
does
not
support
this
use
and
none
of
its
Member
Companies
have
this
use
on
their
labels.
There
are
labels
that
support
this
use
and
need
to
be
included
in
the
assessment.

Occupational
Exposure
and
Risk
Page
9,
Table
13
on
p.
36
and
elsewhere
The
Joint
Venture
believes
that
most
of
the
scenarios
presenting
MOEs
<
100
have
highly
exaggerated
exposure
estimates.
In
many
cases,
e.
g.
CIP,
there
is
virtually
no
human
exposure
to
the
full
volume
of
solution
so
the
assumption
of
exposure
to
10,000
gallons
is
This
is
not
an
error
comment,
but
an
opinion
and
includes
additional
information
regarding
the
scenarios
assessed.
The
Agency
asks
that
the
registrants
to
provide
details
(
description,
quantities
handled,
etc)
about
the
different
activities,
such
as
CIP
(
Cleaning
in
Place)
so
that
the
12
of
18
Table
1:
Preliminary
Risk
Assessment
Header
Page
#,
Paragraph
Comments
EPA
Response
unrealistic.
The
concentrate
is
typically
hooked
up
directly
to
the
system
which
prepares
the
usedilution
automatically
and
is
then
automatically
circulated
through
the
plant.
Some
operations
are
vented
(
large
tanks)
but
workers
are
usually
not
in
the
area
during
these
operations.
For
large
volume
cleaning,
the
disinfectant
is
usually
sprayed
on
the
surfaces
after
cleaning.

In
the
"
shower
stall"
scenario,
the
concentration
used
appears
to
be
approximately
18%
DDBSA.
The
label
for
EPA
Reg
#
71094­
1
(
not
a
Joint
Venture
Member
Company
Label)
indicates
a
use
concentration
of
2%
product
containing
3.6%
DDBSA
or
a
concentration
of
only
720
ppm
(
0.072%).

For
toilet
bowl
cleaning,
the
volume
used
is
much
larger
than
that
used
in
reality.

For
wiping,
the
volume
used
is
excessive
(
up
to
16
gallons/
day).
assessment
can
be
further
refined.

The
label,
#
71094­
1
does
not
have
shower
stall
listed
as
a
use
site
and
is
correctly
referenced
in
the
Occupational
and
Residential
(
ORE)
Chapter
to
have
3.6%
DDBSA.
Likewise
the
label
that
does
have
a
shower
stall
application,
the
registration
number
is,
3635­
279
and
the
%
value
of
sulfonate
in
this
product
is
only
15.52%.
(
see
Table
5
in
the
ORE
chapter)

For
both
the
toilet
bowl
cleaning
and
the
wiping,
the
quantity
handled
that
was
used
was
0.26
gallons
(
which
is
1
liter).
The
Agency
does
not
believe
that
this
value
is
excessive.
See
Section
5.1
and
Table
7
of
the
ORE
chapter.

Table
1
Page
12
The
molecular
weight
listed
for
Benzene
Sulfonic
Acid,
C10­
C16­
alkyl
derivatives
is
for
the
C10
alkyl
moiety.
It
would
be
more
appropriate
to
provide
a
M.
W.
for
the
average
chain
length.
No
change.
The
molecular
weight
of
298.44
represents
the
mass
of
C16
moiety
and
not
C10
moiety
(
16
x
12
+
1
x
26
+
16
x
3
+
1
x
32)=
C16H26O3S
=
298.44
3.0
Environmental
Fate
Page
13,
Para
5,
Last
sentence
The
statement
that
low
vapor
pressure
indicates
"
this
chemical
is
likely
to
vaporize
[
presumably
meaning
evaporate]
easily"
is
contradictive.
No
volatilization
of
DDBSA
would
be
expected
based
on
the
very
low
vapor
pressure.
The
Agency
agrees,
and
any
references
to
vaporization
has
been
corrected
to
say,
"
not
likely
to
be
volatile."

Page
16,
Para
4,
last
sentence
"
parental"
should
be
"
parents"
This
change
was
made.

Page
16,
Para
5
"
literate"
should
be
"
literature"
This
change
was
made.

Page
21,
Para
1,
Line
6
It
appears
that
"
sits
on"
should
be
"
sites
of"
This
change
was
made.

6.2.1
Page
21
Alternate
chemical
nomenclature
is
used
in
this
section
than
elsewhere.
Suggest
changing
to
The
nomenclature
was
modified
to
be
consistent
with
the
rest
of
the
document.
13
of
18
Table
1:
Preliminary
Risk
Assessment
Header
Page
#,
Paragraph
Comments
EPA
Response
"
dodecylbenzene
sulfonate"
for
consistency.
Food
Processing
Equipment
Page
22,
first
line
Last
line
Last
word
should
be
"
estimate"
not
"
estimates"

the
sentence
should
be
changed
to
read
"..
results
in
maximum
milk
residues "
The
appropriate
changes
were
made.

Table
10
Page
30,
Footnote
a
"
hard
surfaces"
should
be
"
hard
surface"
This
change
was
made.

Table
12
Page
33
Footnote
c
The
wording
in
this
footnote
is
confusing
and
should
be
clarified
 
also,
a
")"
is
missing
adding
to
the
wording
difficulty
The
footnote
was
modified
to
improve
clarity.

Table
13
&
14
Pages
35
­
37
For
clarity,
the
DDBSA
Joint
Venture
Member
companies
do
not
support
Registration
#'
s
71094­
1
and
71094­
2
that
comprise
several
of
the
applications
for
which
the
MOE
<
100.
No
change
necessary.

Ecological
Risk
Characterization
Page
40,
Para
1
Again,
there
is
reference
to
"
vaporization"
although
the
vapor
pressure
of
DDBSA
is
very
low.
The
Agency
agrees,
and
any
references
to
vaporization
has
been
corrected
to
say,
"
not
likely
to
be
volatile."
Residential/
Occupational
Data
Gaps
Page
41
The
request
for
additional
data
for
dermal
exposure
studies
is
inconsistent
with
the
Agency's
conclusions
regarding
lack
of
need
for
dermal
assessment
(
see
page
34
for
example).
The
Task
Force
also
believes
that
more
realistic
exposure
estimates
will
show
that
the
scenarios
outlined
in
this
assessment
are
extreme
and
unrealistic
and
that
specific
information
on
DDBSA
inhalation
is
unnecessary.
This
comment
is
not
an
"
error
correction
comment"
but
an
opinion
regarding
the
need
for
monitoring.

Error
Only
Comments:
DDBSA
DRAFT
Occupational
and
Residential
Exposure
Assessment
Table
2:
Occupational
and
Residential
Exposure
Assessment
Header
Page
#,
Paragraph
Comments
EPA
Response
Executive
Summary
Page
4,
Para
1
The
Agency
concludes
that,
due
to
concentration
of
DDBSA
in
the
dust
used
in
the
inhalation
study
with
monkeys
being
only
13%,
the
conclusions
are
`
underestimates'
of
risk.
As
noted
in
the
Preliminary
Risk
Assessment
comments,
The
Agency
has
removed
the
statement
"
The
values
in
this
assessment
are
considered
to
be
underestimations
of
the
potential
risks
that
arise
14
of
18
the
study
intentionally
enhanced
absorption
of
the
dust
and
the
results
were
consistent
with
and
concluded
to
be
due
to
irritation
of
the
lungs.
In
addition,
the
Agency
has
corrected
for
the
concentration
of
DDBSA
in
the
dust
even
though
it
was
concluded
by
the
authors
that
the
primary
effects
were
the
result
of
irritation
from
the
dust
and
not
a
result
of
specific
chemical
toxicity.
Therefore,
the
assumption
of
underestimating
risk
is
in
error.
Further,
the
extensive
use
of
DDBSA
in
laundry
detergents
without
significant
hazard
to
humans
clearly
supports
the
conclusion
that
the
estimates
from
this
study
are
highly
conservative
not
"
underestimates"
of
toxicity
and
risk.
from
exposure
to
alkylbenzene
sulfonate."
However,
the
inhalation
toxicity
endpoint
only
represents
13%
active
ingredient,
and
was
not
adjusted.
In
comparison,
all
the
exposure
estimates
are
presented
on
an
active
ingredient
basis.
Thus,
the
Agency
believes
that
the
inhalation
risks
are
underestimated.

Data
Limitations 
Page
5,
1st
Bullet
AD
is
requesting
monitoring
data
for
DDBSA
 
the
Agency
should
consider
that
only
0.1%
of
the
total
DDBSA
production
is
used
in
the
registered
antimicrobial
products.
Therefore,
monitoring
data
would
be
of
no
value
since
the
potential
exposure
from
laundry
and
dish
detergents
would
confound
the
interpretation
of
any
positive
findings.
This
comment
is
not
an
"
error
correction
comment"
but
an
opinion
regarding
the
need
for
monitoring.

Table
5
Page
16,
1st
Row
Change
"
2o
oz/
gal"
to
"
2
oz/
gal"
This
revision
was
made
PHED
Page
33
It
should
be
noted
that
many
activities
associated
with
cleaning
equipment
etc.
in
food
processing
facilities/
plants
are
performed
virtually
"
hands
free"
with
solutions
pumped
from
truck
to
tank
without
exposure
to
workers.
Therefore,
the
use
of
PHED
data
is
often
inappropriate
for
these
procedures.
The
Agency
acknowledges
this
comment,
but
is
required
to
use
the
best
available
data,
which
include
CMA
and
PHED
unit
exposure
values.
This
is
not
an
error
comment,
but
an
opinion
regarding
the
methodology
of
the
assessment.
The
Agency
asks
the
registrants
to
provide
details
(
description,
quantities
handled,
etc)
about
the
different
activities,
such
as
CIP
(
Cleaning
in
Place)
so
that
the
assessment
can
be
further
refined.

Error
Only
Comments:
DDBSA
DRAFT
15
of
18
Toxicology
Disciplinary
Chapter
Table
3:
Toxicology
Disciplinary
Chapter
Header
Page
#,
Paragraph
Comments
EPA
Response
21/
28­
Day
 
Page
9,
Para
1
The
word
"
were"
should
be
"
was"
This
change
was
made.
90­
Day
Inhalation
Page
9,
Para
2
The
summary
should
include
a
statement
that
the
detergent
was
"
dried
and
micronized
to
make
it
respirable"
to
avoid
misunderstanding
of
potential
exposure
to
laundry
detergent.
This
change
was
made.

Page
9,
Para
3
Period
missing
following
3rd
sentence.

The
summary
should
include
reference
to
the
lung
lesions
in
groups
2,
8
(
LOAEL
selected
by
the
Agency),
9,
10,
11,
and
12
that
included
chronic
bronchiolitis
characterized
by
infiltration
of
mononuclear
macrophages
and
lymphocytes,
bronchiolar
fibrosis,
nonsuppurative
alveolitis,
hypertrophy
and
hyperplasia
of
the
bronchiolar
epithelium
(
including
squamous
metaplasia).
In
addition,
the
summary
should
conclude
that
the
lung
lesions
were
considered
to
be
a
response
to
irritation
from
the
dust
and/
or
related
to
the
enzyme
added.
It
is
reasonable
to
conclude
that
the
body
weight
change
in
the
10
mg/
m3
(+
enzyme)
used
by
the
Agency
to
select
the
LOAEL
was
a
result
of
the
lung
lesions
and
not
chemical
toxicity.
Based
on
all
of
the
above
information,
the
selection
of
the
NOAEL
for
this
study
should
be
considered
highly
conservative.
This
is
not
an
"
error'
comment.
However,
the
Agency
will
revise
the
text
to
mention
the
lung
lesions
in
a
future
version,
and
consider
additional
characterization
of
the
inhalation
monkey
study.

Page
11
There
are
several
places
on
this
page
where
"
mg"
is
typed
as
"
mi"
or
"
ma"
This
change
was
made.

Carcinogenicity
­
Rat
Page
15,
Para
1
"
LD"
in
the
last
line
should
be
"
LD50"
and
"
SIDDBS"
should
be
"
SDDBS"
This
change
was
made.

Error
Only
Comments:
DDBSA
DRAFT
Dietary
Exposure
(
memo
from
R.
Quick
dated
2/
8/
06)
16
of
18
Table
4:
Dietary
Exposure
Header
Page
#,
Paragraph
Comments
EPA
Response
Food
Contact
Surfaces
Page
4
The
EPA
default
value
for
product
use
is
1
mg
product/
cm2
cleaned.
The
DDBSA
Joint
Venture
believes
that
this
value
is
2­
3
orders
of
magnitude
too
high
and
data
currently
being
generated
by
industry
will
so
indicate.
The
Agency
realizes
that
the
default
value
of
1
mg
product/
cm2
may
be
too
high
and
that
its
use
may
result
in
a
calculation
of
residues
in
high
DDBSA
residues
in
food.
However,
there
are
no
actual
residue
data
available
to
use
in
estimating
residues
of
DDBSA
resulting
in
food
from
this
use.
When
data
being
generated
by
industry
are
submitted,
the
Agency
will
be
able
to
provide
a
better
estimate
of
residues
likely
to
result
in
food
from
contact
on
DDBSAtreated
food
contact
surfaces.
Fruit
and
Vegetable
Wash
Page
7
Please
note
that
the
DDBSA
Joint
Venture
does
not
support
this
use
and
does
not
have
any
Member
Company
that
has
this
use
on
their
labels.
There
are
labels
that
state
this
use
and
need
to
be
included
in
the
assessment.
Consequently,
the
Agency
must
consider
DDBSA
residues
on
fruit
and
vegetables
that
will
result
from
the
registered
use.
This
dietary
risk
assessment
is
not
intended
to
imply
that
the
Joint
Venture
is
responsible
for
responding
to
the
fruit
and
vegetable
wash
considerations.
Issues
that
must
be
resolved
Page
9,
Para
1
The
second
sentence
needs
to
be
reworded.

It
is
not
clear
what
the
"
Issue"
is
in
these
citations.
This
should
be
clarified.
This
text
was
modified
to
improve
the
clarity.
The
issues
are
as
follows:
1.
Under
40
CFR
180.940
(
b),
dodecylbenzenesulfonic
acid
solutions
containing
up
to
5.5
ppm
can
be
used
on
dairy
processing
equipment
and
food
processing
equipment
and
utensils.
Under
40
CFR
180.940
(
c),
dodecylbenzenesulfonic
acid
solutions
containing
up
to
400
ppm
can
be
used
on
food
processing
equipment
and
utensils.
The
registrant
and
user
may
have
difficulty
in
distinguishing
between
food
processing
equipment
and
dairy
processing
equipment.
Would
some
users
consider
that
food
processing
equipment
includes
dairy
processing
equipment?
Some
labels
bear
use
directions
with
a
treatment
rate
of
greater
than
5.5
ppm
for
dairy
processing
equipment.

2.
Also,
the
40
CFR
940
citations
do
not
specifically
state
that
the
solutions
may
be
used
on
food
contact
articles
including
dishes,
pots
and
pans,
glasses
etc.
However,
there
are
many
labels
registered
for
use
on
these
sites.

Error
Only
Comments:
DDBSA
DRAFT
Inert
Ingredient
Dietary
Risk
(
memo
from
L.
Keifer
dated
2/
9/
06)
17
of
18
Table
5:
Inert
Ingredient
Dietary
Risk
Header
Page
#,
Paragraph
Comments
EPA
Response
Use
of
Model
in
Inert
Risk
Assessment
Page
8
A
"
Figure
1"
is
referenced
but
no
figure
is
included
in
the
document;
Tables
should
be
aligned
so
they
can
be
read.
This
change
was
made.

Error
Only
Comments:
DDBSA
DRAFT
Ecological
Hazard
and
Environmental
Risk
Assessment
Table
6:
Ecological
Hazard
and
Environmental
Risk
Assessment
Header
Page
#,
Paragraph
Comments
EPA
Response
Confirmatory
Data
Required
Page
13
The
Agency
is
requiring
acute
toxicity
studies
with
fish
and
invertebrates
based
on
apparent
differences
in
toxicity
by
alkyl
chain
length.
The
Joint
Venture
believes
that
this
variability
in
toxicity
is
not
due
to
chain
length,
but
rather
the
techniques
used
in
the
studies
to
introduce
the
test
chemical.
DDBSA,
like
other
surfactants,
are
toxic
to
aquatic
organisms
due
to
the
mechanical
effects
of
the
surfactant
and
not
chemical
toxicity
per
se.
The
method
of
testing
often
impacts
the
bioavailability
of
these
chemicals.
Therefore,
the
Joint
Venture
believes
these
additional
tests
are
unnecessary.

A
more
detailed
response
to
these
data
requirements
will
be
provided
during
the
Public
Comment
period.
This
comment
is
not
an
"
error
correction
comment"
but
an
opinion
regarding
the
need
for
guideline
studies.

Error
Only
Comments:
DDBSA
DRAFT
Product
Chemistry
Table
7:
Product
Chemistry
Header
Page
#,
Paragraph
Comments
EPA
Comments
Chemical
Overview
Page
1
"
Benzene
Sulfonic
Acid"
is
incorrect.
Should
be
"
Dodecylbenzene
Sulfonic
Acid"
This
change
was
made.

Water
Solubility
Page
1
The
Agency
used
EPISUITE
to
determine
water
solubility.
EPISUITE
does
not
adequately
estimate
water
solubility
of
surfactant
molecules.
The
HPV
Chemical
Challenge
submission
for
LAB
indicates
values
up
to
400
grams/
liter
and
also
discusses
cloud
points
typical
of
surfactant
molecules.
Information
from
Confidential
The
document
was
modified
as
appropriate.
18
of
18
Table
7:
Product
Chemistry
Header
Page
#,
Paragraph
Comments
EPA
Comments
Statements
of
Formulations,
available
to
the
Agency,
will
indicate
that
the
solubility
of
DDBSA
in
water
is
very
high
and
the
free
acid
may
actually
be
miscible
with
water.
