						

					

	

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF PREVENTION,

 PESTICIDES AND

TOXIC SUBSTANCES

MEMORANDUM

DATE:		August 8, 2006

SUBJECT:	Alkylbenzene Sulfonates (ABS):  EPA Response to Public Comments
on EPA’s Risk Assessment. PC Codes: 079010, 190116 and
098002.(active); 790102, 790116, 790101 (inert) Case No. 4006.  DP
Barcode: D323960

FROM:	Deborah Smegal, MPH, Toxicologist/Risk Assessor

		Ayaad Assaad, PhD.  Toxicologist

		Health Effects Division (HED) (7509P)

		And

		Talia Milano, Chemist 

		Richard Petrie, Agronomist

		Cassi Walls, PhD, Chemist

		Najm Shamim, Ph.D. Chemist

		Antimicrobials Division (AD) (7510P)

THRU:		Michael S. Metzger, Branch Chief

		Whang Phang, Senior Scientist

		Reregistration Branch I

		Health Effects Division (HED), (7509P) 

TO:		Heather Garvie, Chemical Review Manager, Reregistration Team 36

		Regulatory Management Branch II

		Antimicrobials Division (7510C) 

        

The following comments are submitted by the DBSA Steering
Committee/Joint Venture.  

COMMENT 1.  Page 4 – Last Paragraph:  “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.”

Response:  DDBSA is not a skin sensitizer based on extensive human
exposures from laundry and dish detergents.  Further, the SIDS Dossier
for LAS provides three negative guinea pig studies, listed in the IUCLID
dossier (pages 268-269), and a report of 2 human HRIPT tests that were
negative, listed on pages 305-306.  Note also that the conclusion on
page 25, “LAS does not have significant skin sensitization
properties” was accepted in this review process.  The overwhelming
evidence from the available animal and human studies is that LAS (and
DDBSA) are not skin sensitizers.  The conclusion reached in the RED
review, therefore, should be changed.  For additional details, please
see our reply to the Response to Errors Only comments below and comments
provide by CLER.  

EPA Response:  The risk assessment and toxicity memo were revised to
state that the alkylbenzene sulfonates are not dermal sensitizers.  

COMMENT 2.  Page 12 – Physical and Chemical Properties

The following paragraph appears on Page 8:  

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.

The JV would like to raise two points regarding this information. 
First, it is not clear to the JV why the distinction is made between
“food processing equipment” and “dairy processing equipment” in
the regulation since dairy equipment is, in fact, food processing
equipment.  Second, a concentration of 5.5 ppm is not considered to be
an adequate sanitizer concentration as the length of time for adequate
sanitization would be extensive, if even feasible.  Proper sanitization
of dairy equipment and other food processing equipment requires
approximately 200 to 400 ppm of DDBSA.  The JV agrees with the Agency
that the risk assessments should be performed on the higher
concentrations.

EPA Response:  No change to the risk assessment is necessary.  The
Agency intends to propose revisions to 40 CFR that reflect the higher
rate on diary processing equipment currently listed on the product
labels.  

COMMENT 3.  Page 12 – Physical and Chemical Properties

Response:  Please see our reply to the Agency’s Response to Errors
Only Comments below regarding the molecular weight and molecular
formulae in Table 1.  Also, we have been informed by the LAS Producers
that the chemical structures as shown are incorrect – please see
comments from the LAS Producers group, CLER.

EPA Response:  The risk assessment was modified as recommended.  The
chemical structure was replaced as suggested.  

COMMENT 4.  Table 13 (Page 36-38) – Short and Intermediate-Term
Inhalation Risks for Occupational Handlers

Response:  The use of high volume (e.g. 10,000 gallons/day) exposure to
cleaning solutions is inappropriate because these procedures are
performed with minimal human exposure.  For Cleaning in Place (CIP)
procedures, the following has been prepared to explain the procedures
and potential worker exposures.  As clearly shown, worker exposure to
more than a minimal volume of cleaning solution does not occur. 
Further, when workers use concentrated solutions (prior to dilution),
PPE is always required.  The JV believes the other scenarios in Table 13
for which high volume exposure is assumed also use procedures that
provide for only minimal worker exposure.

Discussion of Exposure Potential to Workers during Cleaning in Place
(CIP) Operations-

Prepared by  F.A. Heitfeld (JohnsonDiversey)

Overview of CIP

Cleaning in Place (CIP) operations are common in large industrial
manufacturing facilities.  While associated with the food, beverage,
brewing, and dairy industries, CIP operations occur in a wide variety of
industrial applications including pharmaceuticals and in industrial
chemical production.  CIP applications often utilize multiple cleaners,
not all of which are EPA regulated pesticides.

CIP systems automate the cleaning and sanitization process for
industrial process equipment, such as product lines, tanks, vessels,
etc.  Some of the advantages of these systems are: 

CIP allows easy cleaning of process equipment that is not easily
accessible to its operators.

CIP eliminates the need to disassemble equipment for cleaning.  

CIP prevents worker and environmental exposure to harmful production or
cleaning chemicals. 

Automatic cleaning prevents contamination of the production process. 

CIP systems provide more consistent and reproducible cleaning. 

The cleaning process is automated possibly reducing staffing
requirements for the process line. 

Production down time can be reduced. 

Minimize the amount of cleaners and water used to clean.

CIP systems consist of the following major elements.

1.  PLC (Programmable Logic Controllers)- this is a programmable unit
that initiates and controls the CIP operations in a production facility.
 

2.  Chemical storage- This is the area where concentrated cleaners and
biocides are stored.  Typical storage containers range from Drums (30-55
gallon) and totes (220-330 gallon) up to storage tanks that are filled
from tank trucks or rail cars.  Some systems pump an aliquot of
concentrate into a separate tank (day tank) before use.  This prevents
contamination of the concentrate if the system malfunctions.  There is
no additional exposure since the transfer process is closed and pumping
is automatically controlled by the system.   

Chemical Pump –Chemical pumps are normally PLC controlled via time or
conductivity.  The pump controls total flow through the CIP loops and
plays an important role in chemical dilution.  Time based dosing systems
add chemical based on the chemical pump’s capacity to pump x volume in
y amount of time.  Conductivity based systems add chemicals via a
conductivity probe which controls the chemical pump via a PLC.

Recirculation – CIP systems start with a cold water rinse.  The rinse
is designed to first verify all connections have been correctly made. 
Second it removes loose and soluble soils.  There can be up to 3
individual rinse steps.  Rinses are bursts of limited amounts of water
to remove loose and soluble soils.  Next, water is added to the system
and re-circulation is established.  Once re-circulation is established,
the cleaner is added to the system.  When completed, heat is applied to
the solution, via a heat exchanger, to establish the correct cleaning
temperature – all controlled by the PLC.  The PLC recirculates the
solution for the predetermined amount of time.  The cleaning solution is
drained.  1-3 cold water burst rinses to remove cleaning solution.  The
sanitizer is circulated after all cleaning steps are completed.  

Cleaning Circuits- Most CIP systems consist of a number of individual
circuits which typically correspond to a discrete section of the
production line (e.g. one tank and its associated piping or a single
transfer pipeline).  All circuits use a known volume of water. 

The design of CIP systems are customized for each individual facility
based on the needs and requirements of the process.  The number of
circuits depends on the size of the production facility, how many
processing lines, tanks, fillers, etc being cleaned and the time
available each day for cleaning.  Large facilities, that cannot tolerate
being out of production for very long, may have two or more independent
CIP systems in use at one time.  Each CIP system would typically clean
one circuit at a time.

Circuits are often divided into two types:

1.  Line circuits- CIP circuits designed to clean the piping used in the
production process.  These circuits tend to use the most water.  This
can be between 100 and 1000 gallons depending on the length of piping
and its diameter.  Most common circuits are between 100 and 300 gallons.

2.  Tank circuits- CIP circuits designed to clean a tank and the process
piping to the tank.  Usually, these have a 1 tank per circuit limit. 
Tank circuits typically require only 40-100 gallons to clean.  The
variable here is the size of the tank and the volume of its associated
piping.  The amount of CIP solution needed for the circuit must be
sufficient to fill the circuit piping and the bottom of the tank (to
maintain the prime for the pump) as well as to cover the walls of the
tank.  The tank itself is never filled completely with CIP cleaners.  It
is possible for a 20,000 gallon tank to be cleaned with only 50 gallons
of solution.

Tanks are cleaned by spraying the cleaning solution through “spray
balls” which are high technology sprinklers designed to spray all
interior surfaces of the tank.  Spray balls have various spray patterns
depending on the type of tank, i.e. horizontal versus vertical, tanks
with mixers, fixed blades, etc.  This operation is essentially enclosed;
however, some systems require that the tank be vented to prevent
implosion if the temperature of the cleaning liquid changes from hot to
cold.    

The overall design of CIP systems can be broken down in to two main
types:

1.  Once through Systems called Single Use Systems- The cleaning
solution is sent through the system and then directly drains into the
facility waste water management system.

2.  Recirculation systems called Re-Use Systems- the cleaning solution
is re-used many times to clean multiple circuits before draining into
the facility waste water management system.  Re-Use systems typically
require less product than single use systems.

CIP Cleaning Cycles and the use of Biocides:

Biocide use is only a small part of the CIP process.  The standard
progression of cycles consists of the following:

1.  Rinse with water to remove soil from the process equipment.

2.  Detergent treatment to remove remaining soils (may be heated)

3.  Water rinse to remove detergent chemicals (may be heated).

4.  Acid wash or Acid rinse for hard water areas or high calcium foods
(may be heated)

5.  Water rinse to remove acid detergent

6.  Sanitizing with no rinse (usually at ambient temperatures)

Note: If using an acid sanitizer steps 4 and 5 may be eliminated or used
less frequently depending on scale formation.

Each plant/facility has its own customized program for cleaning and
sanitizing based on its unique requirements.  The actual duration of the
sanitizing cycle is short (1-2 minutes typical, 5 minutes maximum).

Worker Exposure to Chemicals during CIP Operations

CIP systems are designed to limit worker exposure to cleaning chemicals
while still insuring a high level of hygiene to critical industrial
processes.  The majority of CIP operations are automated and do not
require workers to come into contact with the cleaning chemicals.  There
is, however, some potential for worker contact in the following areas:

1.  Connection of Totes and Drums to the CIP system:   Many CIP systems
use concentrated cleaning products in totes or drums.  These have to be
manually installed into the system.  This operation is analogous to the
pump liquid use pattern.  Once the tote or drum is in place, the worker
opens the container and installs a pickup tube or probe that conveys the
concentrated product into the CIP system for dilution.  Totes either use
the probe or pick up tube or a connection to the tote outlet valve. 
Once installed, the worker can leave the area.  Conversely, when the
drum or tote is empty, the probe or tube is withdrawn and transferred to
a fresh container.  Please note, that since many of these products are
corrosive, significant PPE (e.g. goggles, gloves) is required under OSHA
regulations.  

In most plants, the use-period for a drum or tote ranges from 1 week to
1 month.  Thus, changeover operations occur on a regular, but infrequent
basis.  

Possible areas of worker exposure include:

a.  Dermal exposure to drainage of concentrated product from the pick-up
tube as it is removed from the tote or drum.

b.  Dermal exposure to residual concentrated product on the outside of
the pick-up tube during transfer from the empty to the full tote or
drum.

c.  Inhalation exposure to vapors from volatile materials released
either from the open totes/drums or from the residual product associated
with the pickup tube. 

The exposure scenarios described above are NOT volume dependent.  Once
installation is completed, the worker can leave the area and conduct
other duties.  The actual amount of time involved in removing a spent
container and installing a new container is typically 5-10 minutes on a
weekly to monthly basis.  Thus, the actual volume of product pumped
through the system is irrelevant to the amount of worker exposure in
this case.

2.  Delivery of bulk concentrates to storage tanks within the facility: 
Larger processing facilities may take delivery of cleaning chemicals in
bulk from either trucks or tank cars.  In these cases, the material is
pumped from the delivery vehicle into a storage tank in the facility.  

Possible areas of worker exposure include:

a.  Dermal exposure to drainage of concentrated product from the hoses
used to transfer product from the delivery vehicle to the facility
storage tank.  If dry-break couplings are used, exposure should be
minimal.  

b.  Inhalation exposure to vapors from volatile materials released if
product spills during transfer operations.  

The exposure scenarios described above are also NOT volume dependent. 
Exposure will likely occur once the product transfer is completed and
the hose is disconnected for storage.  If dry-break couplings are not
used, some product spillage may occur resulting in potential worker
exposure to the concentrate.  The amount of spillage (if any) will be
dependent on the size of the hose, but not on the amount of material
transferred to the facility.  Again, significant PPE is required under
OSHA regulations since many of these materials are corrosive.

3. Exposure to use-dilution product and vapors during CIP system
changeovers.  CIP systems require a positive disconnect from the
production line in food and beverage plants to prevent accidental
contamination of production product with CIP cleaning and sanitizing
solutions.  At the end of a CIP cycle, the system is shut-off, and a
worker must physically disconnect the piping connecting the CIP system
to the production line in order to prevent contamination of product with
CIP chemicals.  Potential exposure to the sanitizing solution may occur
if there is drainage of use-solution from the piping during this
operation.  It typically takes only 1-2 minutes to move a plumbing or
hose connection but may have to be repeated 5-10 times if multiple
circuits are involved.  Since CIP cleaning typically occurs once per
day, only one shift would be involved in this operation.

4.  Exposure to use-dilution vapors/mists during tank cleaning:  In some
systems, tank cleaning has the potential for limited worker exposure to
vapors or mists from use-dilutions of some cleaning products.  CIP
cleaning solutions (not biocides) are often prepared at elevated
temperatures.  To prevent tank implosions when a cold solution is
sprayed into a hot tank, some of the access ports are left open to allow
the air pressure inside the tank to equalize with the pressure outside
of the tank.  Large tanks are more vulnerable than smaller tanks.  

A worker in the immediate vent area may be exposed to mists or splashing
from these vents from the diluted cleaning product.  Since CIP systems
are automated, workers are typically not in the area during tank
cleaning.  If a worker was present, exposure to the biocide solution is
expected to be brief- at most, exposure would only occur for the 1-2
minutes duration of a biocide CIP cycle.  Recently implemented best
practice includes the installation of a temporary tank door to minimize
escape of the CIP solution while allowing for adequate venting to
prevent tank collapse.  All facilities require respiratory protective
equipment if tank entry is necessary, as these are classified by OSHA as
confined spaces.  

Recommendations:

1.  Worker exposure during CIP operations is limited.  One of the
advantages of these systems is to reduce worker contact with cleaning
chemicals by automating the dilution and cleaning processes.  The
Agency’s assumption that workers are exposed to the equivalent to the
exposure from manual pouring 10,000 gallons per day is unreasonable.  

2.  Routine but occasional worker exposure to cleaning chemicals in CIP
systems should be presumed to occur during connection and/or
disconnection of the cleaning concentrate container to the CIP system. 
Exposure to the use-dilution may occur when the CIP system is manually
disconnected from the production line.  

a.  Worker exposure from both of these operations is NOT expected to be
volume dependent for routine CIP operations.

b.  Concentrate reservoirs (totes or drums) are replaced approximately
once a week to once a month in most systems.  This operation only takes
5-10 minutes.  Since most CIP biocidal concentrates are corrosive, PPE
is required under OSHA regulations.  Workers do not remain in the area
after the connections are made and the “pumping” occurs over a
period of days or weeks, and only when the CIP system is in operation.  

c.  During the positive disconnect of the CIP system, some worker
exposure to the use-dilution of the biocide product.  While the CIP
system is turned off during the change-over, some drainage may occur. 
Workers would be exposed to the product during the 1-2 minutes required
to move the pipe or hose connection.  This operation may have to be
repeated 5-10 times if multiple circuits are involved.  The frequency of
this operation is approximately once per day (< once per shift).  

EPA Response:  The Agency modified the assessment and calculations so
that more appropriate unit exposure values were used for the assessment
of CIP systems.  The unit exposure value selected takes into account the
low potential for worker exposure as addressed by this comment. 
However, the amount handled/treated parameter of 10,000 gallons/day was
still used because this numerical value represents size of the system
being treated.  

COMMENT 5.  Table 13 (Page 37) – Shower Stalls and Toilets

Response:  According to the Agency’s Response to Errors Only Comments,
the Shower Stalls and Toilets scenario is developed from Product
Registration 3635-279.  A review of this label indicates that the
product is 15.52% DDBSA as stated by the Agency.  However, there are no
“Wiping” procedures on the label that use concentrated product
(1.49# a.i./gallon) and 1 liter (0.26 gallons/day).  That is, all wiping
procedures occur after dilution of the product to 1-2 oz/gal.

EPA Response:  The Agency agrees with this comment and has modified the
Occupational and Residential Exposure Chapter as well as the risk
assessment to reflect this dilution.

COMMENT 6.  Section 11.0 Deficiencies/Data Needs – Ecological Data
Gaps and 

Label Hazard Statements for Terrestrial and Aquatic Organisms

The Agency indicates that Acute Freshwater Fish and Acute Freshwater
Invertebrate studies are required.  The Agency indicates that an
environmental hazard statement for manufacturing use products is
required for fish and aquatic invertebrates.  

Response:  This requirement is based on a lack of information for
toxicity of C12-C16 BSA to fish and an EC50 of < 1.0 ppm for C14/16 for
invertebrates.  According to CLER, benzene sulfonic acid, C10-C16 alkyl
derivatives (CAS RN 68584-22-5) contain less than 1% of the C15 or C16
homologues, the C14 component is a minor fraction of the composition (<
15%) and the average alkyl chain lengths for LAB sulfonic acids have the
same range (C11.3-C12.6) as LAS and likely have the same overall
weighted average chain length as LAS, C11.7. 

Data from the LAS SIAR and/or the HPV submission for LAB, report at
least 16 fish studies and 17 freshwater aquatic invertebrate studies on
commercially relevant LAS and LAB (average alkyl chain length
approximately 11.7) that followed standardized (EPA and OECD guideline)
test methods.  The fish LC50 values ranged from 1.67 to 7.7 mg/L for LAS
and from 3 to 10 mg/L for the LAB sulfonic acids.  The invertebrate EC50
values range from 1.62 to 9.3 mg/L for LAS and from 2.9 to 12 mg/L for
LAB, including the C10-C16 benzene sulfonic acid and dodecylbenzene
sulfonic acid.

These data demonstrate that no environmental hazard statement is
required for DDBSA per se, because the EC50 values for fish and aquatic
invertebrates are all greater than 1 mg/L.  Further, these data indicate
that additional testing of DDBSA in aquatic species is unnecessary.  It
should be noted that the majority of the current labels from JV-Member
Companies include the statement, “This product is toxic to fish”
based on the mixture of DDBSA with phosphoric acid.

EPA Response:  The Agency has revised the ecological data gaps and label
hazard statement.  

COMMENT 7.  Section 11.0 Deficiencies/Data Needs –
Residential/Occupational Data Gaps

The Agency indicates a need for worker exposure studies that evaluate
inhalation exposure for indoor uses.

Response:  The industry has several task forces generating data
pertinent to this request that should provide improved values for these
assessments.

EPA Response:  No change necessary.  Once the task forces submit these
data, and they are reviewed by the Agency, the values will be considered
for refining the assessment.

COMMENTS: ALKYLBENZENE SULFONATES (ABS) TOXICOLOGY CHAPTER 

FOR THE REREGISTRATION ELIGIBILITY DECISION (RED) DOCUMENT.  PC CODE:
079010, 190116 AND 098002.  CASE NO.  4006. DP BARCODE: D327886

The Agency has changed the section on Page 10 related to the inhalation
studies in monkeys to read as follows:  “In this published study, the
detergent was dried and micronized to make it respirable.  However, it
should be noticed that most uses of this detergent are in liquid form. 
It is a common misconception that the small particle size used in an
animal study (MMAD of 1-3 um in acute studies, 1-4 um in multiple
exposure studies) has no relevance to the large particle size that comes
from medium to coarse powdered material or a liquid-powder mix during
use.  Detergents are typically mixed with large quantities of water
before use.  When the aqueous mix is used, droplets rapidly shrink as
they fall due to water evaporation.  The degree of shrinkage depends on
temperature, relative humidity, particle size, and the length of time
that the droplets are suspended in the air.  Since humans are capable of
inhaling particles >100 um, it is reasonable to expect a significant
portion of these particles to be inhaled.  While most large particles
are captured in the nose, some are capable of reaching the lungs.  Large
particles have the potential to do considerable local damage if they are
respirable because of the volume of material they contain.”

Response:  Please see detailed comment in our reply to the Agency’s
Response to Errors Only Comments below and in the previous comments
provide by S. Little to H. Garvey on May 30, 2006.

In addition, the summary of the study 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).  Further, 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.

EPA Response:  The Agency revised the summary of the inhalation monkey
study.  

COMMENTS: OCCUPATIONAL AND RESIDENTIAL EXPOSURE ASSESSMENT OF
ALKYLBENZENE SULFONATES (ABS) FOR THE REREGISTRATION ELIGIBILITY
DECISION DOCUMENT (RED).  CASE NO.  4006. DP BARCODE: D327732

Page 6 – Data Limitations and Uncertainties – First Bullet:  “Most
of the CMA data are of poor quality; therefore, AD requests that
confirmatory monitoring data be generated to support the values used in
these assessments.”  

Response:  The industry has several task forces generating data
pertinent to this request that should provide improved values for these
assessments.  Further, DDBSA-specific monitoring would be extremely
difficult because of the extensive use of DDBSA in laundry and dish
detergents.

EPA Response:  No change necessary.  

COMMENTS: PRODUCT CHEMISTRY SCIENCE CHAPTER FOR DODECYLBENZENE SULFONIC
ACID, C10-C16 DERIVATIVES AND SODIUM SALT.  CASE NO.  4006. DP BARCODE:
D327731

The Agency changed the water solubility from the original draft version
for C10-C12 DDBSA (CAS RN 68584-22-5) to 400 grams/liter but did not
similarly change the water solubility of C12 DDBSA (CAS RN 27176-87-0),
retaining the value of 0.7 mg/L.

EPA Response:  The document has been revised.  

COMMENTS: RESPONSE TO ERROR COMMENTS ON THE ALKYLBENZENE SULFONATES
(ABS) PRELIMINARY RISK ASSESSMENT.  PC CODE: 079010, 190116 AND 098002. 
CASE NO.  4006. DP BARCODE: D323960

1.  Following is the argument offered by EPA’s reviewing toxicologist
in response to our Errors Only Comment that it is inappropriate to
conclude that DDBSA is a mild to moderate skin sensitizer:

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).  In addition, there was evidence of sensitization in the monkey
inhalation study, which supports the Agency’s classification.

The data cited in the above paragraph for guinea pig studies are
actually included on page 486 in the following citation and the stated
Toxicologist citation does not appear to cite the specific data
(although the Robinson et al. reference below cross references the
Toxicologist abstract):

Robinson, M.K., Stotts, J., Danneman, P.J., Nusair, J.L. and Bay, P.H.S.
(1989).  A risk assessment process for allergic contact sensitization. 
Fd. Chem. Toxic.  27:479-489.

In reaching the conclusion that DDBSA is a weak sensitizer from this
information, however, EPA’s reviewing toxicologist has overlooked the
paragraph that follows the information from the guinea pig studies. 
This paragraph is reproduced below:

Human sensitization testing was conducted with LAS alone (on 2294
subjects) and LAS in various product formulations (on 17,887 subjects)
at LAS concentrations ranging from 0.001 to 0.113% (Fig. 4).  The HRIP
tests of LAS solutions covered 17 commercial batches of LAS, and over
100 commercial batches of LAS were used in the products tested in the
HRIPTs.  None of the test subjects (more than 20,000) showed evidence of
a skin sensitization reaction (Nusair et al., 1988).  As a result,
provocative use testing was unnecessary.  Extended product use testing
showed no evidence of sensitization or any other skin reactions (Fig.
4).  Of 79 consumers with skin problems alleged to be associated with
the use of LAS-containing products, and who were patch tested with
solutions of the LAS-containing products, none gave a positive patch
test result. 

While the concentrations tested in the human studies are lower than
those in the guinea pig studies, the concentrations in the human tests
are representative of the potential exposure concentrations in the
scenarios used in EPA’s risk assessments.  Most importantly, it is
standard practice within EPA to utilize human patch test data in
reaching conclusions on skin sensitization potential when there is
disparity between the human and animal data.  Further, the sheer volume
of human tests must be considered highly significant in showing that
these types of surfactants are not skin sensitizers.  Based on
information previously provided (Memo from J. Van Miller to H. Garvey of
April 11, 2006), the cited ‘sensitization in the monkey inhalation
study’ is readily ascribed to the known effects of the enzymes in the
dust used in the study.  As stated in the comment on the Preliminary
Risk Assessment above, the overwhelming evidence from the available
animal and human studies is that LAS (and DDBSA) are not skin
sensitizers.  The conclusion reached in the RED review, therefore,
should be changed.

2.  The following response was made to our Errors Only Comment regarding
the fact that the NOAEC from the inhalation study with monkeys (MRID
43498403) should be considered a conservative estimate:

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.  

Response:  The reviewer’s comments regarding “common
misconception” of inhalable particle size and the statement that
humans can inhale particles >100 µm are confusing.  It is a well
established toxicological principle that particles of greater than 10
µm are not inhaled at any significant concentration in the lungs of
humans (see for example Figure 5 in the paper by Raabe – previously
provided).  Indeed, EPA’s own documents on determination of RfD, rely
on this principle (see for example Figure 3.3, page 3-10 – previously
provided).  This figure shows that with mouth breathing, pulmonary
deposition fraction drops to 0 (zero) with aerosols having an
aerodynamic diameter of approximately 10 µm.  Also, Figure 3.3
demonstrates that aerosols >20 µm can not reach the tracheobronchial or
pulmonary regions because they deposit in the mouth or larynx before
reaching the lungs.  Aerosols >100 µm have a sedimentation velocity
(>25 cm/sec) too great to stay airborne long enough to be available for
inhalation by humans.  Although our original comment was simply made to
ensure it was clear that the dust in the monkey study was produced to
enhance the total inhaled dose (thus making the exposure highly
conservative), and EPA has subsequently removed its reference to the
estimates being “underestimates of risk”, it is very important that
the Agency carefully reviews its procedures for risk assessment when
using non-standard and/or reinterpreted basic and long-accepted
toxicologic principles.  Further, it is not clear why the reviewer
refers to “rat” nasal turbinates when the study was conducted in
monkeys.  And lastly, if there is a foundation for the discussion of
liquid detergent drop sizes shrinking, it should be clearly provided if
it impacts the risk assessment.  In reality, exposure to aerosols of
DDBSA would not be a significant concern, the surfactancy of the DDBSA
would limit volatility, and drop size of any potential aerosol would be
large and would not be suspended for extended periods of time.   This
is supported by the data on particle sizes from aerosol spray products
included in the LAS SIAR (pp. 19-20).  The study data reported could be
considered a worst case for generation of respirable particles and yet
the results indicate the fraction under 10 microns is less than 0.1% of
the total volume sprayed and the maximum concentration in air is only
0.13 to 0.72 mg/m3.

EPA Response:  The Agency has revised the risk assessment and toxicity
chapter to state that the alkylbenzene sulfonates are not dermal
sensitizers.  In addition, the discussion of the inhalation monkey study
was revised.  

3.  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.

Response:  The chemical formula for the C16 moiety of DDBSA is C22H38O3S
with MW=382.6 [Note that the formula in the Agency’s comment excludes
the benzene ring].  However, based on recent information received from
the LAS Producers, the mean chain length distribution for DDBSA is
approximately 11.7 and therefore, the Agency may wish to use the C12
moiety as the most representative:  C18H30O3S of MW = 326.5.

EPA Response:  The document was revised.

Comments from the Council for LAB/LAS Environmental Research (CLER) and
the European Centre on Studies on LAB/LAS (ECOSOL).  

EPA Response:  The structures were replaced in the risk assessment.  

 EPA Response:  The document was revised as appropriate.    

EPA Response:  The document was modified to state that the alkylbenzene
sulfonates are not dermal sensitizers.  

EPA Response:  No change was made.  The Agency consulted a group of
senior toxicologists on the Health Effects Division (HED) Toxicity
Advisory Clinic (TAC) in selecting a NOAEL of 50 mg/kg/day for use in
risk assessment based on a weight of evidence evaluation from several
studies.  

EPA Response:  At this time, the product concentration value based on
the Procter & Gamble 2001 citation can not be used by the Agency since
the study is unpublished.  The Agency can not conduct an assessment
based on data from unpublished resources.  It would be necessary for the
Procter & Gamble data to be submitted and reviewed by the Agency before
they are utilized.  Therefore, the inhalation exposure assessment of the
pet products remains unchanged. 

EPA Response:  Deterministic exposure assessments, as conducted for LAS,
are not a function of probability.  This assessment evaluates carpet
cleaner users only therefore the argument that ingestion resulting from
the daily use of utensils/dishware washed in hand dishwashing detergents
is more likely to occur than ingestion from hard surface/carpet cleaners
is not applicable to this assessment.  Furthermore, since exposure is a
function of the method of application and use sites (i.e., dishware
versus hard/carpeted surface), different methodologies must be used
utilized for different exposure scenarios.  The statement that the
Agency’s MOEs are 1000-fold too conservative must be justified with
actual calculations for the appropriate exposure scenario.  The dishware
and carpet cleaner scenarios can not be considered equivalent especially
considering that the residue that is anticipated to remain on
utensils/dishware is expected to be significantly less than what will be
found on hard surfaces/carpets due to the fact that the
utensils/dishware are rinsed with water prior to use whereas floors and
carpets are not. 

It should be noted that AD has reassessed the hard surface/carpet
cleaner scenarios using the standard methodology that is used for
assessing active ingredients in cleaning products.  The PiRAT model does
not have specific parameters for the hard surface/carpet cleaner
scenarios and was initially used to establish a conservative estimate of
exposure when LAS is used as an inert.

EPA Response:  The Agency disagrees with this comment.  As previously
stated, deterministic exposure assessments are a function of the method
of application and use site and are not based on the probability of
occurrence.  Also, the residues that are anticipated to remain on
utensils/dishware are significantly less than what is expected to be
found on hard surfaces/carpets that are cleaned with LAS products
because once the utensils are cleaned with dishwashing detergents, they
are rinsed with water prior to use, whereas floors and carpets are not.

EPA Response:  No change was made.  The dietary risks are below the
Agency’s level of concern.  

EPA Response:  The Agency agrees that the vapor pressure of LAS is low. 
However the CMA data utilized in this assessment is based on exposure to
the aerosol particles, not the gas.  Therefore the inhalation assessment
for occupational handlers remains unchanged.

EPA Response:  The risk assessment and ecological chapter were revised
to remove the hazard statement for fish and aquatic invertebrates.  

EPA Response:  The risk assessment and ecological chapter were revised
to remove the hazard statement for fish and aquatic invertebrates.  

  Modified from http://www.dpandp-sale.demon.co.uk/cleaning.html

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