  SEQ CHAPTER \h \r 1 							

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF           

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

TXR No.  0054267

Date: July 6, 2006

MEMORANDUM

SUBJECT:	Alkylbenzene Sulfonates (ABS) Toxicology Chapter for the
Reregistration Eligibility Decision (RED) Document.  PC Code: 079010,
190116 and 098002.  Case No. 4006.  DP Barcode: D330328.

FROM:	Ayaad Assaad, D.V.M., PhD.  Toxicologist

		And

		William Dykstra, PhD., Toxicologist

		Health Effects Division (HED) (7509C)

THRU:	Alberto Protzel, Ph.D.

		Senior Branch Scientist, Tox Branch

		Health Effects Division (HED) (7509 C) 

TO:		Deborah Smegal, MPH, Toxicologist/Risk Assessor

		Health Effects Division (HED) (7509 C)

		

         

Attached is the Toxicology Disciplinary Chapter for the Alkylbenzene
Sulfonates (ABS) for the purpose of issuing a Reregistration Eligibility
Decision (RED) Document. 

  SEQ CHAPTER \h \r 1 

SODIUM DODECYLBENZENE SULFONATE

DODECYL BENZENESULFONIC ACID

BENZENE SULFONIC ACIDS, C10-16 ALKYL DERIVS.

PC Code:  079010, 098002, 190116

Toxicology Disciplinary Chapter for the 

Re-registration Eligibility Decision (RED)Document

Prepared by: 

Ayaad Assaad, D.V.M., Ph.D.

Toxicology Branch/HED

and

William Dykstra, Ph.D.

RAB 1 Branch/HED

And

Louis Scarano, Ph.D.

Toxicology Branch/HED





TABLE OF CONTENTS

 TOC \f 1.0	HAZARD CHARACTERIZATION	  PAGEREF _Toc141690936 \h  6 

2.0	REQUIREMENTS	  PAGEREF _Toc141690937 \h  7 

3.0	DATA GAP(S)	  PAGEREF _Toc141690938 \h  8 

4.0	HAZARD ASSESSMENT	  PAGEREF _Toc141690939 \h  8 

4.1	Acute Toxicity	  PAGEREF _Toc141690940 \h  8 

4.2	Subchronic Toxicity	  PAGEREF _Toc141690941 \h  8 

4.3	Prenatal Developmental Toxicity	  PAGEREF _Toc141690942 \h  11 

4.4	Reproductive Toxicity	  PAGEREF _Toc141690943 \h  14 

4.5	Chronic Toxicity	  PAGEREF _Toc141690944 \h  15 

4.6	Carcinogenicity	  PAGEREF _Toc141690945 \h  16 

4.7	Mutagenicity	  PAGEREF _Toc141690946 \h  17 

4.8	Neurotoxicity	  PAGEREF _Toc141690947 \h  18 

4.9	Metabolism	  PAGEREF _Toc141690948 \h  18 

5.0	TOXICITY ENDPOINT SELECTION	  PAGEREF _Toc141690949 \h  20 

5.2	Dermal Absorption	  PAGEREF _Toc141690950 \h  20 

6.0	FQPA CONSIDERATIONS	  PAGEREF _Toc141690951 \h  20 

6.1	Special Sensitivity to Infants and Children	  PAGEREF _Toc141690952
\h  21 

6.2	Recommendation for a Developmental Neurotoxicity Study	  PAGEREF
_Toc141690953 \h  21 

5.3	Classification of Carcinogenic Potential	  PAGEREF _Toc141690954 \h 
21 

8.0	REFERENCES	  PAGEREF _Toc141690955 \h  22 

9.0APPENDICES	  PAGEREF _Toc141690956 \h  24 

9.1	Toxicity Profile Summary Tables	  PAGEREF _Toc141690957 \h  25 

9.1.1	Acute Toxicity Table	  PAGEREF _Toc141690958 \h  25 

9.1.2	Subchronic, Chronic and Other Toxicity Tables	  PAGEREF
_Toc141690959 \h  39 

 



HAZARD CHARACTERIZATION

Linear alkylbenzene Sulfonate (LAS) is an anionic surfactant which was
introduced in 1964 as a more biodegradable replacement for highly
branched alkylbenzene Sulfonates (ABS). LAS is a mixture of closely
related isomers and homologues, each containing an aromatic ring
Sulfonated at the para position and attached to a linear alkyl chain. 
Their primary use is as a detergent for cleaning (residential,
commercial, and on surfaces where food contact occurs).

The presence of LAS in many commonly used household detergents gives
rise to a variety of

possible consumer contact scenarios such as: direct and indirect skin
contact, inhalation, and

oral ingestion derived either from residues deposited on dishes, from
accidental product

ingestion, or indirectly from drinking water.

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

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

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

Acute dietary endpoint – there were no effects attributable to a
single dose of LAS exposure and so no acute dietary endpoint was chosen.

Chronic dietary endpoint and short-term incidental oral endpoint – a
NOAEL of 50 mg/kg/day was chosen based on three different studies (see
below).  There were no susceptibility concerns for infants/children and
so the special FQPA factor of 10x may be removed and the traditional
uncertainty factors of 10 (intraspecies) and 10 (interspecies) were used
to derive a chronic RfD of 0.5 mg/kg/day.

Short-, intermediate-, and long-term inhalation exposure scenarios – a
NOAEL of 1 mg/m3 from a six month inhalation study in monkeys.  The
level of concern is 100 for both occupational and residential exposure
scenarios.

Dermal exposure scenarios – quantification of dermal risk is not
required for several reasons described below in Section 5.2, but mainly
because LAS are dermal irritants at concentrations greater than about
20% and thus dermal exposure would be self-limiting.

Following is a brief summary of the hazard assessment for LAS:

Absorption, Distribution, Metabolism, Excretion

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

 

Acute Toxicity (Including Irritation, Sensitization)

LAS exhibit a wide range of acute toxicity via the oral route in rats
(LD50s of 404 – 1980 mg/kg), with a narrower range in mice (LD50s of
1259-2300 mg/kg).  This spans the acute oral toxicity categories of
III-IV.  LAS are classified as acute toxicity category II for the dermal
and inhalation routes of exposure.

LAS is an irritant to the eye (category I), and skin (category II), but
is not a skin sensitizer.

Repeated Dose Toxicity (Subchronic and Chronic)

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

For the purposes of this hazard assessment, several studies were
considered collectively to determine a NOAEL of 50 mg/kg/day for the
chronic dietary endpoint.  The NOAELs in the three studies used to
develop the chronic endpoint are 40, 50 and 85 mg/kg/day.  The chronic
endpoint is based on:  increased caecum weight and slight kidney damage
(at a LOAEL of 114 mg/kg/d in the six month rat study); reduced body
weight in 21-day old pups (at a LOAEL of 250 mg/kg/day in a reproductive
toxicity rat study); and significant decreases in renal biochemical
parameters (at a LOAEL of 145 mg/kg/day in a nine month drinking water
study in rats).

Developmental Toxicity

A number of developmental studies via the oral and dermal routes have
been performed with LAS in rats, mice and rabbits; there were also
several subcutaneous injection developmental studies reported in mice
(WHO, 1996).  There is a spectrum of quality in the 20+ studies in terms
of dosing (some had only one or two doses), purity of LAS used (some
used formulated products that ranged from 1-45% LAS content), and overt
toxicity to the pregnant females in the dermal studies due to severe
irritating effects.  It is concluded that some developmental effects
(including some terata) were observed at high doses at which maternal
toxicity was observed and the available information does not suggest any
qualitative or quantitative susceptibility differences between pups and
pregnant animals.

Reproductive Toxicity

LAS were tested in several multigeneration studies in rats.  There were
no effects on reproductive parameters in any of these tests at doses up
to 250 mg/kg/day.

Carcinogenicity

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

Genotoxicity

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

Neurotoxicity

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

  TC \l1 "1.0	HAZARD CHARACTERIZATION 

2.0	REQUIREMENTS  TC \l1 "2.0	REQUIREMENTS  

The requirements for an indirect food use for Linear alkylbenzene
Sulfonate (LAS) are in Table 1. 

Table 1.

Test 

	Technical

	Required	Satisfied

870.1100	Acute Oral Toxicity

870.1200	Acute Dermal Toxicity

870.1300	Acute Inhalation Toxicity

870.2400	Primary Eye Irritation

870.2500	Primary Dermal Irritation

870.2600	Dermal Sensitization	yes

yes

yes

yes

yes

yes	yes

yes

yes

yes

yes

yes

870.3100	Oral Subchronic (rodent)

870.3150	Oral Subchronic (nonrodent)

870.3200	28-Day Dermal

870.3250	90-Day Dermal

870.3465	90-Day Inhalation	yes

no

no

no

no	yes

yes

yes

--

no

870.3700a	Developmental Toxicity (rodent)

870.3700b	Developmental Toxicity (nonrodent)

870.3800	Reproduction	Yes

no

no	yes

yes

yes

870.4100a	Chronic Toxicity (rodent)

870.4100b	Chronic Toxicity (nonrodent)

870.4200a	Oncogenicity (rat)

870.4200b	Oncogenicity (mouse)

870.4300	Chronic/Oncogenicity	No

no

no

no

no	yes

--

yes

--

--

870.5100	Mutagenicity—Gene Mutation - bacterial

870.5300	Mutagenicity—Gene Mutation - mammalian

870.5375	Mutagenicity—Structural Chromosomal Aberrations

870.5xxx	Mutagenicity—Other Genotoxic Effects	Yes

Yes

Yes

No	yes

yes

yes

--

870.6100a	Acute Delayed Neurotox. (hen)	

870.6100b	90-Day Neurotoxicity (hen)

870.6200a	Acute Neurotox. Screening Battery (rat)

870.6200b	90 Day Neuro. Screening Battery (rat)

870.6300	Develop. Neuro	No

no

no

no

no

no	-

-

-

-

-

-

870.7485	General Metabolism

870.7600	Dermal Penetration	No

No	Yes

-

Special Studies for Ocular Effects

Acute Oral (rat)	

Subchronic Oral (rat)	

Six-month Oral (dog)		No

no

no

no	-

-

-

-



3.0	DATA GAP(S)  TC \l1 "3.0	DATA GAP(S) 

Based on the non-food use of linear alkylbenzene Sulfonate (LAS), as
well as the limited use as a house hold detergent, the database appears
to be adequate.  However, given the uncertainties in the monkey
inhalation toxicity study, the Agency requests the registrant to submit
a 90-day guideline inhalation toxicity study in the rat, with nose-only
exposure to the chemical of concern, not to a mixture of chemicals, so
the Agency can determine the specific response to inhalation exposure to
that chemical, rather than to a mixture of chemicals. 

4.0	HAZARD ASSESSMENT  TC \l1 "4.0	HAZARD ASSESSMENT 

4.1	Acute Toxicity  TC \l2 "4.1	Acute Toxicity 

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

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

Guideline No./ Study Type	MRID No.	Results	Toxicity Category

870.1100 Acute oral toxicity	Multiple	LD50 = range from 404 to over 5000
mg/kg 	III-IV

870.1200 Acute dermal toxicity	94032006	LD50 = 1200 mg/kg	II

870.1300 Acute inhalation toxicity	Open Literature (HERA 2004)	LC50 =
310 mg/m3	II

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 	Non-sensitizer

	* Tox record No.

4.2	Subchronic Toxicity  TC \l2 "4.2	Subchronic Toxicity 

Adequacy of data base for subchronic toxicity:  The data base for
subchronic toxicity is considered complete. No additional studies are
required at this time.  The major reviews by the WHO (1996), and HERA
(2004) report and/or summarize many subchronic studies via the oral
(gavage, feed, and drinking water), dermal, and inhalation routes.  Only
the critical studies or ones for which OPP has developed DERs over the
years are summarized here. 



90-Day Oral Toxicity – Rat

(Ikawa et al.1978; as cited in HERA, 2004).

LAS was administered for 2, 4, and 12 weeks to male rats (5/group) at a
single dose of 1.5% in the diet (750 mg/kg bw/day). LAS suppressed body
weight gain, and the relative liver weight was increased after 2 weeks
of LAS administration.  Serum biochemical examinations revealed
significant increases in ALP and GTP at each observation period and
significant decreases in cholesterol and protein in 4 weeks. Enzymatic
examinations of the liver revealed decreases in G6Pase and G6PDH and an
increase in isocitrate dehydrogenase (IDH) at each observation period.
Enzymatic examinations of the renal cortex revealed decreases in G6Pase
and 5'-nucleotidase at each observation period, an increase in LDH at 12
weeks, and an increase in IDH at 2 and 4 weeks.  Enzymatic examinations
in the renal medulla revealed a decrease in Na, K-ATPase, and an
increase in LDH at 12 weeks, a decrease in IDH at 2 weeks, and an
increase in IDH at 12 weeks.

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

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

Acceptable/Guideline.

870.3101         90-Day Oral Toxicity - Mouse

This study is not available in the database of this chemical; however, a
sub-chronic monkey study is available in the database.

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

Core Classification: ACCEPTABLE

870.3150	90-Day Oral Toxicity - Dog

This study is not available in the database of this chemical.

870.3200	21/28-Day Dermal Toxicity – Rat

This study is not available in the database of this chemical; however,
there were a 28-dermal study in the rabbit (Tox record No. 003441),
which was classified as “unacceptable” and an acceptable 30-day
study in guinea pigs summarized below.

Mathur et al. (1992). J Toxicol Cutan Ocular Toxicol, 11(1): 3-13. (as
cited in WHO 1996). 

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

90-Day Inhalation – Rat

This study is not available in the database of this chemical; however,
there is an acceptable, non-guideline sub-chronic monkey inhalation
study. 

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

Routine measurements included body weight, toxic signs, clinical
evaluation, chest radiograph, tuberculin skin test, pulmonary function
tests (3 different tests), hematoloqy, clinical chemistry, urinalysis,
intradermal and prick test, necropsy, and histopathology.  The NOEL is 1
mg/m3 detergent dust combined with up to 0.1 mg/m3 enzyme dust. The
detergent dust at 100 mg/m3 alone and with enzyme dust produced
mortality.  At least one animal in each group exposed to enzyme dust had
precipitating antibodies to the enzyme. There were no effects at any
level in total respiratory system flow resistance, diffusion capacity,
hematology, clinical chemistry, urinalysis, intradermal or skin-prick
challenge test results, and chest X-rays. 

In this published study, the detergent was dried and micronized to make
it respirable. However, it should be noted that most uses of this
detergent are in liquid form. 

The detergent dust alone at 100 mg/m3 (group 2) caused gross signs of
respiratory distress, pulmonary histopathological effects, and pulmonary
function impairment.  This impairment, measured by the nitrogen washout
method, was indicative of constricted small airways. 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 and decreased weight gain.  One animal in the
100 mg/m3 group (group 2) died, and a second was sacrificed in moribund
condition during the exposure period. .  Their deaths were considered
exposure-related according to necropsy and histopathologic observations.
 Acute effects (pulmonary edema, focal hemorrhaging, bronchiolitis) were
also seen in the lungs.

Gross clinical observations of noisy breathing, were consistent, and
correlated with subsequent pulmonary function and histopathologic
findings.  These clinical observations appeared to be related primarily
to the level of detergent dust.

Exposure-related histopathological alterations were seen, however, in
the lungs from all of the monkeys in Groups 2. They were found in the
respiratory bronchioles and proximal alveoli. These alterations were
characterized by the infiltration of mononuclear macrophages,
lymphocytes, and in some instances, polymorponuclear graculocytes into
the walls of the respiratory bronchioles.  The walls of the respiratory
bronchioles were moderately to markedly fibrosed, and there was a
diffuse nonsuppurative alveolities in the proximal alveoli adjacent to
respiratory broncioles.  The nonsuppurative alveolitis was characterized
by an infiltration of mononuclear macrophages and lymphocytes into the
alveolar walls and lumen.  A moderate to marked fibrosis of the alveolar
walls was evident in affected alveoli, as was a moderate pneumocyte
hyperplasia.  In many monkeys the bronchioles were constricted and there
were moderate hypertrophy and hyperplasia of the bronchiolar epithelium.
Basal cell hyperplasia and focal squamous metaplasia were seen in the
tracheas of monkeys in Groups 2.

Core Classification: ACCEPTABLE, NON-GUIDELINE. This study is considered
a data gap.

4.3	Prenatal Developmental Toxicity  TC \l2 "4.3	Prenatal Developmental
Toxicity 

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

870.3700a Prenatal Developmental Toxicity Study – Rat

Teratology - rat, mouse, rabbit, MRID NO. 43498426 (“Palmer Part
I”).

Randomized groups of 20 CD-1 pregnant mice, 20 CD rats, and 13 NZW
rabbits were housed individually and fed appropriate diets ad libitum.
Day 0 of gestation was judged by a vaginal plug in rats and mice and
coitus in rabbits. Dosing began on day 6 and continued daily up to day
15 for mice and rats and day 18 for rabbits. The test material was
supplied by Lion fat and Oil Co., Led, Tokyo. Doses were 0, 0.2, 2.0,
300 and 600. mg/kg BW. Animals were observed daily and weighed
regularly. At termination (Days 17, 20, and 29 for mice, rats, and
rabbits), the uteri were immediately dissected and contents examined to
determine implantations, viable young, embryonic deaths (abortion or
resorption sites). Ovaries were examined and the number of corpora lutea
counted for rats and rabbits. Fetuses were weighed and externally
examined for abnormalities. With rabbits, the fetuses were immediately
dissected and examined for visceral abnormalities. Sex was determined by
gonadal inspection and carcasses preserved in alcohol for subsequent
clearing, staining. with alizarin, and skeletal examination. With mice
and rats, following weighing and external examination, one third were
fixed in Baum’s solution

for free hand sectioning for visceral abnormalities and the remaining
two-thirds fixed in alcohol, cleared, stained with alizarin and examined
skeletally.

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

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

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

Core Classification: ACCEPTABLE

Dermal Developmental Toxicity — Rat, Rabbit, Mouse MRID: 43511403. 
(Palmer Part III).

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

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

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

The moderate maternal toxicity of LAS, 0.3% in the mouse correlated with
a higher incidence of embryonic deaths and lower litter size but only
the former differed significantly from the corresponding control value.

The incidences of major malformations, minor visceral or skeletal
anomalies, and skeletal variants provided no conclusive evidence of
specific teratogenicity even at maternally toxic dosages.

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

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

Mouse-Developmental

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

Embryos were flushed from the oviducts and uterus with Whitten medium.
After examination, the embryos were then. cultivated at 37oC in medium
equilibrated with a 5% carbon dioxide, 5% oxygen, and 90% nitrogen gas
mixture. 

A 2.0% dermally applied dose of LAS retarded development and interrupted
cleavage of eggs. Significantly higher numbers of embryos were found to
be deformed in the LAS group in comparison to controls, and most of
these embryos were in the morula stage, whereas they were mostly in the
late blastocyst stage in controls.

Core Classification: ACCEPTABLE

870.3700b Prenatal Developmental Toxicity Study – Rabbit

This study is included with section 870.3700a.

4.4	Reproductive Toxicity  TC \l2 "4.4	Reproductive Toxicity 

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

870.3800 Reproduction and Fertility Effects – Rat

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

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

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

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

Core Classification: ACCEPTABLE 

4.5	Chronic Toxicity  TC \l2 "4.5	Chronic Toxicity 

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

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

Groups of 8 or 9 male/females mice were given diets containing LAS at
concentrations of 0.6 and 1.8% (corresponding to 500 and 1000 mg/kg
bw/day) or drinking water containing LAS at

concentrations of 0.07%, 0.2% and 0.6% for 9 months (corresponding to
100, 250, 600 mg/kg bw/day for males and to 100, 250, 900 mg/kg bw/day
for females) (Yoneyama et al., 1976 as cited in HERA, 2004). Control
groups were used.

In the mice given 500 mg/kg bw/day via the food, body weight gain was
not suppressed, but the

weight of the liver increased in male and female mice. Enzymatic
examinations revealed significant decreases in LDH of the liver and in
acid phosphatase of the kidneys in the male mice. Thus, there was no
NOAEL in this study since these effects were seen at the lowest dose of
500 mg/kg/d.

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

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

  

870.4100b Chronic Toxicity - Dog

	This study is not available in the toxicology database of this
chemical.

4.6	Carcinogenicity  TC \l2 "4.6	Carcinogenicity 

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

870.4200a Carcinogenicity Study – rat

Takahasi (MRID 43498420) performed an experiment to assess the ability
of SDDBS to affect the induction of gastric tumors by 4-NQO in male
Wistar rats. Sixty-four male rats of the Motoyania strain and 97 male
Wistar rats were used in the study under the following regimen:

Group I (79 rats): 1 mg 4-NQO and 80 mg SDDBS 2-3 times per week for 18
weeks

Group 1’ (17 rats): same as Group I, but fasted 12 hours prior to
dosing

Group II (37 rats): 4-NQO only as per Group ‘1

Group III (28 rats): SDDBS only as per Group I 

The experiment lasted 560 days and all rats dying on study or terminally
sacrificed, were necropsied and examined histologically for
gastrointestinal tumors.  In Groups I and I‘, the presence of SDDBS-
shifts the incidence of benign papillomas to malignant papillomas of the
forestomach and the incidence of adenocarcinoma and sarcoma of the
stomach were increased in comparison to Group II with only 4- NQO. The
administration of SDDBS by itself has no effect. on gastric tumors
(Group III). The study authors concluded .that the increased
carcinogenicity produced by SDDBS was due to the better uptake of 4-NQO
via LAS’S surfactive/detersive effects on the protective mucous
barrier which is normally found in the glandular stomach and other
gastric compartments of the rat. The effect of SDDBS was physical rather
than chemical in promoting the increased tumorigenicity.

In a similar study by the same investigators, (Takahasi, MRID 43498419)
Motoyama male rats were divided into three groups and gavaged with the
following regimen;

Group I (37 rats): 1 mg 4-NQO + 80 mg SDDBS + 20 mg ethanol in a 1 ml
gavage for 18 weeks.

Group II (13 rats): 4-NQO and ethanol for 18 weeks. 

Group III (13 rats): SDDBS + ethanol for 18 weeks.

Again, the experiment lasted 560 days and all rats, dying on study or
terminally sacrificed, were necropsied and examined histologically for
gastrointestinal tumors.

Survival: Mortality was 59% in Group I, 31% in Group II and 23% in Group
III.

Tumors:

Group III - no gastric tumors -

Group II - 9 benign papillomas of forestomach

Group 1 - 8 benign papillomas of forestomach, 2 malignant papillomas of
forestomach, 1 hemangiosarcoma of forestomach. In glandular stomach, 2
adenocarcinomas, 1 hemangiosarcoma, 1 hemangioma, 5 squamous cell
carcinomas and 2 rats exhibited atrophic gastritis.

The increased toxicity in Group I produced increased mortality and
increased numbers of malignant tumors. The role of SDDBS in the
tumorigenesis of 4—NQO was to promote increased absorption o 4—NQO
through the forestomach and glandular stomach. 

Core Classification: ACCEPTABLE

Carcinogenicity Study - rat

MRID No. 43498416

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

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

870.4200b Carcinogenicity (feeding) - Mouse

This study is not available in the toxicology database of this chemical.

4.7	Mutagenicity  TC \l2 "4.7	Mutagenicity 

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

	Gene Mutation

Guideline 870.5100 

study type: Gene Mutation - bacterial  

MRID No. 43498429

Classification: Literature, acceptable	Negative at cytotoxic levels or
limit concentrations (both with and without S-9 metabolic activation)
when tested with Salmonella typhimurium - TA 98 and TA 100 strains.





	Cytogenetics

Guideline # 870.5385 

study type: Structural Chromosomal Aberrations 

MRID No. 43498428

Classification: Literature, acceptable	LAS were administered to rats in
the diet for 90-days at doses of 0, 280, or 565 mg/kg/d.  All test
preparations were negative for increased chromosomal damage over
controls.





	Other Genotoxicity

Guideline # 870.5300	

study type: In Vitro cell transformation

MRID No. 43498429 

Classification,: Literature, acceptable	LAS tested negative in Syrian
Hamster Ovary (SHE) cells at up to 50 micrograms/plate.  



4.8	Neurotoxicity  TC \l2 "4.8	Neurotoxicity 

Adequacy of data base for Neurotoxicity:  These studies are not
available or required at this time.

However, there’s no evidence in the literature to indicate any
neurotoxic effects of LAS in humans or laboratory animal.

Metabolism

  TC \l2 "4.9	Metabolism 

Adequacy of data base for metabolism: The data base for metabolism is
considered to be complete. No additional studies are required at this
time.

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

Metabolism – Rat

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

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

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

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

Core Classification: ACCEPTABLE 

Metabolism – Monkey

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

For the subcutaneous studies, each- animal, following 2-3 weeks between
dose levels, received single subcutaneous doses of C14 LAS (SDDBS; 25
microcuries) at levels of 0.1, 0.5 and 1.0 mg/kg. Blood, urine, feces
and cage washing samples were taken for mass balance, metabolite
identification and plasma kinetics. Following 2-3 weeks after the last,
single subcutaneous dose, each monkey received 7 consecutive daily
subcutaneous doses of 1.0 mg/kg/day of C14 LAS. Animals were sacrificed
after the last dose and tissue. samples taken for direct combustion.

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

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

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

Core Classification: ACCEPTABLE

870.7600	Dermal Absorption - Rat

No dermal absorption studies are available in the toxicology database.

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

	

Special/Other Studies: N/A 

5.0	TOXICITY ENDPOINT SELECTION  TC \l1 "5.0	TOXICITY ENDPOINT SELECTION


See Section 9.2 for Endpoint Selection Table.

5.2	Dermal Absorption:  TC \l2 "5.2	Dermal Absorption  

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

     Classification of Carcinogenic Potential: 

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

6.0	FQPA CONSIDERATIONS  TC \l1 "6.0	FQPA CONSIDERATIONS 

Special Sensitivity to Infants and Children

Based on the available hazard data, it doesn’t appear that LAS
exposure in laboratory animal studies results in any special sensitivity
to the young.  Therefore, the FQPA factor may be reduced to 1X.

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

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

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

There is no need for a special FQPA factor because the mid-dose level of
50 mg/kg/d (NOAEL for offspring effects) in the Buehler study is the
basis for the chronic RfD of 50 mg/kg/d.  Thus, the chronic hazard value
is based on slight pup effects and is protective of laboratory animals
of all ages in this hazard assessment.

  TC \l2 "6.1	Special Sensitivity to Infants and Children 

6.2	Recommendation for a Developmental Neurotoxicity Study  TC \l2 "6.2
Recommendation for a Developmental Neurotoxicity Study 

	A DNT is not required because there is no evidence of either
neurotoxicity or susceptibility to the young following LAS exposure to
laboratory animals.  TC \l2 "5.3	Classification of Carcinogenic
Potential 

7.0	OTHER ISSUES: N/A 



8.0	REFERENCES  TC \l1 "8.0	REFERENCES  in MRID order

MRID No.	Guideline No./Study Type	Source

Multiple studies	870.1100 Acute oral toxicity	Tox Oneliner

94032006	870.1200 Acute dermal toxicity	Tox Oneliner

Open Literature	870.1300 Acute inhalation toxicity	Open Literature (HERA
2004)

0033443*	870.2400 Acute eye irritation	Tox Oneliner

003444*	870.2500 Acute dermal irritation	Tox Oneliner

N/A	870.2600 Skin sensitization	Open Literature

N/A	870-3100 Subchronic Oral Toxicity – Rat	Ikawa et al.1978.
HERA-2004)

N/A	870-3100 Subchronic Oral Toxicity – Rat	Ito, et al. (1978) J. Med.
Soc. Toho Univ. 25: 850-875.

43498413	Subchronic Oral Toxicity – Monkey	HERA-2004

N/A	21/28-Day Dermal Toxicity – Guinea Pig

	Mathur et al. (1992). J Toxicol Cutan Ocular Toxicol, 11(1): 3-13. (WHO
169). 

43498403	Subchronic Inhalation Toxicity – Monkey	HERA-2004

43498426	870.3700a Prenatal Developmental Toxicity Study – Rat, Mouse,
Rabbit, 	Palmer et al. Part I, HERA-204

43511403	Dermal Developmental Toxicity — Rat, Rabbit, Mouse 	Palmer et
al. Part III, HERA-2004

43498424 & 43498425	Mouse-Developmental

	43498416	870.3800 Reproduction and Fertility Effects – Rat



870.4100a Chronic Toxicity – Rat	Yoneyama et al.,1976

(see tox profile table)

	870.4100b Chronic Toxicity – Mouse	Yoneyama et al.,1976

(see tox profile table)

43498420 & 43498419	870.4200a Carcinogenicity Study – rat

	43498416

	870.4200a Carcinogenicity Study – rat

	43498429	 870.5100  Gene Mutation - bacterial  

	43498428	870.5385 Structural Chromosomal Aberrations 

	43498427	870.5300 In Vitro cell transformation 

	MRID No.	Guideline No./Study Type	Source

43498431	  Metabolism – Rat

	43498410	Metabolism – Monkey 



 Isolated human skin preparations	Howes,1975

(see tox profile table)

* Tox record No.

Other Sources:

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

Human and Environmental Risk Assessment (HERA).  2004.  LAS – Linear
Alkylbenzene Sulfonates (CAS No. 68411-30-3).    

9.0APPENDICES  TC \l1 "9.0APPENDICES 

Tables for Use in Risk Assessment

Toxicity Profile Summary Tables

  TC \l2 "9.1	Toxicity Profile Summary Tables 

9.1.1	Acute Toxicity Table  TC \l3 "9.1.1	Acute Toxicity Table  - See
Section 4.1

Subchronic, Chronic and Other Toxicity Tables:

Guideline No./

Study Type	MRID No./

Reference Information/

Study Classification	Dosing and Animal Information	Results

Subchronic Toxicity

870.3100

Oral Subchronic (rodent)	Bornmann et al (1963) Study of a Detergent
Based on Dodecylbenzene Sulfonate. Fette Seifen Anstrichm, 65 (10):
818-824.  (EHC 169)

Open Literature	0.01% of a preparation containing 51% LAS was
administered in the drinking water for 100 weeks

Rats (60/sex)

Purity: Not Reported	No detrimental effects on body weight and no
pathological effects, including tumors, were reported

870.3100

Oral Subchronic

(rodent)	Ikawa et al., (1980)/

Ann. Rep. Tokyo Metrop. Res. Lab. Public Health.  29(2):  51-54(Z). 
1978 (in Japanese, see WHO, 1996 and HERA, 2004).

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

Male rats (five/group)

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

870.3100

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

Open Literature

	Administration by oral gavage at doses of 0, 155, 310, or 620 mg/kg/day
(LAS-Mg) and 125, 250, and 500 mg/kg/day (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



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 Sulfonate (LAS) in Rhesus Monkeys I.
Simultaneous Oral and Subcutaneous Administration for 28 Days. Toxicol.
Appl. Pharmacol. 11: 245-250.  (HERA)

Acceptable

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

subcutaneously (sc). Control groups were used.

Rhesus Monkey (3/sex/dose), 18-36 months old

Purity: Not Reported

	At 300 (po) and 1.0 (sc) mg/kg bw/day, the monkeys

vomited frequently and usually within 3 hours of administration. An
increased frequency of loose or liquid faeces was recorded for animals
receiving 150 (po) and 0.5 (sc) mg/kg bw/day. These effects

are probably related to the inherent irritative effects of LAS rather
than to its systemic toxicity.

Fibrosis of the injection sites was found among the entire test group,
the incidence and severity being

dose related. Ophthalmoscopy, laboratory examination of blood and urine,
organ weight analysis and

histopathological investigation did not detect any further
treatment-related responses.

The LOAEL is 150 mg/kg bw/day (po) + 0.5 mg/kg bw/day (sc) based on an
increase in liquid feces and the NOAEL is 30 mg/kg/d

870.3200

21-Day Dermal	Mathur et al. (1992) Effect of Dermal Exposure to LAS
Detergent and HCH Pesticide in Guinea Pigs: Biochemical and
Histopathologic Changes in Liver and Kidney. J Toxicol Cutan Ocular
Toxicol, 11(1): 3-13. (WHO 1996)

Open Literature	A solution of LAS in distilled water equivalent to 60
mg/kg bw was applied to a 4-cm2 area of clipped dorsal skin daily for 30
days

12 Guinea Pigs

Purity: Not Reported	The activities of B-glucuronidase, gamma- glutamyl
transpeptidase, 5-nucleotidase, and sorbitol dehydrogenase were
increased in liver and kidney.  Lipid peroxidation was increased in the
kidney but not in liver, and the glutathione content was unchanged in
both organs.  Extensive fatty changes were found in hepatic lobules,
with dilation of sinusoids; tubular lesions were found in the kidney,
predominantly in the proximal and distal portions.



870.3200

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

Unacceptable

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

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

Purity: 10% 	NOEL: > 200 mg/kg/d

870.3465

90-Day Inhalation	MRID No. 43498403 Coate et al. (1978) Respiratory
Toxicity of Enzyme Detergent Dust.  Toxicol. Appl. Pharmacol., 45:
477-496.

Acceptable

Non-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

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 Toxicity (rodent)	MRID 43498424 and 43498425

Nomura, T et al. (1980) The Synthetic Surfactants AS and LAS Interrupt
Pregnancy in Mice.  Life Sciences, 26: 49-54.  (HERA)

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

Acceptable

Guideline	LAS (0.1 ml ) was applied at a concentration of 20% to the
dorsal skin of pregnant mice during the pre-implantation period  twice a
day from day 0 to day 3 of pregnancy

Female  ICR/Jcl Mouse, 

9-10 weeks old

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

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

870.3700a

Developmental Toxicity (rodent)	MRID 43498426

Palmer et al. (1975) Assessment of the Teratogenic Potential of
Surfactants, (Part I), Toxicology 3: 91-106.

Acceptable

Guideline	LAS was administered by gavage on days 6-15 of pregnancy in
rats and mice and days 6-18 of pregnancy in rabbits at doses of 0.2, 2,
300, and 600 mg/kg bw/d 

20 CD Rats, 20 CD-1 Mice, and 13 New Zealand White Rabbits  

Purity: 17%	NOAEL (rat - maternal): 300 mg/kg bw/d

NOAEL (mouse - maternal): 2.0 mg/kg bw/d (However, there is a large
difference between this dose and the next highest dose of 300 mg/kg
bw/d, this study does not allow determination of a reliable maternal
NOAEL for mice) 

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

NOAEL (rat - developmental): 300 mg/kg bw/d 

NOAEL (mouse - developmental): 2.0 mg/kg bw/d

NOAEL (rabbit - developmental): 2.0 mg/kg bw/d

NOAEL (rat - fetal): 600 mg/kg bw/d

NOAEL (mouse - fetal): 300 mg/kg bw/d  (Due to a high mortality rate of
parent animals, no assessment was possible at 600 mg/kg bw/d)

NOAEL (rabbit - fetal): could not be determined

870.3700a

Developmental Toxicity (rodent)	MRID 43511403

Palmer, et al. (1975) Assessment of the Teratogenic Potential of
Surfactants, (Part III) - Dermal Application of LAS and Soap. 
Huntingdon Research Centre, Huntingdon, Great Britain.  Study No. DDBSA
JV-RP4-029.  Toxicology 4: 171-181.

Acceptable

Guideline	LAS was administered percutaneously to shaved skin at
solutions of 0.03%, 0.3%, and 3% during pregnancy on days 2-13 in mice,
2-15 in rats, and 1-16 in rabbits.  Dosages employed were 0.5 ml/rat or
mouse/day and 10 ml/rabbit/day 

CD-1 Mice (20/group), CD Rats (20/group), N2W Rabbits (13/group)

Purity: 0.03%, 0.3%, and 3%	LOEL (maternal toxicity, mice): 0.3% (50
mg/kg/d) 

LOEL (maternal toxicity, rats): 3.0% (60 mg/kg/d)

LOEL (maternal toxicity, rabbits): 0.3% (9.0 mg/kg/d)

NOEL (maternal toxicity, mice): 0.03% (5.0 mg/kg/d)

NOEL (maternal toxicity, rats):  0.3% (6.0 mg/kg/d)

NOEL (maternal toxicity, rabbits): 0.03% ((0.9 mg/kg/d)

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

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

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

NOEL (developmental toxicity): 0.03% (5.0 mg/kg/d)

NOEL (developmental toxicity): 0.3% (6.0 mg/kg/d)

NOEL (developmental toxicity): 0.3% (9.0 mg/kg/d)

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

Moderate maternal toxicity was observed among mice treated with LAS,
0.3% and mild maternal toxicity in rats receiving LAS 3% or soap 30% and
rabbits receiving LAS 0.3%.

Effects on litter parameters were dose-dependent,  causing marked
maternal toxicity in mice, the principal  higher fetal loss,  reduction
in viable litter size. 

LAS at 3% showed marked maternal toxicity in the rabbit

The moderate maternal toxicity of LAS, 0.3% in the mouse correlated with
a higher incidence of embryonic deaths and lower litter size but only
the former differed significantly from the corresponding control value.



870.3700a

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

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

F Mouse

Purity: Not Reported	NOAEL (maternal): 110 mg/kg bw/d

No abnormalities were seen in the dam or foetuses.

870.3700a

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

Open Literature	LAS was administered by gavage at doses of 10, 100, and
300 mg/kg bw/d at day 6 through 15 of gestation

ICR-SLC Mouse (25-33/dose)

Purity: Not Reported	LOAEL (maternal): 10 mg/kg bw/d

NOAEL (fetuses): 300 mg/kg bw/d

1.  Marked maternal and embryonic toxicities, such as maternal death,
premature delivery, total litter loss and high fetal death rate, were
observed at 300 mg/kg group.

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

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

870.3700a

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

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

Mouse (13-14/group) 

Purity: not reported	NOAEL (maternal): 40 mg/kg bw/d

NOAEL (fetuses): 400 mg/kg bw/d

At 400 mg/kg bw/day, the pregnancy rate was 46.2% compared to 92.9% in
the controls. There was no

increase in malformations. Although no information on maternal toxicity
is available, it appears

likely that maternal toxicity was present at the high dose group.

870.3700a

Developmental Toxicity (rodent)	Tiba et al. (1976) Effects of LAS on
Dam, Fetus, and Newborn Rat. J. Food Hyg. Soc. Jpn. (Shokuhin Eiseigaku
Zassh) 17(1): 66-71.  (HERA)

Open Literature	LAS was administered in the diet at doses of 80 and 780
mg/kg bw/d from day 0 to 20 of gestation 

F Rat (16/dose) 

Purity: Not Reported	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 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 (rodent)	Taniguchi et al. (1978) Results of
Studies on Synthetic Detergents.  Tokyo, Science and Technology Agency,
Research and Coordination Bureau, pp. 18-54.  (WHO 1996)

Open Literature	LAS were applied to the dorsal skin of rats three times
per week at doses of 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.	Treatment had no effect on organ weights or
histopathological appearance, and there was no evidence of toxicity or
carcinogenicity.

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.  (HERA)

Acceptable

Guideline	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)

870.4200a

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

Open Literature	LAS was administered in the drinking water at the dose
of 200 mg/kg bw/d  

62 M/F Wistar Rat

Purity: 38.74% a.i.	The administration of LAS had no effect on the
intake of water, mortality, body weight gain, or general condition.  In
pathological examinations, looseness, atrophy, and fatty change of the
hepatic cells in the liver were found in the experimental control group
at 6 months, together with significant increases in GOT, GTP and
bilirubin.  In hematological examinations no effects due to LAS were
observed.

870.4200a

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

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

Open Literature	LAS was administered in the feed at a concentration of
0.04, 0.16, and 0.60% for  24 months or lifespan

Wistar Weanling Rat (15/sex/dose) 

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

870.4200a

Oncogenicity (Rat)	MRID 43498420

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

Acceptable

Guideline	For 560 days; Group I (79 rats): 1 mg 4-NQO and 80 mg SDDBS
2-3x per week for 18 weeks; Group I' (17 rats): same as Group 1, but
fasted for 12 hours prior to dosing,; Group II (37 rats):  1 mg 4-NQO
only; Group III (28 rats): 80 mg SDDBS only

 97 M Wistar Rats

Purity: Not Reported	In Groups I and I', the presence of SDDBS shifts
the incidence of benign papillomas to malignant papillomas of the
forestomach and the incidence of adenocarcinoma and sarcoma of the
stomach were increased in comparison to Group II with only 4-NQO.  The
administration of SDDBS by itself has no effect on gastric tumors (Group
III).  The study authors concluded that the increased carcinogenicity
produced by SDDBS was due to the better uptake of 4-NQO via LAS's
surfactive/detersive effects on the protective mucous barrier which is
normally found in the glandular stomach and other gastric compartments
of the rat.  The effect of SDDBS was physical rather than chemical in
promoting the increased tumorigenicity.

870.4200a

Oncogenicity (Rat)	MRID 43498419

Takahasi et al. (1970) Effect of 4-Nitroquinoline-1-Oxide with
Alkylbenzenesulfonate on Gastric Carcinogenesis in Rats.  GANN: 61,
27-33.

Acceptable

Guideline	Rats were divided into three groups and gavaged with the
following regimen for 560 days: Group I (37 rats) - 1 mg 4-NQO + 80 mg
SDDBS + 20 mg ethanol in a 1 ml gavage for 18 weeks; Group II (13 rats)
- 4-NQO and ethanol for 18 weeks; Group III (13 rats) - SDDBS + ethanol
for 18 weeks 

64 M Motoyama Strain Rat

Purity: Not Reported	Survival: Mortality was 59% in Group I, 31% in
Group II, and 23% in Group III

Tumors: Group III - no gastric tumors; Group II - 9 benign papillomas of
forestomach; Group I - 8 benign papillomas of forestomach, 2 malignant
papillomas of forestomach, 1 hemangiosarcoma of forestomach.  In
glandular stomach, 2 adenocarcinomas, 1 hemangiosarcoma, 1 hemangioma, 5
squamous cell carcinomas, and 2 rats exhibited atrophic gastritis.

The increased toxicity in Group I produced increased 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-Nitrosoguanidine with Various Kinds of Surfactant in
the Glandular Stomach of Rats.

Acceptable

Guideline	SDDBS was administered to 5 groups of rats: (I) 13 rats
received 0.1g of MNNG + 4000 mg Tween 60 per L of drinking water for 36
weeks; (II) 16 rats received 0.1 g MNNG + 2000 mg nonipol per L of
drinking water for 36 weeks; (III) 15 rats received 0.1 g of MNNG + 1000
mg branched ("hard") SDDBS per L of drinking water for 63 weeks; (IV) 10
rats received 0.1 g MNNG + 1000 mg of linear ("soft") SDDBS per L of
drinking water for 63 weeks; (V) 14 rats received o.1 g MNNG per L of
drinking water for 63 weeks

M Wistar Rats 

Purity: Not Reported	Survivial was 100% in Groups I, III, and IV, and
93% and 94% in Groups V and II, respectively.  

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

870.4200a

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

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

M Wistar Rat (20/group)

Purity: Not Reported	There were no changes due to the administration of
LAS in regard to growth, mortality, the weight of major organs, or
histopathological findings

Mutagenicity

870.5100 Bacterial reverse mutation test	Huls, Report No. AM-93/12,
Unpublished data, 1993.  (As cited in HERA-2004)

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

Salmonella typhimurium, strains TA 98, TA 100, TA 1535, TA 1537, and TA
1538 

Purity: Not Reported	Negative results

870.5100 Bacterial reverse mutation test	MRID 43498429

Inoue et al. (1980)  Studies of In Vitro Cell Transformation and
Mutagenicity by Surfactants and other Compounds, Food. Cosmet. Toxicol
18: 289-296.  (HERA)

Acceptable

Guideline	SDDBS was tested at cytotoxic levels or limit concentrations
of 2,000-30,000 ug/plate for 2 days (Salmonella) or 8 days (SHE) 

Strain: Salmonella typhimurium - TA 98 and TA 100 cells and Embryonic
Syrian Golden Hamster cells (SHE) 

Purity: Not Reported	Negative (both with and without S-9 metabolic
activation)

870.5100 Bacterial reverse mutation test	Sunakawa et al. (1981) Studies
on the Mutagenicity of Surfactants Following Activation with Various
Liver Homogenates (S-9) and Mutagenicity in the Presence of Norharman,
Hyg. Chem. (Eisei Kagaku) 27(4): 204-211, See: WHO, 1996.

Open Literature	LAS was tested at up to 500 ug/plate

Salmonella typhimurium 

Purity: Not Reported	Negative Results

870.5300

In Vitro mammalian cell gene mutation test	Inoue, K. et al. (1977)
Osaka-furitsu Koshu Eisei Kenkyusho Kenkyu Hokoku, Shokuhin Eisei Hen 8:
25-8.  (HERA)

Open Literature	Sodium alkylbenzenesulfonate was added to culture at
62.5 ug/ml and 125 ug/l 

Hamster Lung Cell

Purity: Not Reported	At 62.5 ug/ml: induced cell mutation, no effect on
sister chromatid exchange

At 125 ug/ml: destroyed the cells completely

870.5300	

 In Vitro cell transformation

	MRID No. 43498427 

K. Inoue et al (1980)

Food Cosmetic Toxicol.

18:289-296

Acceptable

Open Literature,	Duplicate primary cultures of embryonic SHE and
Salmonella typhimurium strain TA 98 and TA 100 cells were exposed to
SDDBS and positive and negative controls for 8 days.	SDDBS was negative
for transformation up to cytotoxic levels and did not induce mutation in
either strains of Salmonalla when allplied up to cytotoxic levels or
limit concentration of 2000-3000 ug/plate.

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

870.5385

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

Open Literature	LAS was administered at doses of 200, 400, and 800 mg/kg
bw/d by gavage for 1 and 5 days

M Mouse

Purity: Not Reported	There was no significant difference in the
incidence of chromosomal aberrations between any of the groups

870.5385

Mammalian bone marrow chomosomal aberration test	Inoue, K. et al. (1977)
In Vivo Cytogenetic Tests of Some Synthetic Detergents in Mice.  Ann Rep
Osaka Prefect Inst Public Health, 8: 17-24.  (HERA)

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

M ICR:JCL Mouse

Purity: Not Reported	There was no significant difference between any of
the groups given LAS and the negative control group in the incidence of
chromosomal aberrations

870.5385

Mammalian bone marrow chomosomal aberration test	MRID 43498428

J. Hope (1977) Absence of Chromosome Damage in the Bone Marrow of Rats
Fed Detergent Actives for 90 Days.  Mutation Research, 56: 47-50.

Acceptable

Guideline	SDDBS was administered in the diet for 90 days at 0, 280, and
565 mg/kg bw/d 

Colworth/Wistar Weanling Rat (6/sex/dose)

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

870.5385

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

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

Male Rat and Male Mouse

Purity: Not Reported	There were no significant differences in the
incidences of chromosomal aberrations between the experimental and
control groups

870.5395

Mammalian erthrocyte micronucleus test	Kishi et al. (1984) Effects of
Surfactants on Bone Marrow Cells, Bull. Kanagawa Public Health Lab. 14:
57-58.  (HERA)

Open Literature	LAS was administered as a single intraperitoneal
injection at a dose of 100 mg/kg bw 

3 M ddY Mice

Purity: Not Reported	There were no differences in the incidences of
polychromatic erythrocytes with micronuclei in the bone marrow cells
between the treated group and the control group

870.5395

Mammalian erthrocyte micronucleus test	Koizumi et al. (1985)
Implantation Disturbance Studies with LAS in Mice, Arch. Environ.
Contam. Toxicol. 14: 73-81.  (HERA)

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

Pregnant ICR Mice

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

870.5450

Rodent dominant lethal assay	Masubuchi MA et al. (1976) Cytogenetic
Studies and Dominant Lethal Tests with Long Term Administration of
Butylated Hydroxytoluene (BHT) and Linear Alkylbenzene Sulfonate (LAS)
in Mice and Rats.  Ann Rep Tokyo Metrop Res Lab Public Heath, 27(2):
100-104.

(HERA)

Open Literature	A diet containing 0.6% LAS at 300 mg/kg bw/d was
administered to mice for 9 months. Each of the male mice was then mated
with two female mice that had not been given LAS, and 11 of the 14
females became pregnant.  The pregnant mice were laparotomized on day 13
of gestation

7 M ICR:JCL Mice 

Purity: Not Reported	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.

Metabolism

870.7485 General Metabolism	MRID 43498410

Creswell et al. (1978) Toxicology Studies of Linear Alkylbenzene
Sulfonate (LAS) in Rhesus Monkeys II.  The Disposition of C14-LAS After
Oral or Subcutaneous Administration.  Toxicology, 11: 5-17.

Acceptable

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

2 M/2 F Rhesus Monkeys

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

870.7485 General Metabolism	Lay JP, et al. (1983) Toxicol. Letters 17
(1-2): 187-192

Open Literature	(14)C-labeled sodium dodecylbenzenesulfonate was
administered daily in the diet at a concentration of 1.4 mg/kg for 5
weeks

M Rat

Purity: not reported	From a total uptake of 1.213 + or - 0.08 mg/animal
of DBS, 81.8% was excreted during the dosing period: 52.4% in feces and
29.4% in urine.  Low levels of (14)C-DBS-derived residues were detected
in all tissues analyzed on day 35 of the study.  Following 1 week on a
normal diet, only 7.8% of the nominally stored amount of (14)C was found
in the excreta.

870.7485 General Metabolism	Sunakawa et al. (1979) Yakuzaigaku 39 (2):
59-68

Open Literature	Sodium-para-dodecylbenzenesulfonate 

Rat

Purity: Not Reported	Blood levels were max at 2 hr, negligible at 48 hr

Excretion rate of radioactive label was 99.4% after 48 hr

870.7485 General Metabolism	The Royal Society of Chemistry. (1981)
Foreign Compound Metabolism in Mammals. Volume 6: A Review of the
Literature Published during 1978 and 1979. London: The Royal Society of
Chemistry, p.354.

Open Literature	(35)S-labeled sodium dodecylbenzenesulfonate was
administered as a single oral dose 

Rat

Purity: Not Reported	Rats excreted 64% and 24% of the dose in urine and
feces, respectively

870.7485 General Metabolism	The Royal Society of Chemistry. (1981)
Foreign Compound Metabolism in Mammals. Volume 6: A Review of the
Literature Published during 1978 and 1979. London: The Royal Society of
Chemistry, p.354.	Repeated doses of (14)C-labeled alkylbenzenesulfonate
were orally administered 

Rhesus Monkey

Purity: Not Reported	Radioactivity did not accumulate in the tissues

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
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	Ringer's bicarbonate (containing sodium lauryl benzene
sulfonate) at 0.5 ml/min was used to perfuse a 10 cm length of jejunal
segment for 150 minutes; equilibrated for 30 minutes and then the
perfusates were collected in 30 minute aliqouts for 120 minutes

M Wistar Rat

Purity: 0.5%	Alkaline phosphatase was released by an increase of 15-fold
in comparison to Ringer's alone (controls without added sodium lauryl
benzene sulfonate) and 3-7 times greater than other surfactants tested
in Ringer's.  The authors conclude that SDDBS has an exfoliative effect
on the intestinal brush border

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

Open Literature	Solutions of various concentrations of LAS were mixed
with red blood cells from rabbits at room temperature for 3 hours

Rabbit Red Blood Cell

Purity: Not Reported	The 50% haemolytic concentration of LAS was 9
mg/litre

Other	Samejima Y (1991) Effects of Synthetic Surfactants and Natural
Soap on the Development of Mouse Embryos In Vitro and the Fertilizing
Capacity of Mouse and Human Sperm.  J Osaka Univ Med Sch, 3 (12):
675-682.  (EHC 169)

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

F B6C3F1 Mouse Egg 

Purity: Not Reported	Concentrations of LAS less than 0.025%: Eggs
exposed for 1 hr, washed, and then cultured for 5 days developed
normally to the blastocyst stage

Concentrations of LAS higher than 0.03%:  The eggs did not develop
beyond the one-cell stage

With continuous exposure to LAS for five days, a concentration of 0.01%
slightly impaired development to the blastocyst stage, and 0.025%
prevented development to the one-cell stage

Other	Takahashi et al. (1974) Inhibition of Thrombin by Linear
Alkylbenzene Sulfonate (LAS).  Ann Rep Tokyo Metrop Res Lab Public
Health, 25: 637-645.  (HERA)

Open Literature	Purified LAS at various concentrations were added to 10
ul of plasma from rats and prothrombin time was determined

M Rat

Purity: Not Reported	Prothrombin time was prolonged; the 50% inhibitory
concentration was about 0.6 mmol/litre.  When LAS at various
concentrations were added to a mixture of 1% fibrinogen and thrombin,
the time of formation of a mass of fibrin was prolonged by inhibition of
thrombin activity.  The 50% inhibitory concentration was about 0.05
mmol/litre.

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

Open Literature	The haemolytic action of LAS was investigated by mixing
red blood cells from rabbits with solutions of LAS at concentrations of
1-1000 mg/litre at 38 C for 30 min

Rabbit Red Blood Cell

Purity: Not Reported	Haemolysis occurred at concentrations >= 5
mg/litre.



  TC \l3 "9.1.2	Subchronic, Chronic and Other Toxicity Tables 

9.2	Summary of Toxicological Dose and Endpoints for Linear Alkylbenzene
Sulfonates

Table 3. Summary of Toxicological Dose and Endpoints for Alkylbenzene
Sulfonates

Exposure

Scenario	Dose Used in Risk Assessment, UF 	Special FQPA SF*, endpoint
and Level of Concern for Risk Assessment	Study and Toxicological Effects

Acute Dietary

(All populations)	No endpoint was selected.  No effects are attributable
to a single dose.

Chronic Dietary

(All populations)	Systemic/

Reproductive NOAEL= 50  mg/kg/day

UF = 100 

Chronic RfD = 

 0.5 mg/kg/day

	FQPA SF = 1X

cPAD = 

chronic RfD

 FQPA SF

= 0.5 mg/kg/day	Systemic/Reproductive 

NOAEL= 50 mg/kg/day; 

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 

NOAEL = 85 mg/kg/day; 

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 

NOAEL= 40 mg/kg/day (0.07%)

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 

NOAEL= 50 mg/kg/day;  

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 

NOAEL = 85 mg/kg/day; 

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 

NOAEL= 40 mg/kg/day (0.07%)

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-, intermediate- and 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

NOTE:  No Special FQPA Safety Factor recommended because it is assumed
that the exposure databases (dietary food, drinking water, and
residential) are complete and that the risk assessment for each
potential exposure scenario includes all metabolites and/or degradates
of concern and does not underestimate the potential risk for infants and
children.

(a) Equation used to convert inhalation air concentration to a dose=
mg/L* absorption*respiratory volume (L/hr)*duration (hrs) * activity
factor / body weight.  Thus, 0.001 mg/L * 1*67.94 L/hr (based on default
respiratory volumes for a New Zealand Rabbit which is used as a
surrogate for a cynomolgus monkey) * 6 hrs * 1 / 2.98 kg
(b摯⁹敷杩瑨映牯丠睥娠慥慬摮删扡楢⁴獵摥愠⁳⁡畳
牲杯瑡⁥潦⁲祣潮潭杬獵洠湯敫ⱹ猠畴祤爠灥牯獴洠湯
敫⁹潢祤眠楥桧⁴慲杮獥映潲⁭⸱‶潴㌠㜮欠⥧മ̍഍
ഄ̍഍ഄ഍഍ግ䅐䕇†㈔ᔲ漠⁦㈴഍ግ䅐䕇†㈔ᔳ漠⁦
㈴഍ግ䅐䕇†㈔ᔴ漠⁦㈴഍഍഍ግ䅐䕇†㈔ᔴ഍ግ䅐䕇
†㈔ᔴ

漠⁦ㄴ഍഍

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