![](media/image1.png){width="1.1in" height="1.0638888888888889in"}Number
range CHAPTER

**UNITED STATES ENVIRONMENTAL PROTECTION AGENCY**

WASHINGTON, D.C. 20460

OFFICE OF

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

TXR No.

Date: March 23, 2006

[MEMORANDUM]{.underline}

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

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

And

William Dykstra, PhD., Toxicologist

Health Effects Division (HED) (7509C)

THRU: Alberto Protzel, Ph.D.

Senior Branch Scientist, Tox Branch

Health Effects Division (HED) (7509 C)

TO: Deborah Smegal, MPH, Toxicologist/Risk Assessor

Health Effects Division (HED) (7509 C)

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

+-----------------------------------------------------------------------+
| Number range CHAPTER                                                  |
|                                                                       |
| **SODIUM DODECYLBENZENE SULFONATE**                                   |
|                                                                       |
| **DODECYL BENZENESULFONIC ACID**                                      |
|                                                                       |
| **BENZENE SULFONIC ACIDS, C~10-16~ 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**

**1.0 HAZARD CHARACTERIZATION 4**

**2.0 REQUIREMENTS [7](#__RefHeading___Toc130724036)**

**3.0 DATA GAP(S) [8](#__RefHeading___Toc130724037)**

**4.0 HAZARD ASSESSMENT [8](#__RefHeading___Toc130724038)**

**4.1 Acute Toxicity [8](#__RefHeading___Toc130724039)**

**4.2 Subchronic Toxicity [8](#__RefHeading___Toc130724040)**

**4.3 Prenatal Developmental Toxicity
[11](#__RefHeading___Toc130724041)**

**4.4 Reproductive Toxicity 13**

**4.5 Chronic Toxicity 14**

**4.6 Carcinogenicity 15**

**4.7 Mutagenicity 17**

**4.8 Neurotoxicity 17**

**4.9 Metabolism [18](#__RefHeading___Toc130724047)**

**5.0 TOXICITY ENDPOINT SELECTION 19**

**5.2 Dermal Absorption 19**

**5.3 Classification of Carcinogenic
Potential...................................................20**

**6.0 FQPA
CONSIDERATIONS..................................................................\...20**

**6.1 Special Sensitivity to Infants and Children
[21](#__RefHeading___Toc130724051)**

**6.2 Recommendation for a Developmental Neurotoxicity Study
[21](#__RefHeading___Toc130724052)**

**8.0 REFERENCES [21](#__RefHeading___Toc130724054)**

**9.0 APPENDICES [24](#__RefHeading___Toc130724055)**

**9.1 Toxicity Profile Summary Tables
[25](#__RefHeading___Toc130724056)**

**9.1.1 Acute Toxicity Table [25](#__RefHeading___Toc130724057)**

**9.1.2 Subchronic, Chronic and Other Toxicity Tables 25**

1.  **HAZARD CHARACTERIZATION**

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

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

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

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

ingestion, or indirectly from drinking water.

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

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

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

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

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

-   Short-, intermediate-, and long-term inhalation exposure scenarios
    -- a NOAEL of 1 mg/m^3^ 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
(LD~50~s of 404 -- 1980 mg/kg), with a narrower range in mice (LD~50~s
of 1259-2300 mg/kg). This spans the acute oral toxicity categories of
III-IV. LAS are classified as acute toxicity category II for the dermal
route and category IV (least toxic) via the inhalation route.

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

*Repeated Dose Toxicity (Subchronic and Chronic)*

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

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

*Developmental Toxicity*

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

*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.

**2.0 REQUIREMENTS**[]{#__RefHeading___Toc130724036 .anchor}

> **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            | yes         | yes         |
|                                         |             |             |
| 870.1200 Acute Dermal Toxicity          | yes         | yes         |
|                                         |             |             |
| 870.1300 Acute Inhalation Toxicity      | yes         | yes         |
|                                         |             |             |
| 870.2400 Primary Eye Irritation         | yes         | yes         |
|                                         |             |             |
| 870.2500 Primary Dermal Irritation      | yes         | yes         |
|                                         |             |             |
| 870.2600 Dermal Sensitization           | yes         | yes         |
+-----------------------------------------+-------------+-------------+
| 870.3100 Oral Subchronic (rodent)       | yes         | yes         |
|                                         |             |             |
| 870.3150 Oral Subchronic (nonrodent)    | no          | yes         |
|                                         |             |             |
| 870.3200 28-Day Dermal                  | no          | yes         |
|                                         |             |             |
| 870.3250 90-Day Dermal                  | no          | \--         |
|                                         |             |             |
| 870.3465 90-Day Inhalation              | no          | yes         |
+-----------------------------------------+-------------+-------------+
| 870.3700a Developmental Toxicity        | Yes         | yes         |
| (rodent)                                |             |             |
|                                         | no          | yes         |
| 870.3700b Developmental Toxicity        |             |             |
| (nonrodent)                             | no          | yes         |
|                                         |             |             |
| 870.3800 Reproduction                   |             |             |
+-----------------------------------------+-------------+-------------+
| 870.4100a Chronic Toxicity (rodent)     | No          | yes         |
|                                         |             |             |
| 870.4100b Chronic Toxicity (nonrodent)  | no          | \--         |
|                                         |             |             |
| 870.4200a Oncogenicity (rat)            | no          | yes         |
|                                         |             |             |
| 870.4200b Oncogenicity (mouse)          | no          | \--         |
|                                         |             |             |
| 870.4300 Chronic/Oncogenicity           | no          | \--         |
+-----------------------------------------+-------------+-------------+
| 870.5100 Mutagenicity---Gene Mutation - | Yes         | yes         |
| bacterial                               |             |             |
|                                         | Yes         | yes         |
| 870.5300 Mutagenicity---Gene Mutation - |             |             |
| mammalian                               | Yes         | yes         |
|                                         |             |             |
| 870.5375 Mutagenicity---Structural      | No          | \--         |
| Chromosomal Aberrations                 |             |             |
|                                         |             |             |
| 870.5xxx Mutagenicity---Other Genotoxic |             |             |
| Effects                                 |             |             |
+-----------------------------------------+-------------+-------------+
| 870.6100a Acute Delayed Neurotox. (hen) | No          | \-          |
|                                         |             |             |
| 870.6100b 90-Day Neurotoxicity (hen)    | no          | \-          |
|                                         |             |             |
| 870.6200a Acute Neurotox. Screening     | no          | \-          |
| Battery (rat)                           |             |             |
|                                         | no          | \-          |
| 870.6200b 90 Day Neuro. Screening       |             |             |
| Battery (rat)                           | no          | \-          |
|                                         |             |             |
| 870.6300 Develop. Neuro                 | no          | \-          |
+-----------------------------------------+-------------+-------------+
| 870.7485 General Metabolism             | No          | Yes         |
|                                         |             |             |
| 870.7600 Dermal Penetration             | No          | \-          |
+-----------------------------------------+-------------+-------------+
| Special Studies for Ocular Effects      | No          | \-          |
|                                         |             |             |
| Acute Oral (rat)                        | no          | \-          |
|                                         |             |             |
| Subchronic Oral (rat)                   | no          | \-          |
|                                         |             |             |
| Six-month Oral (dog)                    | no          | \-          |
+-----------------------------------------+-------------+-------------+

**3.0 DATA GAP(S)**[]{#__RefHeading___Toc130724037 .anchor}

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

**4.0 HAZARD ASSESSMENT**[]{#__RefHeading___Toc130724038 .anchor}

**4.1 Acute Toxicity**[]{#__RefHeading___Toc130724039 .anchor}

[Adequacy of data base for acute toxicity]{.underline}: 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 | MRID No.        | Results           | To     |
| Type                 |                 |                   | xicity |
|                      |                 |                   | Ca     |
|                      |                 |                   | tegory |
+----------------------+-----------------+-------------------+--------+
| 870.1100 Acute oral  | Multiple        | LD~50~ = range    | III-IV |
| toxicity             |                 | from 404 to over  |        |
|                      |                 | 5000 mg/kg        |        |
+----------------------+-----------------+-------------------+--------+
| 870.1200 Acute       | 94032006        | LD~50~ = 1200     | II     |
| dermal toxicity      |                 | mg/kg             |        |
+----------------------+-----------------+-------------------+--------+
| 870.1300 Acute       | 003442\*        | LC~50~ = 200 mg/L | IV     |
| inhalation toxicity  |                 |                   |        |
+----------------------+-----------------+-------------------+--------+
| 870.2400 Acute eye   | 0033443\*       | Corneal opacity   | I      |
| irritation           |                 | not reversed at   |        |
|                      |                 | 72 hours.         |        |
+----------------------+-----------------+-------------------+--------+
| 870.2500 Acute       | 003444\*        | Severe irritation | II     |
| dermal irritation    |                 | at 72 hours       |        |
+----------------------+-----------------+-------------------+--------+
| 870.2600 Skin        | Open Literature | Weak to moderate  |        |
| sensitization        |                 | sensitization     |        |
|                      | { Nusair TL, PJ |                   |        |
|                      | Danneman, J     |                   |        |
|                      | Stotte, PHS Bay |                   |        |
|                      | (1988) Consumer |                   |        |
|                      | Products: Risk  |                   |        |
|                      | Assessment      |                   |        |
|                      | Process for     |                   |        |
|                      | Contact         |                   |        |
|                      | Sensitization,  |                   |        |
|                      | Toxicologist    |                   |        |
|                      | 8:258. (HERA)}  |                   |        |
+----------------------+-----------------+-------------------+--------+

\* Tox record No.

**4.2 Subchronic Toxicity**[]{#__RefHeading___Toc130724040 .anchor}

[Adequacy of data base for subchronic toxicity]{.underline}: 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.

3100. **90-Day Oral Toxicity -- Rat**

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

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

3465. **90-Day Inhalation -- Rat**

This study is not available in the database of this chemical; however,
there is an acceptable 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/m^3^) - 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% C~12~ 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/m^3^ detergent dust combined with up to 0.1 mg/m^3^
enzyme dust. The detergent dust at 100 mg/m^3^ 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 noticed that most uses of this
detergent are in liquid form. It is a common misconception that the
small particle size used in an animal study (MMAD of 1-3 um in acute
studies, 1-4 um in multiple exposure studies) has no relevance to the
large particle size that comes from medium to coarse powdered material
or a liquid-powder mix during use. Detergents are typically mixed with
large quantities of water before use. When the aqueous mix is used,
droplets rapidly shrink as they fall due to water evaporation. The
degree of shrinkage depends on temperature, relative humidity, particle
size, and the length of time that the droplets are suspended in the air.
Since humans are capable of inhaling particles \>100 um, it is
reasonable to expect a significant portion of these particles to be
inhaled. While most large particles are captured in the nose, some are
capable of reaching the lungs. Large particles have the potential to do
considerable local damage if they are respirable because of the volume
of material they contain.

[Core Classification]{.underline}: ACCEPTABLE

**4.3 Prenatal Developmental Toxicity**[]{#__RefHeading___Toc130724041
.anchor}

[Adequacy of data base for Prenatal Developmental Toxicity]{.underline}:
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]{.underline} [libitum.]{.underline} 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]{.underline}: 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]{.underline} [libitum]{.underline}. 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 37^o^C 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]{.underline}: ACCEPTABLE

**870.3700b Prenatal Developmental Toxicity Study -- Rabbit**

This study is included with section 870.3700a.

**4.4 Reproductive Toxicity**

[Adequacy of data base for Reproductive Toxicity]{.underline}: 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 P~0~ 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 (F~1a~), and examined, culled to
8/litter on day 4, and sacrificed at day 21 of lactation. Pups of the
F~1a~ and F~2a~ litters were both sacrificed after day 21 of lactation.
Ten days later, the rats were again mated to produce the F~1b~ litters.
20/sex/dose of F~1b~ weanlings were selected to generate the P~1~ and
P~2~ parental animals for generating the F~2a~, F~2b,~ F~3a~ and F~3b~
litters.

Food consumption, body weight, and food efficiency were recorded weekly
for the first 8 weeks. Five male and 5 female rats from the F~1b~ and
F~2b~ parental groups and F~3b~ 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% F~2b~ 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 F~2b~ 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]{.underline}: ACCEPTABLE

**4.5 Chronic Toxicity**

[Adequacy of data base for chronic toxicity]{.underline}: 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**

[Adequacy of data base for Carcinogenicity]{.underline}: 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]{.underline}: Mortality was 59% in Group I, 31% in Group II
and 23% in Group III.

[Tumors]{.underline}:

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]{.underline}: 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 LD~50~ dose for SDDBS.

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

**870.4200b Carcinogenicity (feeding) - Mouse**

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

**4.7 Mutagenicity**

[Adequacy of data base for Mutagenicity]{.underline}: The data base for
Mutagenicity is considered adequate based.

**Gene Mutation**

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

#  Cytogenetics

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

**Other Genotoxicity**

+-----------------------+----------------------------------------------+
| Guideline \# 870.5300 | LAS tested negative in Syrian Hamster Ovary  |
|                       | (SHE) cells at up to 50 micrograms/plate.    |
| study type:           |                                              |
| [In]{.underline}      |                                              |
| [Vitro]{.underline}   |                                              |
| cell transformation   |                                              |
|                       |                                              |
| MRID No. 43498429     |                                              |
|                       |                                              |
| Classification,:      |                                              |
| Literature,           |                                              |
| acceptable            |                                              |
+-----------------------+----------------------------------------------+

**4.8 Neurotoxicity**

[Adequacy of data base for Neurotoxicity]{.underline}: 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.

9.  **Metabolism**

[]{#__RefHeading___Toc130724047 .anchor}

[Adequacy of data base for metabolism:]{.underline} 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.

7485. **Metabolism -- Rat**

In a rat metabolism study (MRID 43498431), groups of Charles- River CD
male-rats, 150-200g BW, were used in the study. LAS-S^35^ 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
S^35^ was not in inorganic form and no intact LAS-S^35^ was detected.
Following methylation, one urinary metabolite was identified as 4-(4'-
methylsulfophenyl) pentanoate. LAS-S^35^ 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-S^35^ 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---S^35^ excretion by studies in rats with cannulated bile ducts
given 1.2 mg/kg of LAS-S^35^ orally. The percent of radioactivity in
bile was similar to that in feces and most label was in the urine.

[Core Classification]{.underline}: 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 C^14^(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
C^14^ 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 C^14^ 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 C^14^ 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]{.underline}: 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.

10. **Special/Other Studies: N/A**

**5.0 TOXICITY ENDPOINT SELECTION**

1.  **See Section 9.2 for Endpoint Selection Table.**

**5.2 Dermal Absorption:**

Quantification of dermal risk is not required since: 1) the alkylbenzene
sulfonates are surfactants that are dermal irritants at concentrations
generally greater than 20% solution. Thus, dermal 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).

3.  **Classification of Carcinogenic Potential:**

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

**6.0 FQPA CONSIDERATIONS**

1.  **Special Sensitivity to Infants and Children**

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

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

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

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

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

> []{#__RefHeading___Toc130724051 .anchor}

**6.2 Recommendation for a Developmental Neurotoxicity
Study**[]{#__RefHeading___Toc130724052 .anchor}

A DNT is not required because there is no evidence of either
neurotoxicity or susceptibility to the young following LAS exposure to
laboratory animals.

**7.0 OTHER ISSUES: N/A**

**8.0 REFERENCES**[]{#__RefHeading___Toc130724054 .anchor} in MRID order

+----------------+-----------------------------+-----------------------+
| **MRID No.**   | **Guideline No./Study       | **Source**            |
|                | Type**                      |                       |
+================+=============================+=======================+
| Multiple       | 870.1100 Acute oral         | Tox Oneliner          |
| studies        | toxicity                    |                       |
+----------------+-----------------------------+-----------------------+
| 94032006       | 870.1200 Acute dermal       | Tox Oneliner          |
|                | toxicity                    |                       |
+----------------+-----------------------------+-----------------------+
| 003442\*       | 870.1300 Acute inhalation   | Tox Oneliner          |
|                | toxicity                    |                       |
+----------------+-----------------------------+-----------------------+
| 0033443\*      | 870.2400 Acute eye          | Tox Oneliner          |
|                | irritation                  |                       |
+----------------+-----------------------------+-----------------------+
| 003444\*       | 870.2500 Acute dermal       | Tox Oneliner          |
|                | irritation                  |                       |
+----------------+-----------------------------+-----------------------+
| N/A            | 870.2600 Skin sensitization | Open Literature       |
+----------------+-----------------------------+-----------------------+
| N/A            | 870-3100 Subchronic Oral    | Ikawa et al.1978.     |
|                | Toxicity -- Rat             | HERA-2004)            |
+----------------+-----------------------------+-----------------------+
| N/A            | 870-3100 Subchronic Oral    | Ito, et al. (1978) J. |
|                | Toxicity -- Rat             | Med. Soc. Toho Univ.  |
|                |                             | 25: 850-875.          |
+----------------+-----------------------------+-----------------------+
| 43498413       | Subchronic Oral Toxicity -- | HERA-2004             |
|                | Monkey                      |                       |
+----------------+-----------------------------+-----------------------+
| N/A            | 21/28-Day Dermal Toxicity   | Mathur et al. (1992). |
|                | -- Guinea Pig               | J Toxicol Cutan       |
|                |                             | Ocular Toxicol,       |
|                |                             | 11(1): 3-13. (WHO     |
|                |                             | 169).                 |
+----------------+-----------------------------+-----------------------+
| 43498403       | Subchronic Inhalation       | HERA-2004             |
|                | Toxicity -- Monkey          |                       |
+----------------+-----------------------------+-----------------------+
| 43498426       | 870.3700a Prenatal          | Palmer et al. Part I, |
|                | Developmental Toxicity      | HERA-204              |
|                | Study -- Rat, Mouse,        |                       |
|                | Rabbit,                     |                       |
+----------------+-----------------------------+-----------------------+
| 43511403       | Dermal Developmental        | Palmer et al. Part    |
|                | Toxicity --- Rat, Rabbit,   | III, HERA-2004        |
|                | Mouse                       |                       |
+----------------+-----------------------------+-----------------------+
| 43498424 &     | Mouse-Developmental         |                       |
| 43498425       |                             |                       |
+----------------+-----------------------------+-----------------------+
| 43498416       | 870.3800 Reproduction and   |                       |
|                | Fertility Effects -- Rat    |                       |
+----------------+-----------------------------+-----------------------+
|                | 870.4100a Chronic Toxicity  | Yoneyama et al.,1976  |
|                | -- Rat                      |                       |
|                |                             | (see tox profile      |
|                |                             | table)                |
+----------------+-----------------------------+-----------------------+
|                | 870.4100b Chronic Toxicity  | Yoneyama et al.,1976  |
|                | -- Mouse                    |                       |
|                |                             | (see tox profile      |
|                |                             | table)                |
+----------------+-----------------------------+-----------------------+
| 43498420 &     | 870.4200a Carcinogenicity   |                       |
| 43498419       | Study -- rat                |                       |
+----------------+-----------------------------+-----------------------+
| 43498416       | 870.4200a Carcinogenicity   |                       |
|                | Study -- rat                |                       |
+----------------+-----------------------------+-----------------------+
| 43498429       | 870.5100 Gene Mutation -    |                       |
|                | bacterial                   |                       |
+----------------+-----------------------------+-----------------------+
| 43498428       | 870.5385 Structural         |                       |
|                | Chromosomal Aberrations     |                       |
+----------------+-----------------------------+-----------------------+
| 43498427       | 870.5300 [In]{.underline}   |                       |
|                | [Vitro]{.underline} cell    |                       |
|                | transformation              |                       |
+----------------+-----------------------------+-----------------------+
| **MRID No.**   | **Guideline No./Study       | **Source**            |
|                | Type**                      |                       |
+----------------+-----------------------------+-----------------------+
| 43498431       | 7485. Metabolism -- Rat     |                       |
+----------------+-----------------------------+-----------------------+
| 43498410       | Metabolism -- Monkey        |                       |
+----------------+-----------------------------+-----------------------+
|                | Isolated human skin         | Howes,1975            |
|                | preparations                |                       |
|                |                             | (see tox profile      |
|                |                             | table)                |
+----------------+-----------------------------+-----------------------+

\* Tox record No.

**[Other Sources]{.underline}:**

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

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

9.0APPENDICES[]{#__RefHeading___Toc130724055 .anchor}

Tables for Use in Risk Assessment

1.  Toxicity Profile Summary Tables

[]{#__RefHeading___Toc130724056 .anchor}

9.1.1 Acute Toxicity Table[]{#__RefHeading___Toc130724057 .anchor} - See
Section 4.1

2.  Subchronic, Chronic and Other Toxicity Tables:

+-----------+-------------+--------------+----------------------------+
| **        | **MRID      | **Dosing and | **Results**                |
| Guideline | No./**      | Animal       |                            |
| No./**    |             | I            |                            |
|           | **Reference | nformation** |                            |
| **Study   | Inf         |              |                            |
| Type**    | ormation/** |              |                            |
|           |             |              |                            |
|           | **Study     |              |                            |
|           | Class       |              |                            |
|           | ification** |              |                            |
+===========+=============+==============+============================+
| **S       |             |              |                            |
| ubchronic |             |              |                            |
| T         |             |              |                            |
| oxicity** |             |              |                            |
+-----------+-------------+--------------+----------------------------+
| 870.3100  | Bornmann et | 0.01% of a   | No detrimental effects on  |
|           | al (1963)   | preparation  | body weight and no         |
| Oral      | Study of a  | containing   | pathological effects,      |
| S         | Detergent   | 51% LAS was  | including tumors, were     |
| ubchronic | Based on    | administered | reported                   |
| (rodent)  | Dod         | in the       |                            |
|           | ecylbenzene | drinking     |                            |
|           | Sulfonate.  | water for    |                            |
|           | Fette       | 100 weeks    |                            |
|           | Seifen      |              |                            |
|           | Anstrichm,  | Rats         |                            |
|           | 65 (10):    | (60/sex)     |                            |
|           | 818-824.    |              |                            |
|           | (EHC 169)   | Purity: Not  |                            |
|           |             | Reported     |                            |
|           | **Open      |              |                            |
|           | L           |              |                            |
|           | iterature** |              |                            |
+-----------+-------------+--------------+----------------------------+
| 870.3100  | Ikawa et    | LAS was      | LAS suppressed body weight |
|           | al.,        | administered | gain and the relative      |
| Oral      | (1980)/     | for 2, 4, or | liver weight was increased |
| S         |             | 12 weeks at  | after two weeks. Serum     |
| ubchronic | Ann. Rep.   | a single     | biochemical alterations    |
|           | Tokyo       | dose of 1.5% | included: significant      |
| (rodent)  | Metrop.     | in the diet  | increases in ALP, GTP (at  |
|           | Res. Lab.   | (750         | 2, 4, 12 weeks);           |
|           | Public      | mg/kg/d).    | significant decreases in   |
|           | Health.     |              | cholesterol and protein (4 |
|           | 29(2):      | Male rats    | weeks); decreases in liver |
|           | 51-54(Z).   | (five/group) | enzymes G6Pase and G6PDH   |
|           | 1978 (in    |              | and increases in           |
|           | Japanese,   | Purity not   | isocitrate DH (all at 2,   |
|           | see WHO,    | reported.    | 4, 12 weeks). The          |
|           | 1996 and    |              | following enzymes          |
|           | HERA,       |              | associated with kidney     |
|           | 2004).      |              | function were also         |
|           |             |              | altered: decreases in      |
|           | **Open      |              | G6Pase, 5'nucleotidase (at |
|           | L           |              | 2, 4, 12 weeks) and        |
|           | iterature** |              | Na,K-ATPase (12 wks);      |
|           |             |              | increase in LDH (12 wks)   |
|           |             |              | and IDH (2,4 wks).         |
+-----------+-------------+--------------+----------------------------+
| 870.3100  | Ito, et al. | Ad           | LAS-Na: Body weight        |
|           | (1978)      | ministration | increase was suppressed;   |
| Oral      | Acute,      | by oral      | feed-efficacy was          |
| S         | Subacute,   | gavage at    | decreased, and liver       |
| ubchronic | and Chronic | doses of 0,  | weight increased at 500    |
| (rodent)  | Toxicity of | 155, 310, or | mg/kg/day. NOAEL: 125      |
|           | Magnesium   | 620          | mg/kg bw/d.                |
|           | LAS         | mg/kg/day    |                            |
|           | (LAS-Mg).   | (LAS-Mg) and |                            |
|           | J. Med.     | 125, 250,    |                            |
|           | Soc. Toho   | and 500      |                            |
|           | Univ. 25:   | mg/kg/day    |                            |
|           | 850-875.    | (LAS-Na) for |                            |
|           |             | one month    |                            |
|           | **Open      |              |                            |
|           | L           | Sp           |                            |
|           | iterature** | rague-Dawley |                            |
|           |             | Rats         |                            |
|           |             | (1           |                            |
|           |             | 2/sex/group) |                            |
|           |             |              |                            |
|           |             | Purity:      |                            |
|           |             | 99.5%        |                            |
+-----------+-------------+--------------+----------------------------+
| 870.3100  | **MRID No.  | SDDBS        | NOEL: 5000 ppm (HDT)       |
|           | 43498412**  | administered |                            |
| Oral      | Kay et al.  | in the diet  | Two low dose males died    |
| S         | (1965)      | at dietary   | early in the study from    |
| ubchronic | Subacute    | levels of 0, | respiratory illness There  |
| (rodent)  | Oral        | 200, 1000,   | was no compound-related    |
|           | Toxicity of | and 5000 ppm | effects in body weight,    |
|           | a           | for 90 days  | food consumption,          |
|           | Bio         |              | hematology, urine          |
|           | degradable, | Weanling     | analysis, organ weight,    |
|           | Linear      | Sp           | and histopathology.        |
|           | A           | rague-Dawley |                            |
|           | lkylbenzene | Rat          |                            |
|           | Sulfonate.  | (            |                            |
|           | Toxicol     | 10/sex/dose) |                            |
|           | Appl.       |              |                            |
|           | Pharmacol.  | Purity:      |                            |
|           | 7: 812-818  | 87.9% a.i.   |                            |
|           | (HERA)      |              |                            |
|           |             |              |                            |
|           | **A         |              |                            |
|           | cceptable** |              |                            |
|           |             |              |                            |
|           | Guideline   |              |                            |
+-----------+-------------+--------------+----------------------------+
| 870.3100  | # MR        | LAS was      | NOEL: \< 50 mg/kg/d        |
|           | ID No. 4351 | administered |                            |
| Oral      | 1401 Mathur | as a         | LOEL: 50 mg/kg/d based on  |
| S         |  et al. (19 | commercial   | alterations of several     |
| ubchronic | 86) Toxicol | synthetic    | enzymes indicative of      |
| (rodent)  | ogical Eval | detergent    | liver and kidney damage    |
|           | uation of a | solution at  |                            |
|           |  Synthetic  | doses of 0,  |                            |
|           | Detergent a | 50, 100, or  |                            |
|           | fter Repeat | 250          |                            |
|           | ed Oral Ing | mg/kg/day in |                            |
|           | estion in R | the feed for |                            |
|           | ats. Indust | 10 weeks     |                            |
|           | rial Toxico |              |                            |
|           | logy Resear | F Albino Rat |                            |
|           | ch Centre,  | (9/group)    |                            |
|           | Mahatma Gan |              |                            |
|           | ghi Marg, L | Purity: Not  |                            |
|           | ucknow Stud | Reported     |                            |
|           | y No. DDBSA |              |                            |
|           |  JV-RP-013. |              |                            |
|           |             |              |                            |
|           | Acceptable  |              |                            |
+-----------+-------------+--------------+----------------------------+
| 870.3100  | # MRID No.  | LAS and ABS  | NOEL: 50 mg/kg/d           |
|           | 43498402 Os | were         |                            |
| Oral      | er et al. ( | administered | LEL: 250 mg/kg/d for       |
| S         | 1965) Toxic | at dietary   | increased absolute and     |
| ubchronic | ologic Stud | levels of 0, |                            |
| (rodent)  | ies with Br | 50, or 250   | relative liver weight in   |
|           | anched and  | mg/kg/day,   | both sexes (21%) and       |
|           | Linear Alky | adjusted for | increased relative cecal   |
|           | l Benzene S | bw and fc,   | weight (21%) in males      |
|           | ulfonates i | for 90 days  |                            |
|           | n the Rat.  |              |                            |
|           | Toxicol. Ap | FDRL Strain  |                            |
|           | pl. Pharmac | (Wis         |                            |
|           | ol. 7: 819- | tar-derived) |                            |
|           | 825. (HERA) | Rat          |                            |
|           |             | (            |                            |
|           | #           | 15/sex/dose) |                            |
|           |  Acceptable |              |                            |
|           |             | Purity: Not  |                            |
|           | Guideline   | Reported     |                            |
+-----------+-------------+--------------+----------------------------+
| 870.3100  | Watari et   | Ben          | Liver effects were         |
|           | al. (1977)  | zenesulfonic | observed at the only dose  |
| Oral      | Ultr        | acid,        | tested (17-20 mg/kg/d),    |
| S         | astructural | C10-13-      | but they disappeared       |
| ubchronic | O           | alkyl        | following the 2-month      |
| (rodent)  | bservations | derivatives, | recovery period.           |
|           | of the      | sodium salt  |                            |
|           | Protective  | was          |                            |
|           | Effect of   | administered |                            |
|           | G           | in the       |                            |
|           | lycyrrhizin | drinking     |                            |
|           | for Mouse   | water for 6  |                            |
|           | Liver       | months at 0  |                            |
|           | Injury      | and 100 ppm  |                            |
|           | Caused by   | with 2       |                            |
|           | Oral        | months       |                            |
|           | Adm         | recovery (M: |                            |
|           | inistration | 0 and 17     |                            |
|           | of          | mg/kg bw, F: |                            |
|           | Detergent   | 0 and 20     |                            |
|           | Ingredients | mg/kg bw)    |                            |
|           | (LAS), J.   |              |                            |
|           | Clin.       | M/F ddy      |                            |
|           | Electron.   | Mouse        |                            |
|           | Microscopy  |              |                            |
|           | (Nihon      | Purity: Not  |                            |
|           | Rinsho      | Reported     |                            |
|           | Den         |              |                            |
|           | shikenbikyo |              |                            |
|           | Kaishi) 10  |              |                            |
|           | (1-2):      |              |                            |
|           | 121-139.    |              |                            |
|           |             |              |                            |
|           | **Open      |              |                            |
|           | L           |              |                            |
|           | iterature** |              |                            |
+-----------+-------------+--------------+----------------------------+
| 870.3100  | Yoneyama &  | LAS was      | Body weight gain was       |
|           | Hiraga      | administered | suppressed in the group    |
| Oral      | (1977)      | in the diet  | receiving 540 mg/kg bw/d   |
| S         | Effect of   | at           | at four weeks, and the     |
| ubchronic | Linear      | co           | relative liver weight was  |
| (rodent)  | A           | ncentrations | increased at two weeks and |
|           | lkylbenzene | of 180, 360, | thereafter in the groups   |
|           | Sulfonate   | or 540 mg/kg | receiving 360 mg/kg bw/d   |
|           | on Serum    | bw/d for two | and 540 mg/kg bw/d. The    |
|           | Lipid in    | and four     | levels of triglyceride and |
|           | Rats, J Ann | weeks        | total lipids in the serum  |
|           | Rep Tokyo   |              | had decreased markedly at  |
|           | Metrop Res  | M Wistar Rat | two weeks in all the       |
|           | Lab, Public | (5/group)    | experimental groups, and   |
|           | Health      |              | the levels of              |
|           | 28(2):      | Purity: 60%  | phospholipids and          |
|           | 109-111.    | a.i.         | cholesterol in the serum   |
|           | (HERA)      |              | had decreased              |
|           |             |              | significantly at two weeks |
|           | **Open      |              | in the groups given 360    |
|           | L           |              | and 540 mg/kg bw/d. These  |
|           | iterature** |              | 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  | Yoneyama et | LAS was      | Uptake of acetate-1-14C by |
|           | al. (1978)  | administered | lipids in the liver was    |
| Oral      | Effects of  | at a         | increased in both groups;  |
| S         | LAS on      | c            | uptake of phospholipids    |
| ubchronic | In          | oncentration | and triglycerides tended   |
| (rodent)  | corporation | of 200 mg/kg | to increase, and that of   |
|           | of          | bw/d in the  | phospholipids increased    |
|           | Ac          | diet or in   | significantly in rats      |
|           | etate-1-14C | drinking     | given LAS in the diet.     |
|           | in Liver    | water (560   |                            |
|           | Lipids in   | mg/kg bw/d)  |                            |
|           | Rats. J Ann | for two      |                            |
|           | Rep Tokyo   | weeks to     |                            |
|           | Metrop Res  | determine    |                            |
|           | Lab Public  | the effect   |                            |
|           | Health, 29  | on the       |                            |
|           | (2): 55-57. | synthesis of |                            |
|           |             | lipids in    |                            |
|           | **Open      | the liver    |                            |
|           | L           |              |                            |
|           | iterature** | M Wistar Rat |                            |
|           |             | (5/group)    |                            |
|           |             |              |                            |
|           |             | Purity: Not  |                            |
|           |             | Reported     |                            |
+-----------+-------------+--------------+----------------------------+
| 870.3100  | #           | LAS was      | At 300 (po) and 1.0 (sc)   |
|           | MRID No. 43 | given to     | mg/kg bw/day, the monkeys  |
| Oral      | 498413 Heyw | four groups  |                            |
| S         | ood et al.  | of three     | vomited frequently and     |
| ubchronic | (1978) Toxi | males and    | usually within 3 hours of  |
| (rodent)  | cology Stud | three        | administration. An         |
|           | ies of Line | females at   | increased frequency of     |
|           | ar Alkyl Su | doses of 30, | loose or liquid faeces was |
|           | lfonate (LA | 150, 300     | recorded for animals       |
|           | S) in Rhesu | mg/kg bw/day | receiving 150 (po) and 0.5 |
|           | s Monkeys I | per gavage   | (sc) mg/kg bw/day. These   |
|           | . Simultane | (po) and     | effects                    |
|           | ous Oral an | si           |                            |
|           | d Subcutane | multaneously | are probably related to    |
|           | ous Adminis | with 0.1,    | the inherent irritative    |
|           | tration for | 0.5, or 1.0  | effects of LAS rather than |
|           |  28 Days. T | mg/kg bw/day | to its systemic toxicity.  |
|           | oxicol. App |              |                            |
|           | l. Pharmaco | su           | Fibrosis of the injection  |
|           | l. 11: 245- | bcutaneously | sites was found among the  |
|           | 250. (HERA) | (sc).        | entire test group, the     |
|           |             | Control      | incidence and severity     |
|           | Acceptable  | groups were  | being                      |
|           |             | used.        |                            |
|           | Guideline   |              | dose related.              |
|           |             | Rhesus       | Ophthalmoscopy, laboratory |
|           |             | Monkey       | examination of blood and   |
|           |             | (            | urine, organ weight        |
|           |             | 3/sex/dose), | analysis and               |
|           |             | 18-36 months |                            |
|           |             | old          | histopathological          |
|           |             |              | investigation did not      |
|           |             | Purity: Not  | detect any further         |
|           |             | Reported     | 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  | Mathur et   | A solution   | The activities of          |
|           | al. (1992)  | of LAS in    | B-glucuronidase, gamma-    |
| 21-Day    | Effect of   | distilled    | glutamyl transpeptidase,   |
| Dermal    | Dermal      | water        | 5-nucleotidase, and        |
|           | Exposure to | equivalent   | sorbitol dehydrogenase     |
|           | LAS         | to 60 mg/kg  | were increased in liver    |
|           | Detergent   | bw was       | and kidney. Lipid          |
|           | and HCH     | applied to a | peroxidation was increased |
|           | Pesticide   | 4-cm2 area   | in the kidney but not in   |
|           | in Guinea   | of clipped   | liver, and the glutathione |
|           | Pigs:       | dorsal skin  | content was unchanged in   |
|           | Biochemical | daily for 30 | both organs. Extensive     |
|           | and         | days         | fatty changes were found   |
|           | Hist        |              | in hepatic lobules, with   |
|           | opathologic | 12 Guinea    | dilation of sinusoids;     |
|           | Changes in  | Pigs         | tubular lesions were found |
|           | Liver and   |              | in the kidney,             |
|           | Kidney. J   | Purity: Not  | predominantly in the       |
|           | Toxicol     | Reported     | proximal and distal        |
|           | Cutan       |              | portions.                  |
|           | Ocular      |              |                            |
|           | Toxicol,    |              |                            |
|           | 11(1):      |              |                            |
|           | 3-13. (WHO  |              |                            |
|           | 1996)       |              |                            |
|           |             |              |                            |
|           | **Open      |              |                            |
|           | L           |              |                            |
|           | iterature** |              |                            |
+-----------+-------------+--------------+----------------------------+
| 870.3200  | Tox Record  | SDDBS (end   | NOEL: \> 200 mg/kg/d       |
|           | No. 003441  | use product  |                            |
| 21-Day    | Subchronic  | Comet        |                            |
| Dermal    | (28-day)    | Cleanser)    |                            |
|           | P           | was applied  |                            |
|           | ercutaneous | to the skin  |                            |
|           | Toxicity    | of rabbits   |                            |
|           | (Rabbit) of | for 28 days  |                            |
|           | Compound:   | at 200       |                            |
|           | B0002.01,   | mg/kg/d. The |                            |
|           | (B          | hair of each |                            |
|           | io/dynamics | rabbit was   |                            |
|           | Inc.,       | clipped from |                            |
|           | Project No. | its trunk,   |                            |
|           | 4717-77,    | so as to     |                            |
|           | March 17,   | expose       |                            |
|           | 1978,       | a            |                            |
|           | submitted   | pproximately |                            |
|           | by Procter  | 25% of the   |                            |
|           | and Gambel  | total body   |                            |
|           | Company,    | surface area |                            |
|           | May 10,     | and the skin |                            |
|           | 1978).      | was abraded  |                            |
|           |             | daily just   |                            |
|           | **Una       | prior to     |                            |
|           | cceptable** | treatment.   |                            |
|           |             |              |                            |
|           | C           | 20 M/F       |                            |
|           | ore-Minimum | Albino New   |                            |
|           | Data        | Zealand      |                            |
|           |             | White        |                            |
|           |             | Rabbits      |                            |
|           |             | (            |                            |
|           |             | 5/sex/group) |                            |
|           |             |              |                            |
|           |             | Purity: 10%  |                            |
+-----------+-------------+--------------+----------------------------+
| 870.3465  | # MRI       | SDDBS was    | NOEL: 1 mg/m3 detergent    |
|           | D No. 43498 | administered | dust combined with         |
| 90-Day    | 403 Coate e | a SDDBS      |                            |
| I         | t al. (1978 | mixture at   | up to 0.1 mg/m3 enzyme     |
| nhalation | ) Respirato | levels of 0, | dust.                      |
|           | ry Toxicity | 100          |                            |
|           |  of Enzyme  | (detergent), | The detergent dust alone   |
|           | Detergent D | and \[ .001, | at 100 mg/m^3^ caused      |
|           | ust. Toxico | .01, 0.1 and | gross signs of respiratory |
|           | l. Appl. Ph | 1 (enzyme)\] | distress, pulmonary        |
|           | armacol., 4 | together     | histopathological effects, |
|           | 5: 477-496. | with \[+0,   | and pulmonary function     |
|           |             | 1, 10, and   | impairment indicative of   |
|           | Acceptable  | 100          | constricted bronchioles.   |
|           |             | (            | Exposure to 10 or 100      |
|           | Guideline   | detergent)\] | mg/m^3^ together with 0.01 |
|           |             | mg/m3 for 6  | and 0.1 mg/m^3^ enzyme     |
|           |             | hours daily, | dust produced the same     |
|           |             | 5 days a     | effects along with weight  |
|           |             | week, for 6  | loss and decreased weight  |
|           |             | months       | gain.                      |
|           |             |              |                            |
|           |             | 12 groups of |                            |
|           |             | 5 M/4 F      |                            |
|           |             | Cynomolgus   |                            |
|           |             | Monkeys      |                            |
|           |             |              |                            |
|           |             | Purity: 13%  |                            |
+-----------+-------------+--------------+----------------------------+
| **Deve    |             |              |                            |
| lopmental |             |              |                            |
| T         |             |              |                            |
| oxicity** |             |              |                            |
+-----------+-------------+--------------+----------------------------+
| 870.3700a | Daly et al. | LAS was      | NOAEL (maternal): 20 mg/kg |
|           | (1980) A    | applied to   | bw/d                       |
| Deve      | Teratology  | the skin on  |                            |
| lopmental | Study of    | days 0       | NOAEL (fetuses): 400 mg/kg |
| Toxicity  | Topically   | through 21   | bw/d                       |
| (rodent)  | Applied LAS | of gestation |                            |
|           | in Rats,    | at doses of  | Maternal toxicity: the     |
|           | Fd. Cosmet. | 20, 100, and | dams treated with 400      |
|           | Toxicol.    | 400 mg/kg    | mg/kg bw/day and 100 mg/kg |
|           | 18: 55-58.  | bw/d         | bw/day showed inhibition   |
|           | (HERA)      |              |                            |
|           |             | Rat          | of body weight gain and    |
|           | **Open      |              | llocal skin effects that   |
|           | L           | Purity: Not  | compromised the integrity  |
|           | iterature** | Reported     | 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 | Endo et al. | LAS was      | NOAEL (maternal): 383      |
|           | (1980)      | administered | mg/kg bw/d (rat)           |
| Deve      | Studies of  | in the       |                            |
| lopmental | the Chronic | drinking     | LOAEL (maternal): 3030     |
| Toxicity  | Toxicity    | water at     | mg/kg bw/d (rabbit)        |
| (rodent)  | and         | 0.1%,        |                            |
|           | Ter         | c            | NOAEL (fetuses): 383 mg/kg |
|           | atogenicity | orresponding | bw/d (rat)                 |
|           | of          | to 383 mg/kg |                            |
|           | Synthetic   | bw/d for     | LOAEL (fetuses): 3030      |
|           | S           | rats and up  | mg/kg bw/d (rabbit)        |
|           | urfactants, | to 3030      |                            |
|           | Ann. Rep.   | mg/kg bw/d   | The effect on the dams was |
|           | Tokyo       | for rabits   | a slight inhibition of     |
|           | Metrop.     | from day 6   | body weight gain in the    |
|           | Res. Inst.  | to 15 (rats) | rabbits. The litter        |
|           | Environ.    | and day 6 to | parameters of both species |
|           | Prot.       | 18 (rabbits) | did not show any           |
|           | (Tokyo      | of           | significant differences    |
|           | Kogai       | pregnancy.   | from those of the          |
|           | Kenkyujo    |              | controls. Delayed          |
|           | Nempo),     | F Rat and    | ossification was observed  |
|           | 236-246.    | Rabbit       | in rabbits, but there was  |
|           | (HERA)      |              | no increase in             |
|           |             | Purity: Not  | malformations in either    |
|           | **Open      | Reported     | the rabbits or the rats.   |
|           | L           |              |                            |
|           | iterature** |              |                            |
+-----------+-------------+--------------+----------------------------+
| 870.3700a | Imahori et  | LAS was      | NOAEL (maternal): 150      |
|           | al. (1976)  | applied      | mg/kg bw/d                 |
| Deve      | Effects of  | daily at     |                            |
| lopmental | LAS Applied | dermal doses | NOAEL (fetuses): 1500      |
| Toxicity  | Dermally to | of 15, 150,  | mg/kg bw/d                 |
| (rodent)  | Pregnant    | and 1500     |                            |
|           | Mice on the | mg/kg bw/d   | The 1500 mg/kg bw/day      |
|           | Pregnant    | on days 6    | group showed a clear       |
|           | Mice and    | through day  | decrease in the pregnancy  |
|           | their       | 15 of        | rate (67.9%) when          |
|           | Fetuses, J. | pregnancy    |                            |
|           | Jpn. J.     |              | compared with a rate of    |
|           | Public      | F Mouse      | 96.3% in the controls.     |
|           | Health      |              | However, there were no     |
|           | (Nihon      | Purity: Not  | decreases in the litter    |
|           | Koshueisei  | Reported     | size, and                  |
|           | Zasshi)     |              |                            |
|           | 23(2):      |              | no changes in the litter   |
|           | 68-72.      |              | parameters with the        |
|           | (HERA)      |              | exception of a slight      |
|           |             |              | decrease in foetal body    |
|           | **Open      |              | weight. There              |
|           | L           |              |                            |
|           | iterature** |              | were no significant        |
|           |             |              | increases in the incidence |
|           |             |              | of malformations in the    |
|           |             |              | foetuses.                  |
+-----------+-------------+--------------+----------------------------+
| 870.3700a | **MRID No.  | LAS was      | NOEL (maternal and         |
|           | 43498423**  | applied      | developmental toxicity -   |
| Deve      |             | dermally at  | ddY): 1.7% (HDT)           |
| lopmental | Masuda et   | a level of   |                            |
| Toxicity  | al. (1974)  | 0.5 ml. The  | NOEL (maternal toxicity -  |
| (rodent)  | Effects of  | ICR-JCL      | ICR-JCL): 2.55%            |
|           | LAS Applied | strain       |                            |
|           | Dermally to | received     | NOEL (developmental        |
|           | Pregnant    | doses of 0,  | toxicity - ICR-JCL): 1.7%  |
|           | Mice on the | 0.85, 1.7,   |                            |
|           | Development | 2.55, and    | At 3.4% LAS, maternal body |
|           | of their    | 3.4%         | weight and the absolute    |
|           | Fetuses.    | solutions    | weight of liver, kidney,   |
|           | 15:         | daily from   | spleen were significantly  |
|           | 349-355.    | days 1 to 13 | increased over control..   |
|           |             | of gestation | Pregnancy rates were       |
|           | **A         | and the ddY  | significantly less (33.35) |
|           | cceptable** | strain       | compared to controls       |
|           |             | received     | (69%).                     |
|           | Guideline   | doses of 0,  |                            |
|           |             | 0.017, 0.17, | The number of              |
|           |             | and 1.7%     | implantations, live        |
|           |             | solutions    | fetuses, sex ratio, dead   |
|           |             | daily from   | or resorbed fetuses,       |
|           |             | days 2 to 14 | placenta weight and        |
|           |             | of           | external malformations     |
|           |             | gestation.   | were comparable with       |
|           |             |              | control. Fetal body        |
|           |             | Mouse        | weights of 2.55% and 3.4%  |
|           |             | (ICR-JCL     | LAS-treated groups were    |
|           |             | strain and   | significantly less than    |
|           |             | ddY strain)  | controls.                  |
|           |             |              |                            |
|           |             | Purity: Not  |                            |
|           |             | Reported     |                            |
+-----------+-------------+--------------+----------------------------+
| 870.3700a | **MRID      | LAS (0.1 ml  | Development was retarded   |
|           | 43498424    | ) was        | and cleavage of eggs was   |
| Deve      | and         | applied at a | interrupted. Significantly |
| lopmental | 43498425**  | c            | higher numbers of embryos  |
| Toxicity  |             | oncentration | were found to be deformed  |
| (rodent)  | Nomura, T   | of 20% to    | in the LAS group in        |
|           | et al.      | the dorsal   | comparison to controls,    |
|           | (1980) The  | skin of      | and most of these embryos  |
|           | Synthetic   | pregnant     | were in the morula stage,  |
|           | Surfactants | mice during  | whereas they were mostly   |
|           | AS and LAS  | the          | in the last blastocyst     |
|           | Interrupt   | pre-         | stage in controls.         |
|           | Pregnancy   | implantation |                            |
|           | in Mice.    | period twice | Some dead, deformed, and   |
|           | Life        | a day from   | growth-retarded embryos    |
|           | Sciences,   | day 0 to day | were observed in the       |
|           | 26: 49-54.  | 3 of         | treated group. Although    |
|           | (HERA)      | pregnancy    | the authors stated that    |
|           |             |              | these effects were not due |
|           | Nomura, T.  | Female       | to maternal toxicity since |
|           | et al.      | ICR/Jcl      | no maternal organs were    |
|           | (1987)      | Mouse,       | affected, this statement   |
|           | Killing of  |              | is probably not correct in |
|           | Prei        | 9-10 weeks   | view of the high           |
|           | mplantation | old          | concentration of LAS and   |
|           | Mouse       |              | its irritation effects. A  |
|           | Embryos by  | Purity: 20%  | secondary effect due to    |
|           | AS and LAS. |              | maternal toxicity appears  |
|           | Mutation    |              | much more likely.          |
|           | Research    |              |                            |
|           | 190: 25-29. |              |                            |
|           | (HERA)      |              |                            |
|           |             |              |                            |
|           | **A         |              |                            |
|           | cceptable** |              |                            |
|           |             |              |                            |
|           | Guideline   |              |                            |
+-----------+-------------+--------------+----------------------------+
| 870.3700a | **MRID      | LAS was      | NOAEL (rat - maternal):    |
|           | 43498426**  | administered | 300 mg/kg bw/d             |
| Deve      |             | by gavage on |                            |
| lopmental | Palmer et   | days 6-15 of | NOAEL (mouse - maternal):  |
| Toxicity  | al. (1975)  | pregnancy in | 2.0 mg/kg bw/d (However,   |
| (rodent)  | Assessment  | rats and     | there is a large           |
|           | of the      | mice and     | difference between this    |
|           | Teratogenic | days 6-18 of | dose and the next highest  |
|           | Potential   | pregnancy in | dose of 300 mg/kg bw/d,    |
|           | of          | rabbits at   | this study does not allow  |
|           | S           | doses of     | determination of a         |
|           | urfactants, | 0.2, 2, 300, | reliable maternal NOAEL    |
|           | (Part I),   | and 600      | for mice)                  |
|           | Toxicology  | mg/kg bw/d   |                            |
|           | 3: 91-106.  |              | NOAEL (rabbit - maternal): |
|           |             | 20 CD Rats,  | 2.0 mg/kg b/d (However,    |
|           | **A         | 20 CD-1      | the study does not allow   |
|           | cceptable** | Mice, and 13 | determination of reliable  |
|           |             | New Zealand  | NOAELs, given the large    |
|           | Guideline   | White        | difference between the     |
|           |             | Rabbits      | maternal no-effects doses  |
|           |             |              | of 2 mg/kg bw/d and the    |
|           |             | Purity: 17%  | 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 | **MRID      | LAS was      | LOEL (maternal toxicity,   |
|           | 43511403**  | administered | mice): 0.3% (50 mg/kg/d)   |
| Deve      |             | pe           |                            |
| lopmental | Palmer, et  | rcutaneously | LOEL (maternal toxicity,   |
| Toxicity  | al. (1975)  | to shaved    | rats): 3.0% (60 mg/kg/d)   |
| (rodent)  | Assessment  | skin at      |                            |
|           | of the      | solutions of | LOEL (maternal toxicity,   |
|           | Teratogenic | 0.03%, 0.3%, | rabbits): 0.3% (9.0        |
|           | Potential   | and 3%       | mg/kg/d)                   |
|           | of          | during       |                            |
|           | S           | pregnancy on | NOEL (maternal toxicity,   |
|           | urfactants, | days 2-13 in | mice): 0.03% (5.0 mg/kg/d) |
|           | (Part       | mice, 2-15   |                            |
|           | III) -      | in rats, and | NOEL (maternal toxicity,   |
|           | Dermal      | 1-16 in      | rats): 0.3% (6.0 mg/kg/d)  |
|           | Application | rabbits.     |                            |
|           | of LAS and  | Dosages      | NOEL (maternal toxicity,   |
|           | Soap.       | employed     | rabbits): 0.03% ((0.9      |
|           | Huntingdon  | were 0.5     | mg/kg/d)                   |
|           | Research    | ml/rat or    |                            |
|           | Centre,     | mouse/day    | LOEL (developmental        |
|           | Huntingdon, | and 10       | toxicity): 0.3% (50        |
|           | Great       | m            | mg/kg/d)                   |
|           | Britain.    | l/rabbit/day |                            |
|           | Study No.   |              | LOEL (developmental        |
|           | DDBSA       | CD-1 Mice    | toxicity): 3.0% (60        |
|           | JV-RP4-029. | (20/group),  | mg/kg/d)                   |
|           | Toxicology  | CD Rats      |                            |
|           | 4: 171-181. | (20/group),  | LOEL (developmental        |
|           |             | N2W Rabbits  | toxicity): 3.0% (90        |
|           | **A         | (13/group)   | mg/kg/d)                   |
|           | cceptable** |              |                            |
|           |             | Purity:      | NOEL (developmental        |
|           | Guideline   | 0.03%, 0.3%, | toxicity): 0.03% (5.0      |
|           |             | and 3%       | 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 | Sato et al. | LAS was      | NOAEL (maternal): 110      |
|           | (1972)      | applied to   | mg/kg bw/d                 |
| Deve      | Studies on  | the skin of  |                            |
| lopmental | the         | female mice  | No abnormalities were seen |
| Toxicity  | Toxicity of | daily on     | in the dam or foetuses.    |
| (rodent)  | Synthetic   | days 0       |                            |
|           | Detergents: | through 13   |                            |
|           | (III),      | of pregnancy |                            |
|           | Examination | with a       |                            |
|           | of          | single LAS   |                            |
|           | Teratogenic | dose of 110  |                            |
|           | Effects of  | mg/kg bw/d.  |                            |
|           | A           | Control      |                            |
|           | lkylbenzene | group not    |                            |
|           | Sulfonates  | specified.   |                            |
|           | Spread on   |              |                            |
|           | the Skin of | F Mouse      |                            |
|           | Mice. Ann.  |              |                            |
|           | Rep. Tokyo  | Purity: Not  |                            |
|           | Metrop.     | Reported     |                            |
|           | Res. Lab.   |              |                            |
|           | Public      |              |                            |
|           | Health 24:  |              |                            |
|           | 441-448.    |              |                            |
|           | (HERA)      |              |                            |
|           |             |              |                            |
|           | **Open      |              |                            |
|           | L           |              |                            |
|           | iterature** |              |                            |
+-----------+-------------+--------------+----------------------------+
| 870.3700a | Shiobara    | LAS was      | LOAEL (maternal): 10 mg/kg |
|           | S., Imahori | administered | bw/d                       |
| Deve      | A. (1976)   | by gavage at |                            |
| lopmental | Effects of  | doses of 10, | NOAEL (fetuses): 300 mg/kg |
| Toxicity  | LAS Orally  | 100, and 300 | bw/d                       |
| (rodent)  | A           | mg/kg bw/d   |                            |
|           | dministered | at day 6     | 1\. Marked maternal and    |
|           | to Pregnant | through 15   | embryonic toxicities, such |
|           | Mice on the | of gestation | as maternal death,         |
|           | Pregnant    |              | premature delivery, total  |
|           | Mice and    | ICR-SLC      | litter loss and high fetal |
|           | their       | Mouse        | death rate, were observed  |
|           | Fetuses.    | (25-33/dose) | at 300 mg/kg group.        |
|           | J.Food Hyg. |              |                            |
|           | Soc. Jpn.   | Purity: Not  | 2\. Slight suppression of  |
|           | (Shokuhin   | Reported     | maternal body weight gain  |
|           | Eiseigaku   |              | and slight body weight     |
|           | Zasshi)     |              | suppression of live        |
|           | 17(4):      |              | fetuses were observed in   |
|           | 295-301.    |              | each treated group.        |
|           |             |              |                            |
|           | **Open      |              | 3\. External malformations |
|           | L           |              | such as cleft palate and   |
|           | iterature** |              | 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 | Takahashi   | LAS doses of | NOAEL (maternal): 40 mg/kg |
|           | et al.      | 40, and 400  | bw/d                       |
| Deve      | (1975)      | mg/kg bw/d   |                            |
| lopmental | Ter         | were         | NOAEL (fetuses): 400 mg/kg |
| Toxicity  | atogenicity | administered | bw/d                       |
| (rodent)  | of Some     | daily from   |                            |
|           | Synthetic   | day 0 to day | At 400 mg/kg bw/day, the   |
|           | Detergent   | 6 of         | pregnancy rate was 46.2%   |
|           | and LAS.    | pregnancy or | compared to 92.9% in the   |
|           | Ann. Rep.   | from day 7   | controls. There was no     |
|           | Tokyo       | to 13 of     |                            |
|           | Metrop.     | pregnancy by | increase in malformations. |
|           | Res. Lab.   | gavage       | Although no information on |
|           | Public      |              | maternal toxicity is       |
|           | Health      | Mouse        | available, it appears      |
|           | 26(2):      | (            |                            |
|           | 67-78.      | 13-14/group) | likely that maternal       |
|           | (HERA)      |              | toxicity was present at    |
|           |             | Purity: not  | the high dose group.       |
|           | **Open      | reported     |                            |
|           | L           |              |                            |
|           | iterature** |              |                            |
+-----------+-------------+--------------+----------------------------+
| 870.3700a | Tiba et al. | LAS was      | NOAEL (maternal): 780      |
|           | (1976)      | administered | mg/kg bw/d                 |
| Deve      | Effects of  | in the diet  |                            |
| lopmental | LAS on Dam, | at doses of  | NOAEL (fetuses): 780 mg/kg |
| Toxicity  | Fetus, and  | 80 and 780   | bw/d                       |
| (rodent)  | Newborn     | mg/kg bw/d   |                            |
|           | Rat. J.     | from day 0   | At 780 mg/kg bw/day there  |
|           | Food Hyg.   | to 20 of     | were no abnormalities in   |
|           | Soc. Jpn.   | gestation    | the body weight gains of   |
|           | (Shokuhin   |              | the dams, or in the        |
|           | Eiseigaku   | F Rat        | occurrence and maintenance |
|           | Zassh)      | (16/dose)    | of pregnancy. The values   |
|           | 17(1):      |              | of the litter parameters   |
|           | 66-71.      | Purity: Not  | did not differ from those  |
|           | (HERA)      | Reported     | of the controls and there  |
|           |             |              | was no evidence of         |
|           | **Open      |              | teratogenicity. The number |
|           | L           |              | of offsprings was rather   |
|           | iterature** |              | 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.            |
+-----------+-------------+--------------+----------------------------+
| **Rep     |             |              |                            |
| roduction |             |              |                            |
| T         |             |              |                            |
| oxicity** |             |              |                            |
+-----------+-------------+--------------+----------------------------+
| 870.3800  | **MRID      | LAS was      | NOAEL Parental: 250 mg/kg  |
|           | 43498416**  | administered | bw/day                     |
| Rep       |             | in the diet  |                            |
| roduction | Buehler,    | at doses of  | NOAEL Offspring: 50        |
|           | E.,         | 0, 0.02,     | mg/kg/d.                   |
|           | Newmann,    | 0.1, and     |                            |
|           | E., and     | 0.5% ,       | The LOAEL of 250 mg/kg/day |
|           | King, W.    | equivalent   | in the offspring is due to |
|           | (1971) Two  | to (0, 10,   | slight (non-significant)   |
|           | Year        | 50, 250      | changes in hematology and  |
|           | Feeding and | mg/kg        | histopathology and slight  |
|           | R           | bw/day) for  | decrease in day 21 body    |
|           | eproduction | 84 days.     | weights.                   |
|           | Study in    |              |                            |
|           | Rats with   | Weanling     |                            |
|           | Linear      | Charles      |                            |
|           | A           | River CD Rat |                            |
|           | lkylbenzene | (            |                            |
|           | Sulfonate   | 20/sex/dose) |                            |
|           | (LAS). Tox. |              |                            |
|           | Appl.       | Purity:      |                            |
|           | Pharm. 18:  | 98.1%        |                            |
|           | 83-91.      |              |                            |
|           | (HERA)      |              |                            |
|           |             |              |                            |
|           | **A         |              |                            |
|           | cceptable** |              |                            |
|           |             |              |                            |
|           | Guideline   |              |                            |
+-----------+-------------+--------------+----------------------------+
| 870.3800  | Endo et al. | LAS was      | NOAEL: \> 70 mg/kg (only   |
|           | (1980)      | administered | dose tested)               |
| Rep       | Studies of  | at 70 mg/kg  |                            |
| roduction | the Chronic | bw/day in    | No effects of LAS          |
|           | Toxicity    | the drinking | administration were        |
|           | and         | water in a   | observed                   |
|           | Ter         | four         |                            |
|           | atogenicity | generation   |                            |
|           | of          | rat study.   |                            |
|           | Synthetic   |              |                            |
|           | S           | M/F Wistar   |                            |
|           | urfactants, | Rat          |                            |
|           | Ann. Rep.   |              |                            |
|           | Tokyo       | Purity: Not  |                            |
|           | Metrop.     | Reported     |                            |
|           | Res. Inst.  |              |                            |
|           | Environ.    |              |                            |
|           | Prot.       |              |                            |
|           | (Tokyo      |              |                            |
|           | Kogai       |              |                            |
|           | Kenkyujo    |              |                            |
|           | Nempo),     |              |                            |
|           | 236-246.    |              |                            |
|           | (HERA)      |              |                            |
|           |             |              |                            |
|           | **Open      |              |                            |
|           | L           |              |                            |
|           | iterature** |              |                            |
+-----------+-------------+--------------+----------------------------+
| 870.3800  | Palmer et   | A commercial | NOAEL: 170 mg/kg bw/d      |
|           | al. (1974)  | light duty   |                            |
| Rep       | Effect of   | liquid       | Among parental animals     |
| roduction | CLD         | detergent of | over the three             |
|           | R           | LAS (17%)    |                            |
|           | eproductive | and alkyl    | generations there were no  |
|           | Function of | ethoxylate   | signs of adverse effects   |
|           | Multiple    | sulphate     | of treatment. Food         |
|           | Generations | (7%) was     | consumption and bodyweight |
|           | in the Rat, | continuously |                            |
|           | Report      | administered | changes showed no          |
|           | LF          | in the diet  | consistent relationship to |
|           | O10/731029, | for three    | dosage. Necroscopy         |
|           | Unpublished | generations  | revealed no changes due to |
|           | results.    | 60 days      | treatment. The mating      |
|           | (HERA)      | prior to     | performance, the pregnancy |
|           |             | mating at    | rate and the duration of   |
|           | **Open      | co           | gestation were unaffected. |
|           | L           | ncentrations |                            |
|           | iterature** | of 0, 40,    | Among litter parameters,   |
|           |             | 200, and     | organ weight               |
|           |             | 1000 mg/kg   |                            |
|           |             | bw/d. The    | analysis, histopathology   |
|           |             | corresonding | and skeletal staining of   |
|           |             | ad           | representative young from  |
|           |             | ministration | the F3b generation         |
|           |             | of LAS was   |                            |
|           |             | of 0, 6.8,   | revealed no changes that   |
|           |             | 34, and 170  | could be conclusively      |
|           |             | mg/kg bw/d.  | related to treatment.      |
|           |             |              |                            |
|           |             | Rat          |                            |
|           |             |              |                            |
|           |             | Purity: 17%  |                            |
+-----------+-------------+--------------+----------------------------+
| **Chronic |             |              |                            |
| T         |             |              |                            |
| oxicity** |             |              |                            |
+-----------+-------------+--------------+----------------------------+
| 870.4100a | Taniguchi   | LAS were     | Treatment had no effect on |
| Chronic   | et al.      | applied to   | organ weights or           |
| Toxicity  | (1978)      | the dorsal   | histopathological          |
| (rodent)  | Results of  | skin of rats | appearance, and there was  |
|           | Studies on  | three times  | no evidence of toxicity or |
|           | Synthetic   | per week at  | carcinogenicity.           |
|           | Detergents. | doses of 1,  |                            |
|           | Tokyo,      | 5, or 25     |                            |
|           | Science and | mg/rat for   |                            |
|           | Technology  | 24 months.   |                            |
|           | Agency,     | Each         |                            |
|           | Research    | application  |                            |
|           | and         | was washed   |                            |
|           | C           | from the     |                            |
|           | oordination | skin with    |                            |
|           | Bureau, pp. | warm water   |                            |
|           | 18-54. (WHO | after 24     |                            |
|           | 1996)       | hours.       |                            |
|           |             |              |                            |
|           | **Open      | SLC-Wistar   |                            |
|           | L           | Rats         |                            |
|           | iterature** |              |                            |
|           |             | Purity:      |                            |
|           |             | 19.7% a.i.   |                            |
+-----------+-------------+--------------+----------------------------+
| 870.3100  | Yoneyama et | LAS was      | LOAEL: 500 mg/kg bw/d (in  |
|           | al. (1976)  | administered | diet)                      |
| Chronic   | Subacute    | in the diet  |                            |
| Toxicity  | Toxicity of | at           | NOAEL: 250 mg/kg bw/d (in  |
|           | LAS, Ann.   | co           | water)                     |
| (rodent)  | Rep. Tokyo  | ncentrations |                            |
|           | Metrop.     | of 500 and   | LAS in diet: in the mice   |
|           | Res. Lab.   | 1000 mg/kg   | given 500 mg/kg bw/day,    |
|           | Public      | bw/d and in  | body weight gain was not   |
|           | H           | drinking     | suppressed, but the        |
|           | ealth27(2): | water at     |                            |
|           | 105-112,    | co           | weight of the liver        |
|           | See: IPCS,  | ncentrations | increased in male and      |
|           | 1996.       | of 100, 250, | female mice. Enzymatic     |
|           | (HERA)      | 600 mg/kg    | examinations revealed      |
|           |             | bw/d for     | significant                |
|           | **Open      | males and    |                            |
|           | L           | 100, 250,    | decreases in LDH of the    |
|           | iterature** | 900 mg/kg    | liver and in acid          |
|           |             | bw/d for     | phosphatase of the kidneys |
|           |             | females for  | in the male mice.          |
|           |             | 9 months     |                            |
|           |             |              | LAS in drinking water:     |
|           |             | Mouse (8 or  | body weight was depressed  |
|           |             | 9/sex/dose)  | at the highest dose for    |
|           |             |              | male and females, increase |
|           |             | Purity: Not  | in liver weight in         |
|           |             | Reported     | females, significant       |
|           |             |              | decreases in renal         |
|           |             |              | Na,K-ATPase.               |
+-----------+-------------+--------------+----------------------------+
| 870.3100  | Yoneyama et | LAS was      | NOAEL: 85 mg/kg bw/d       |
|           | al. (1976)  | administered |                            |
| Chronic   | Subacute    | for 9 months | LOAEL: 145 mg/kg bw/d      |
| Toxicity  | Toxicity of | in the       |                            |
|           | LAS, Ann.   | drinking     | Haematological examination |
| (rodent)  | Rep. Tokyo  | water at     | revealed no significant    |
|           | Metrop.     | doses of 85, | changes in any             |
|           | Res. Lab.   | 145, 430     | experimental group and no  |
|           | Public      | mg/kg bw/day | organ                      |
|           | H           |              |                            |
|           | ealth27(2): | M/F Wistar   | weight changes were        |
|           | 105-112,    | Rat          | observed. Body weight gain |
|           | See: IPCS,  |              | was suppressed in the      |
|           | 1996.       | Purity: Not  | males of the highest dose  |
|           | (HERA)      | Reported     |                            |
|           |             |              | group and also             |
|           | **Open      |              | serum-biochemical and      |
|           | L           |              | enzymatic parameters of    |
|           | iterature** |              | 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 | Yoneyama et | Tec          | NOAEL: 0.07% (40 mg/kg     |
| Chronic   | al. (1972)  | hnical-grade | bw/day)                    |
| Toxicity  | Studies on  | LAS was      |                            |
| (rodent)  | the         | administered | At 1.8%, diarrhea,         |
|           | Toxicity of | in the feed  | decrease in body weight    |
|           | Synthetic   | for 6 months | gain and tissue damage in  |
|           | Detergents. | at a         | caecum liver and kidney    |
|           | (II)        | c            | were observed. The damage  |
|           | Subacute    | oncentration | to the kidney was          |
|           | Toxicity of | of 0, 0.07,  | especially remarkable.     |
|           | Linear and  | 0.2, 0.6, or |                            |
|           | Branched    | 1.8%         | At 0.6% of the LAS or ABS, |
|           | Alkyl       |              | the adverse effects        |
|           | Benzene     | Wistar SLC   | observed were a slight     |
|           | Sulfonates  | Strain Rat   | decrease of body weight,   |
|           | in Rats.    | (            | increase of ceacum weight, |
|           | Ann Rep     | 10/sex/dose) | increased activity of      |
|           | Tokyo       |              | alkaline phosphatase,      |
|           | Metrop Res  | Purity: Not  | decrease of total protein  |
|           | Lab Public  | Reported     | in blood, and the tissue   |
|           | Health, 24: |              | damage in the kidney.      |
|           | 409-440.    |              |                            |
|           |             |              | At 0.2% of the LAS or ABS, |
|           | **Open      |              | an increase of caecum      |
|           | L           |              | weight and a slight damage |
|           | iterature** |              | to the kidney were         |
|           |             |              | observed.                  |
+-----------+-------------+--------------+----------------------------+
| *         |             |              |                            |
| *Carcinog |             |              |                            |
| enicity** |             |              |                            |
+-----------+-------------+--------------+----------------------------+
| 870.4200a | **MRID      | LAS was      | Negative at 250 mg/kg/day  |
| Onc       | 43498416**  | administered | (HDT)                      |
| ogenicity |             | in the diet  |                            |
| (Rat)     | Buehler,    | at doses of  |                            |
|           | E.,         | 10, 50, and  |                            |
|           | Newmann,    | 250          |                            |
|           | E., and     | mg/kg/day    |                            |
|           | King, W.    | for 2 years  |                            |
|           | (1971) Two  |              |                            |
|           | Year        | Weanling     |                            |
|           | Feeding and | Charles      |                            |
|           | R           | River CD     |                            |
|           | eproduction | Rats         |                            |
|           | Study in    | (5           |                            |
|           | Rats with   | 0/sex/group) |                            |
|           | Linear      |              |                            |
|           | A           | Purity: Not  |                            |
|           | lkylbenzene | Reported     |                            |
|           | Sulfonate   |              |                            |
|           | (LAS). Tox. |              |                            |
|           | Appl.       |              |                            |
|           | Pharm. 18:  |              |                            |
|           | 83-91.      |              |                            |
|           | (HERA)      |              |                            |
|           |             |              |                            |
|           | **A         |              |                            |
|           | cceptable** |              |                            |
|           |             |              |                            |
|           | Guideline   |              |                            |
+-----------+-------------+--------------+----------------------------+
| 870.4200a | Endo et al. | LAS was      | The administration of LAS  |
|           | (1980)      | administered | had no effect on the       |
| Onc       | Studies of  | in the       | intake of water,           |
| ogenicity | the Chronic | drinking     | mortality, body weight     |
| (Rat)     | Toxicity    | water at the | gain, or general           |
|           | and         | dose of 200  | condition. In pathological |
|           | Ter         | mg/kg bw/d   | examinations, looseness,   |
|           | atogenicity |              | atrophy, and fatty change  |
|           | of          | 62 M/F       | of the hepatic cells in    |
|           | Synthetic   | Wistar Rat   | the liver were found in    |
|           | S           |              | the experimental control   |
|           | urfactants, | Purity:      | group at 6 months,         |
|           | Ann. Rep.   | 38.74% a.i.  | together with significant  |
|           | Tokyo       |              | increases in GOT, GTP and  |
|           | Metrop.     |              | bilirubin. In              |
|           | Res. Inst.  |              | hematological examinations |
|           | Environ.    |              | no effects due to LAS were |
|           | Prot.       |              | observed.                  |
|           | (Tokyo      |              |                            |
|           | Kogai       |              |                            |
|           | Kenkyujo    |              |                            |
|           | Nempo),     |              |                            |
|           | 236-246.    |              |                            |
|           | (HERA)      |              |                            |
|           |             |              |                            |
|           | **Open      |              |                            |
|           | L           |              |                            |
|           | iterature** |              |                            |
+-----------+-------------+--------------+----------------------------+
| 870.4200a | Fujii et    | LAS was      | Histopathological          |
|           | al. (1977)  | administered | examination revealed that  |
| Onc       | P           | in the feed  | there was no evidence of a |
| ogenicity | athological | at a         | treatment-related effect   |
| (Rat)     | Examination | c            | on any tissue examined.    |
|           | of Rats Fed | oncentration | Whereas a variety of       |
|           | with LAS    | of 0.04,     | tumors were observed in    |
|           | for their   | 0.16, and    | both linear alkylbenzene   |
|           | Lifespan,   | 0.60% for 24 | sulfonate treated and      |
|           | Ann. Rep.   | months or    | control rats, none was     |
|           | Tokyo       | lifespan     | attributed for the         |
|           | Metrop.     |              | exposure to linear         |
|           | Res. Lab.   | Wistar       | alkylbenzene sulfonate.    |
|           | Public      | Weanling Rat | There was no relationship  |
|           | Health      | (            | among the dosage groups,   |
|           | 28(2):      | 15/sex/dose) | sex, type of tumor, or the |
|           | 85-108.     |              | site of occurrence.        |
|           | (HERA)      | Purity: Not  |                            |
|           |             | Reported     |                            |
|           | Yoneyama et |              |                            |
|           | al. (1977)  |              |                            |
|           | Toxicity of |              |                            |
|           | LAS by      |              |                            |
|           | Dietary     |              |                            |
|           | Adm         |              |                            |
|           | inistration |              |                            |
|           | for         |              |                            |
|           | Life-Span   |              |                            |
|           | to Rats,    |              |                            |
|           | Ann. Rep.   |              |                            |
|           | Tokyo       |              |                            |
|           | Metrop.     |              |                            |
|           | Res. Lab.   |              |                            |
|           | Public      |              |                            |
|           | Health      |              |                            |
|           | 28(2):      |              |                            |
|           | 73-84.      |              |                            |
|           | (HERA)      |              |                            |
|           |             |              |                            |
|           | **Open      |              |                            |
|           | L           |              |                            |
|           | iterature** |              |                            |
+-----------+-------------+--------------+----------------------------+
| 870.4200a | **MRID      | For 560      | In Groups I and I\', the   |
|           | 43498420**  | days; Group  | presence of SDDBS shifts   |
| Onc       |             | I (79 rats): | the incidence of benign    |
| ogenicity | Takahasi et | 1 mg 4-NQO   | papillomas to malignant    |
| (Rat)     | al. (1969)  | and 80 mg    | papillomas of the          |
|           | Effect of   | SDDBS 2-3x   | forestomach and the        |
|           | Alkylbenze  | per week for | incidence of               |
|           | nesulfonate | 18 weeks;    | adenocarcinoma and sarcoma |
|           | as a        | Group I\'    | of the stomach were        |
|           | Vehicle for | (17 rats):   | increased in comparison to |
|           | 4-          | same as      | Group II with only 4-NQO.  |
|           | Nitroquinol | Group 1, but | The administration of      |
|           | ine-1-Oxide | fasted for   | SDDBS by itself has no     |
|           | on Gastric  | 12 hours     | effect on gastric tumors   |
|           | Car         | prior to     | (Group III). The study     |
|           | cinogenesis | dosing,;     | authors concluded that the |
|           | in Rats.    | Group II (37 | increased carcinogenicity  |
|           | GANN: 8,    | rats): 1 mg  | produced by SDDBS was due  |
|           | 241-261.    | 4-NQO only;  | to the better uptake of    |
|           |             | Group III    | 4-NQO via LAS\'s           |
|           | **A         | (28 rats):   | surfactive/detersive       |
|           | cceptable** | 80 mg SDDBS  | effects on the protective  |
|           |             | only         | mucous barrier which is    |
|           | Guideline   |              | normally found in the      |
|           |             | 97 M Wistar  | glandular stomach and      |
|           |             | Rats         | other gastric compartments |
|           |             |              | of the rat. The effect of  |
|           |             | Purity: Not  | SDDBS was physical rather  |
|           |             | Reported     | than chemical in promoting |
|           |             |              | the increased              |
|           |             |              | tumorigenicity.            |
+-----------+-------------+--------------+----------------------------+
| 870.4200a | **MRID      | Rats were    | Survival: Mortality was    |
|           | 43498419**  | divided into | 59% in Group I, 31% in     |
| Onc       |             | three groups | Group II, and 23% in Group |
| ogenicity | Takahasi et | and gavaged  | III                        |
| (Rat)     | al. (1970)  | with the     |                            |
|           | Effect of   | following    | Tumors: Group III - no     |
|           | 4-          | regimen for  | gastric tumors; Group II - |
|           | Nitroquinol | 560 days:    | 9 benign papillomas of     |
|           | ine-1-Oxide | Group I (37  | forestomach; Group I - 8   |
|           | with        | rats) - 1 mg | benign papillomas of       |
|           | Alkylbenze  | 4-NQO + 80   | forestomach, 2 malignant   |
|           | nesulfonate | mg SDDBS +   | papillomas of forestomach, |
|           | on Gastric  | 20 mg        | 1 hemangiosarcoma of       |
|           | Car         | ethanol in a | forestomach. In glandular  |
|           | cinogenesis | 1 ml gavage  | stomach, 2                 |
|           | in Rats.    | for 18       | adenocarcinomas, 1         |
|           | GANN: 61,   | weeks; Group | hemangiosarcoma, 1         |
|           | 27-33.      | II (13       | hemangioma, 5 squamous     |
|           |             | rats) -      | cell carcinomas, and 2     |
|           | **A         | 4-NQO and    | rats exhibited atrophic    |
|           | cceptable** | ethanol for  | gastritis.                 |
|           |             | 18 weeks;    |                            |
|           | Guideline   | Group III    | The increased toxicity in  |
|           |             | (13 rats) -  | Group I produced increased |
|           |             | SDDBS +      | mortality and increased    |
|           |             | ethanol for  | numbers of malignant       |
|           |             | 18 weeks     | tumors. The role of SDDBS  |
|           |             |              | in the tumorigenesis of    |
|           |             | 64 M         | 4-NQO was to promote       |
|           |             | Motoyama     | increased absorption of    |
|           |             | Strain Rat   | 4-NQO through the          |
|           |             |              | forestomach and glandular  |
|           |             | Purity: Not  | stomach.                   |
|           |             | Reported     |                            |
+-----------+-------------+--------------+----------------------------+
| 870.4200a | **MRID      | SDDBS was    | Survivial was 100% in      |
|           | 43498421,   | administered | Groups I, III, and IV, and |
| Onc       | -22**       | to 5 groups  | 93% and 94% in Groups V    |
| ogenicity |             | of rats: (I) | and II, respectively.      |
| (Rat)     | Takahasi et | 13 rats      |                            |
|           | al. (1973)  | received     | The Group I and II rats    |
|           | C           | 0.1g of      | had more tumors than the   |
|           | arcinogenic | MNNG + 4000  | controls (Group V),        |
|           | Effect of   | mg Tween 60  | whereas, the rats in Group |
|           | N-Me        | per L of     | III, (\"hard\" SDDBS, and  |
|           | thyl-N\'-Ni | drinking     | particularly, Group IV     |
|           | tro-N-Nitro | water for 36 | (linear \"soft\" SDDBS)    |
|           | soguanidine | weeks; (II)  | had the fewest tumors in   |
|           | with        | 16 rats      | comparison to controls.    |
|           | Various     | received 0.1 |                            |
|           | Kinds of    | g MNNG +     |                            |
|           | Surfactant  | 2000 mg      |                            |
|           | in the      | nonipol per  |                            |
|           | Glandular   | L of         |                            |
|           | Stomach of  | drinking     |                            |
|           | Rats.       | water for 36 |                            |
|           |             | weeks; (III) |                            |
|           | **A         | 15 rats      |                            |
|           | cceptable** | received 0.1 |                            |
|           |             | g of MNNG +  |                            |
|           | Guideline   | 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     |                            |
+-----------+-------------+--------------+----------------------------+
| 870.4200a | Tiba S      | LAS was      | There were no changes due  |
|           | (1972)      | administered | to the administration of   |
| Onc       | Studies on  | in drinking  | LAS in regard to growth,   |
| ogenicity | the Acute   | water for 2  | mortality, the weight of   |
| (Rat)     | and Chronic | years at     | major organs, or           |
|           | Toxicity of | doses of 20, | histopathological findings |
|           | LAS, J.     | 100, and 200 |                            |
|           | Food Hyg.   | mg/kg bw/d   |                            |
|           | Soc. Jpn.   |              |                            |
|           | (Shokuhin   | M Wistar Rat |                            |
|           | Eiseigaku   | (20/group)   |                            |
|           | Zasshi)     |              |                            |
|           | 13(6):      | Purity: Not  |                            |
|           | 509-516.    | Reported     |                            |
|           | (HERA)      |              |                            |
|           |             |              |                            |
|           | **Open      |              |                            |
|           | L           |              |                            |
|           | iterature** |              |                            |
+-----------+-------------+--------------+----------------------------+
| **Mutag   |             |              |                            |
| enicity** |             |              |                            |
+-----------+-------------+--------------+----------------------------+
| 870.5100  | Huls,       | LAS was      | Negative results           |
| Bacterial | Report No.  | tested at    |                            |
| reverse   | AM-93/12,   | 8-5000       |                            |
| mutation  | Unpublished | ug/plate     |                            |
| test      | data, 1993. | with and     |                            |
|           | (As cited   | without      |                            |
|           | in          | metabolic    |                            |
|           | HERA-2004)  | activation.  |                            |
|           |             | The          |                            |
|           | **Open      | cytotoxicity |                            |
|           | L           | c            |                            |
|           | iterature** | oncentration |                            |
|           |             | was \>5000   |                            |
|           |             | ug/plate.    |                            |
|           |             |              |                            |
|           |             | Salmonella   |                            |
|           |             | typhimurium, |                            |
|           |             | strains TA   |                            |
|           |             | 98, TA 100,  |                            |
|           |             | TA 1535, TA  |                            |
|           |             | 1537, and TA |                            |
|           |             | 1538         |                            |
|           |             |              |                            |
|           |             | Purity: Not  |                            |
|           |             | Reported     |                            |
+-----------+-------------+--------------+----------------------------+
| 870.5100  | **MRID      | SDDBS was    | Negative (both with and    |
| Bacterial | 43498429**  | tested at    | without S-9 metabolic      |
| reverse   |             | cytotoxic    | activation)                |
| mutation  | Inoue et    | levels or    |                            |
| test      | al. (1980)  | limit        |                            |
|           | Studies of  | co           |                            |
|           | In Vitro    | ncentrations |                            |
|           | Cell        | of           |                            |
|           | Tra         | 2,000-30,000 |                            |
|           | nsformation | ug/plate for |                            |
|           | and         | 2 days       |                            |
|           | M           | (Salmonella) |                            |
|           | utagenicity | or 8 days    |                            |
|           | by          | (SHE)        |                            |
|           | Surfactants |              |                            |
|           | and other   | Strain:      |                            |
|           | Compounds,  | Salmonella   |                            |
|           | Food.       | t            |                            |
|           | Cosmet.     | yphimurium - |                            |
|           | Toxicol 18: | TA 98 and TA |                            |
|           | 289-296.    | 100 cells    |                            |
|           | (HERA)      | and          |                            |
|           |             | Embryonic    |                            |
|           | **A         | Syrian       |                            |
|           | cceptable** | Golden       |                            |
|           |             | Hamster      |                            |
|           | Guideline   | cells (SHE)  |                            |
|           |             |              |                            |
|           |             | Purity: Not  |                            |
|           |             | Reported     |                            |
+-----------+-------------+--------------+----------------------------+
| 870.5100  | Sunakawa et | LAS was      | Negative Results           |
| Bacterial | al. (1981)  | tested at up |                            |
| reverse   | Studies on  | to 500       |                            |
| mutation  | the         | ug/plate     |                            |
| test      | M           |              |                            |
|           | utagenicity | Salmonella   |                            |
|           | of          | typhimurium  |                            |
|           | Surfactants |              |                            |
|           | Following   | Purity: Not  |                            |
|           | Activation  | Reported     |                            |
|           | with        |              |                            |
|           | Various     |              |                            |
|           | Liver       |              |                            |
|           | Homogenates |              |                            |
|           | (S-9) and   |              |                            |
|           | M           |              |                            |
|           | utagenicity |              |                            |
|           | in the      |              |                            |
|           | Presence of |              |                            |
|           | Norharman,  |              |                            |
|           | Hyg. Chem.  |              |                            |
|           | (Eisei      |              |                            |
|           | Kagaku)     |              |                            |
|           | 27(4):      |              |                            |
|           | 204-211,    |              |                            |
|           | See: WHO,   |              |                            |
|           | 1996.       |              |                            |
|           |             |              |                            |
|           | **Open      |              |                            |
|           | L           |              |                            |
|           | iterature** |              |                            |
+-----------+-------------+--------------+----------------------------+
| 870.5300  | Inoue, K.   | Sodium       | At 62.5 ug/ml: induced     |
|           | et al.      | alkylbenz    | cell mutation, no effect   |
| In Vitro  | (1977)      | enesulfonate | on sister chromatid        |
| mammalian | Os          | was added to | exchange                   |
| cell gene | aka-furitsu | culture at   |                            |
| mutation  | Koshu Eisei | 62.5 ug/ml   | At 125 ug/ml: destroyed    |
| test      | Kenkyusho   | and 125 ug/l | the cells completely       |
|           | Kenkyu      |              |                            |
|           | Hokoku,     | Hamster Lung |                            |
|           | Shokuhin    | Cell         |                            |
|           | Eisei Hen   |              |                            |
|           | 8: 25-8.    | Purity: Not  |                            |
|           | (HERA)      | Reported     |                            |
|           |             |              |                            |
|           | **Open      |              |                            |
|           | L           |              |                            |
|           | iterature** |              |                            |
+-----------+-------------+--------------+----------------------------+
| 870.5300  | ## MRID No  | Duplicate    | SDDBS was negative for     |
|           | . 43498427  | primary      | transformation up to       |
| In Vitro  |             | cultures of  | cytotoxic levels and did   |
| cell      | K. Inoue et | embryonic    | not induce mutation in     |
| trans     | al (1980)   | SHE and      | either strains of          |
| formation |             | Salmonella   | Salmonalla when allplied   |
|           | Food        | typhimurium  | up to cytotoxic levels or  |
|           | Cosmetic    | strain TA 98 | limit concentration of     |
|           | Toxicol.    | and TA 100   | 2000-3000 ug/plate.        |
|           |             | cells were   |                            |
|           | 18:289-296  | exposed to   | SDDBS was tested negative  |
|           |             | SDDBS and    | at cytotoxic levels or     |
|           | ##          | positive and | limit concentrations (both |
|           |  Acceptable | negative     | with and without S-9       |
|           |             | controls for | metabolic activation) of   |
|           | **Open      | 8 days.      | 2,000-30,000 ug/plate for  |
|           | Li          |              | 2 days (Salmonella) or 8   |
|           | terature,** |              | days (SHE)                 |
+-----------+-------------+--------------+----------------------------+
| 870.5385  | Inoue K, et | LAS was      | There was no significant   |
|           | al. (1979)  | administered | difference in the          |
| Mammalian | In vivo     | at doses of  | incidence of chromosomal   |
| bone      | Cytogenetic | 200, 400,    | aberrations between any of |
| marrow    | Tests of    | and 800      | the groups                 |
| c         | Some        | mg/kg bw/d   |                            |
| homosomal | Synthetic   | by gavage    |                            |
| a         | Detergents  | for 1 and 5  |                            |
| berration | in Mice,    | days         |                            |
| test      | Ann. Rep.   |              |                            |
|           | Osaka       | M Mouse      |                            |
|           | Perfect.    |              |                            |
|           | Inst.       | Purity: Not  |                            |
|           | Public      | Reported     |                            |
|           | Health 8:   |              |                            |
|           | 17-24 (in   |              |                            |
|           | Japanese),  |              |                            |
|           | See: IPCS,  |              |                            |
|           | 1996.       |              |                            |
|           | (HERA)      |              |                            |
|           |             |              |                            |
|           | **Open      |              |                            |
|           | L           |              |                            |
|           | iterature** |              |                            |
+-----------+-------------+--------------+----------------------------+
| 870.5385  | Inoue, K.   | LAS was      | There was no significant   |
|           | et al.      | administered | difference between any of  |
| Mammalian | (1977) In   | at a dose of | the groups given LAS and   |
| bone      | Vivo        | 200, 400,    | the negative control group |
| marrow    | Cytogenetic | and 800      | in the incidence of        |
| c         | Tests of    | mg/kg bw/d   | chromosomal aberrations    |
| homosomal | Some        | by gavage    |                            |
| a         | Synthetic   | for 5 days.  |                            |
| berration | Detergents  | One          |                            |
| test      | in Mice.    | commercial   |                            |
|           | Ann Rep     | preparation  |                            |
|           | Osaka       | containing   |                            |
|           | Prefect     | 19.0% LAS    |                            |
|           | Inst Public | was also     |                            |
|           | Health, 8:  | given, at a  |                            |
|           | 17-24.      | dose of 800, |                            |
|           | (HERA)      | 1600, or     |                            |
|           |             | 3200 mg/kg   |                            |
|           | **Open      | bw, and      |                            |
|           | L           | another      |                            |
|           | iterature** | 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     |                            |
+-----------+-------------+--------------+----------------------------+
| 870.5385  | **MRID      | SDDBS was    | All test preparations were |
|           | 43498428**  | administered | negative for increased     |
| Mammalian |             | in the diet  | chromosomal damage over    |
| bone      | J. Hope     | for 90 days  | controls.                  |
| marrow    | (1977)      | at 0, 280,   |                            |
| c         | Absence of  | and 565      |                            |
| homosomal | Chromosome  | mg/kg bw/d   |                            |
| a         | Damage in   |              |                            |
| berration | the Bone    | Col          |                            |
| test      | Marrow of   | worth/Wistar |                            |
|           | Rats Fed    | Weanling Rat |                            |
|           | Detergent   | (6/sex/dose) |                            |
|           | Actives for |              |                            |
|           | 90 Days.    | Purity: Not  |                            |
|           | Mutation    | Reported     |                            |
|           | Research,   |              |                            |
|           | 56: 47-50.  |              |                            |
|           |             |              |                            |
|           | **A         |              |                            |
|           | cceptable** |              |                            |
|           |             |              |                            |
|           | Guideline   |              |                            |
+-----------+-------------+--------------+----------------------------+
| 870.5385  | Masabuchi   | LAS was      | There were no significant  |
|           | et al.      | administered | differences in the         |
| Mammalian | (1976)      | in the diet  | incidences of chromosomal  |
| bone      | Cytogenetic | for 9 months | aberrations between the    |
| marrow    | Studies and | at a dose of | experimental and control   |
| c         | Dominant    | 0.9% in rats | groups                     |
| homosomal | Lethal      | (450 mg/kg   |                            |
| a         | Tests with  | bw/d) and in |                            |
| berration | Long Term   | mice (1170   |                            |
| test      | Adm         | mg/kg bw/d)  |                            |
|           | inistration |              |                            |
|           | of          | Male Rat and |                            |
|           | Butylated   | Male Mouse   |                            |
|           | Hyd         |              |                            |
|           | roxytoluene | Purity: Not  |                            |
|           | (BHT) and   | Reported     |                            |
|           | LAS in Mice |              |                            |
|           | and Rats,   |              |                            |
|           | Ann. Rep.   |              |                            |
|           | Tokyo       |              |                            |
|           | Metrop.     |              |                            |
|           | Res. Lab.   |              |                            |
|           | Public      |              |                            |
|           | Health      |              |                            |
|           | 27(2):      |              |                            |
|           | 100-104.    |              |                            |
|           | (HERA)      |              |                            |
|           |             |              |                            |
|           | **Open      |              |                            |
|           | L           |              |                            |
|           | iterature** |              |                            |
+-----------+-------------+--------------+----------------------------+
| 870.5395  | Kishi et    | LAS was      | There were no differences  |
|           | al. (1984)  | administered | in the incidences of       |
| Mammalian | Effects of  | as a single  | polychromatic erythrocytes |
| e         | Surfactants | int          | with micronuclei in the    |
| rthrocyte | on Bone     | raperitoneal | bone marrow cells between  |
| mic       | Marrow      | injection at | the treated group and the  |
| ronucleus | Cells,      | a dose of    | control group              |
| test      | Bull.       | 100 mg/kg bw |                            |
|           | Kanagawa    |              |                            |
|           | Public      | 3 M ddY Mice |                            |
|           | Health Lab. |              |                            |
|           | 14: 57-58.  | Purity: Not  |                            |
|           | (HERA)      | Reported     |                            |
|           |             |              |                            |
|           | **Open      |              |                            |
|           | L           |              |                            |
|           | iterature** |              |                            |
+-----------+-------------+--------------+----------------------------+
| 870.5395  | Koizumi et  | LAS were     | There was no difference    |
|           | al. (1985)  | administered | among treated groups in    |
| Mammalian | I           | as a single  | the incidence of           |
| e         | mplantation | oral dose of | polychromatic erythrocytes |
| rthrocyte | Disturbance | 2 mg to      | with micronuclei in        |
| mic       | Studies     | pregnant     | maternal bone marrow or    |
| ronucleus | with LAS in | mice on day  | fetal liver or blood. No   |
| test      | Mice, Arch. | 3 of         | mutagenetic effect was     |
|           | Environ.    | gestation.   | found in any of the        |
|           | Contam.     | On day 17 of | groups.                    |
|           | Toxicol.    | gestation,   |                            |
|           | 14: 73-81.  | each animal  |                            |
|           | (HERA)      | received a   |                            |
|           |             | subcutaneous |                            |
|           | **Open      | dose of 1,   |                            |
|           | L           | 2, or 10 mg  |                            |
|           | iterature** | and were     |                            |
|           |             | killed 24 h  |                            |
|           |             | later.       |                            |
|           |             |              |                            |
|           |             | Pregnant ICR |                            |
|           |             | Mice         |                            |
|           |             |              |                            |
|           |             | Purity: Not  |                            |
|           |             | Reported     |                            |
+-----------+-------------+--------------+----------------------------+
| 870.5450  | Masubuchi   | A diet       | There were no significant  |
|           | MA et al.   | containing   | differences in fertility,  |
| Rodent    | (1976)      | 0.6% LAS at  | mortality of ova and       |
| dominant  | Cytogenetic | 300 mg/kg    | embryos, the number of     |
| lethal    | Studies and | bw/d was     | surviving fetuses, or the  |
| assay     | Dominant    | administered | index of dominant lethal   |
|           | Lethal      | to mice for  | induction (Roehrborn)      |
|           | Tests with  | 9 months.    | between the experimental   |
|           | Long Term   | Each of the  | and control groups.        |
|           | Adm         | male mice    |                            |
|           | inistration | was then     |                            |
|           | of          | mated with   |                            |
|           | Butylated   | two female   |                            |
|           | Hyd         | mice that    |                            |
|           | roxytoluene | had not been |                            |
|           | (BHT) and   | given LAS,   |                            |
|           | Linear      | and 11 of    |                            |
|           | A           | the 14       |                            |
|           | lkylbenzene | females      |                            |
|           | Sulfonate   | became       |                            |
|           | (LAS) in    | pregnant.    |                            |
|           | Mice and    | The pregnant |                            |
|           | Rats. Ann   | mice were    |                            |
|           | Rep Tokyo   | l            |                            |
|           | Metrop Res  | aparotomized |                            |
|           | Lab Public  | on day 13 of |                            |
|           | Heath,      | gestation    |                            |
|           | 27(2):      |              |                            |
|           | 100-104.    | 7 M ICR:JCL  |                            |
|           |             | Mice         |                            |
|           | (HERA)      |              |                            |
|           |             | Purity: Not  |                            |
|           | **Open      | Reported     |                            |
|           | L           |              |                            |
|           | iterature** |              |                            |
+-----------+-------------+--------------+----------------------------+
| **Met     |             |              |                            |
| abolism** |             |              |                            |
+-----------+-------------+--------------+----------------------------+
| 870.7485  | **MRID      | Single oral  | After single 30 mg/kg      |
| General   | 43498410**  | doses of     | doses the radioactivity    |
| M         |             | C14-LAS      | was rapidly excreted,      |
| etabolism | Creswell et | (SDDBS; 25   | mostly during the first 24 |
|           | al. (1978)  | ucuries)     | hours. Feces and urine     |
|           | Toxicology  | were         | contained 23.1% and 71.2%, |
|           | Studies of  | administered | respectively, in the first |
|           | Linear      | to each      | 5 days after oral dosing.  |
|           | A           | animal,      | Plasma concentrations were |
|           | lkylbenzene | following    | comparable after the oral  |
|           | Sulfonate   | 2-3 weeks    | doses and averaged 34, 41, |
|           | (LAS) in    | between dose | and 36 u/ml, respectively. |
|           | Rhesus      | levels, at   | Peak plasma concentrations |
|           | Monkeys II. | levels of    | increased proportional to  |
|           | The         | 30, 150, and | the dose and were 0.16,    |
|           | Disposition | 300 mg/kg.   | 0.72, 1.13 u/ml,           |
|           | of C14-LAS  | Following    | respectively. In urine     |
|           | After Oral  | 2-3 weeks    | samples analyzed for       |
|           | or          | after the    | metabolites, there was no  |
|           | S           | last single  | unchanged SDDBS and the 5  |
|           | ubcutaneous | oral dose,   | metabolites detected were  |
|           | Admi        | each monkey  | polar, but were not        |
|           | nistration. | received 7   | sulphate or glucuronide    |
|           | Toxicology, | consecutive  | conjugates.                |
|           | 11: 5-17.   | daily oral   |                            |
|           |             | doses of 30  |                            |
|           | **A         | mg/kg/d of   |                            |
|           | cceptable** | C14-LAS.     |                            |
|           |             |              |                            |
|           | Guideline   | 2 M/2 F      |                            |
|           |             | Rhesus       |                            |
|           |             | Monkeys      |                            |
|           |             |              |                            |
|           |             | Purity: Not  |                            |
|           |             | Reported     |                            |
+-----------+-------------+--------------+----------------------------+
| 870.7485  | Lay JP, et  | (            | From a total uptake of     |
| General   | al. (1983)  | 14)C-labeled | 1.213 + or - 0.08          |
| M         | Toxicol.    | sodium       | mg/animal of DBS, 81.8%    |
| etabolism | Letters 17  | dodecylbenz  | was excreted during the    |
|           | (1-2):      | enesulfonate | dosing period: 52.4% in    |
|           | 187-192     | was          | feces and 29.4% in urine.  |
|           |             | administered | Low levels of              |
|           | **Open      | daily in the | (14)C-DBS-derived residues |
|           | L           | diet at a    | were detected in all       |
|           | iterature** | c            | tissues analyzed on day 35 |
|           |             | oncentration | of the study. Following 1  |
|           |             | of 1.4 mg/kg | week on a normal diet,     |
|           |             | for 5 weeks  | only 7.8% of the nominally |
|           |             |              | stored amount of (14)C was |
|           |             | M Rat        | found in the excreta.      |
|           |             |              |                            |
|           |             | Purity: not  |                            |
|           |             | reported     |                            |
+-----------+-------------+--------------+----------------------------+
| 870.7485  | Sunakawa et | Sodium-para  | Blood levels were max at 2 |
| General   | al. (1979)  | -dodecylbenz | hr, negligible at 48 hr    |
| M         | Yakuzaigaku | enesulfonate |                            |
| etabolism | 39 (2):     |              | Excretion rate of          |
|           | 59-68       | Rat          | radioactive label was      |
|           |             |              | 99.4% after 48 hr          |
|           | **Open      | Purity: Not  |                            |
|           | L           | Reported     |                            |
|           | iterature** |              |                            |
+-----------+-------------+--------------+----------------------------+
| 870.7485  | The Royal   | (            | Rats excreted 64% and 24%  |
| General   | Society of  | 35)S-labeled | of the dose in urine and   |
| M         | Chemistry.  | sodium       | feces, respectively        |
| etabolism | (1981)      | dodecylbenz  |                            |
|           | Foreign     | enesulfonate |                            |
|           | Compound    | was          |                            |
|           | Metabolism  | administered |                            |
|           | in Mammals. | as a single  |                            |
|           | Volume 6: A | oral dose    |                            |
|           | Review of   |              |                            |
|           | the         | Rat          |                            |
|           | Literature  |              |                            |
|           | Published   | Purity: Not  |                            |
|           | during 1978 | Reported     |                            |
|           | and 1979.   |              |                            |
|           | London: The |              |                            |
|           | Royal       |              |                            |
|           | Society of  |              |                            |
|           | Chemistry,  |              |                            |
|           | p.354.      |              |                            |
|           |             |              |                            |
|           | **Open      |              |                            |
|           | L           |              |                            |
|           | iterature** |              |                            |
+-----------+-------------+--------------+----------------------------+
| 870.7485  | The Royal   | Repeated     | Radioactivity did not      |
| General   | Society of  | doses of     | accumulate in the tissues  |
| M         | Chemistry.  | (            |                            |
| etabolism | (1981)      | 14)C-labeled |                            |
|           | Foreign     | alkylbenz    |                            |
|           | Compound    | enesulfonate |                            |
|           | Metabolism  | were orally  |                            |
|           | in Mammals. | administered |                            |
|           | Volume 6: A |              |                            |
|           | Review of   | Rhesus       |                            |
|           | the         | Monkey       |                            |
|           | Literature  |              |                            |
|           | Published   | Purity: Not  |                            |
|           | during 1978 | Reported     |                            |
|           | and 1979.   |              |                            |
|           | London: The |              |                            |
|           | Royal       |              |                            |
|           | Society of  |              |                            |
|           | Chemistry,  |              |                            |
|           | p.354.      |              |                            |
+-----------+-------------+--------------+----------------------------+
| 870.7485  | **MRID      | LAS-S35 was  | The rate and distribution  |
| General   | 43498431**  | administered | of the excreted dose was   |
| M         |             | orally to    | independent of             |
| etabolism | W. Michael  | fasted rats  | concentration.             |
|           | (1968)      | at doses of  |                            |
|           | Metabolism  | 0.6, 1.2, 8, | Similar levels of          |
|           | of Linear   | and 40 mg    | radioactivity were found   |
|           | Alkylate    |              | in urine and feces and     |
|           | Sulfonate   | Charles      | within 3 days, 85.2% -     |
|           | and Alkyl   | River CD M   | 96.6% of the label was     |
|           | Benzene     | Rat          | recovered.                 |
|           | Sulfonate.  |              |                            |
|           | Toxicol.    | Purity: Not  | In the high dose rats, no  |
|           | Appl.       | Reported     | detectable radioactivity   |
|           | Pharmacol.  |              | was found in the carcasses |
|           | 12:         |              | after 3 days.              |
|           | 473-485.    |              |                            |
|           |             |              | Following methylation, one |
|           | **A         |              | urinary metabolite was     |
|           | cceptable** |              | identified as              |
|           |             |              | 4-(4\'-methylsulfophenyl)  |
|           | Guideline   |              | pentanoate. LAS-S35 in the |
|           |             |              | feces remained             |
|           |             |              | unmetabolized.             |
+-----------+-------------+--------------+----------------------------+
| **Special |             |              |                            |
| Studies** |             |              |                            |
+-----------+-------------+--------------+----------------------------+
| 870.3700a | Koizumi et  | LAS was      | LAS was not detected in    |
|           | al. (1985)  | administered | the uterus                 |
| Deve      | I           | as a single  |                            |
| lopmental | mplantation | oral dose of |                            |
| Toxicity  | Disturbance | 350 mg/kg bw |                            |
| (rodent)  | Studies     | on day 3 of  |                            |
|           | with LAS in | gestation    |                            |
|           | Mice, Arch. |              |                            |
|           | Environ.    | Pregnant ICR |                            |
|           | Contam.     | Mice         |                            |
|           | Toxicol.    |              |                            |
|           | 14: 73-81.  | Purity: Not  |                            |
|           | (HERA)      | Reported     |                            |
|           |             |              |                            |
|           | **Open      |              |                            |
|           | L           |              |                            |
|           | iterature** |              |                            |
+-----------+-------------+--------------+----------------------------+
| Other     | Inoue K, T  | LAS tested   | Negative results with and  |
|           | Sunakawa.   | in a         | without metabolic          |
|           | (1979)      | r            | activation                 |
|           | M           | ecombination |                            |
|           | utagenicity | assay at     |                            |
|           | Tests of    | co           |                            |
|           | S           | ncentrations |                            |
|           | urfactants, | up to 50     |                            |
|           | Jpn. Fragr. | ug/plate     |                            |
|           | J. 38:      |              |                            |
|           | 67-75, (in  | Bacillus     |                            |
|           | Japanese),  | subtilis     |                            |
|           | See: IPCS,  |              |                            |
|           | 1996.       | Purity:      |                            |
|           | (HERA)      | 99.5%        |                            |
|           |             |              |                            |
|           | **Open      |              |                            |
|           | L           |              |                            |
|           | iterature** |              |                            |
+-----------+-------------+--------------+----------------------------+
| Other     | Fujise, H.  | The          | The proline hydroxylase in |
|           | and Aoyama, | p            | the part of the skin       |
|           | M. (1984)   | roliferation | coated with the irritants  |
|           | Nagoya Med  | rate of the  | showed clearly higher      |
|           | J, 28       | connective   | activity than normal skin, |
|           | (3-4):      | tissue was   | although it was still      |
|           | 211-5       | examined by  | lower than the injured     |
|           |             | measuring    | skin region prepared as a  |
|           | **Open      | the activity | positive control.          |
|           | L           | of proline   |                            |
|           | iterature** | hydroxylase. |                            |
|           |             | The dorsal   |                            |
|           |             | neck skin of |                            |
|           |             | rats was     |                            |
|           |             | coated with  |                            |
|           |             | sodium       |                            |
|           |             | laurylbenz   |                            |
|           |             | enesulfonate |                            |
|           |             | for 4 days,  |                            |
|           |             | and on the   |                            |
|           |             | 5th day, the |                            |
|           |             | enzyme       |                            |
|           |             | activity in  |                            |
|           |             | the skin was |                            |
|           |             | measured.    |                            |
|           |             |              |                            |
|           |             | Rat          |                            |
|           |             |              |                            |
|           |             | Purity: Not  |                            |
|           |             | Reported     |                            |
+-----------+-------------+--------------+----------------------------+
| Other     | **MRID      | Ringer\'s    | Alkaline phosphatase was   |
|           | 43498430    | bicarbonate  | released by an increase of |
|           | and         | (containing  | 15-fold in comparison to   |
|           | 43498408**  | sodium       | Ringer\'s alone (controls  |
|           | Kimura et   | lauryl       | without added sodium       |
|           | al. (1982)  | benzene      | lauryl benzene sulfonate)  |
|           | Mechanisms  | sulfonate)   | and 3-7 times greater than |
|           | of          | at 0.5       | other surfactants tested   |
|           | Toxicities  | ml/min was   | in Ringer\'s. The authors  |
|           | of Some     | used to      | conclude that SDDBS has an |
|           | Detergents  | perfuse a 10 | exfoliative effect on the  |
|           | Added to a  | cm length of | intestinal brush border    |
|           | Diet and    | jejunal      |                            |
|           | the         | segment for  |                            |
|           | A           | 150 minutes; |                            |
|           | meliorating | equilibrated |                            |
|           | Effects of  | for 30       |                            |
|           | Dietary     | minutes and  |                            |
|           | Fiber in    | then the     |                            |
|           | the Rat. J. | perfusates   |                            |
|           | Nutrit.     | were         |                            |
|           | Science and | collected in |                            |
|           | Science and | 30 minute    |                            |
|           | Vi          | aliqouts for |                            |
|           | taminology, | 120 minutes  |                            |
|           | 28:         |              |                            |
|           | 483-489.    | M Wistar Rat |                            |
|           |             |              |                            |
|           | Kimura et   | Purity: 0.5% |                            |
|           | al. (1982)  |              |                            |
|           | Toxicity    |              |                            |
|           | for         |              |                            |
|           | Detergent   |              |                            |
|           | Feeding and |              |                            |
|           | Effect of   |              |                            |
|           | the         |              |                            |
|           | Concurrent  |              |                            |
|           | Feeding of  |              |                            |
|           | Dietary     |              |                            |
|           | Fiber in    |              |                            |
|           | the Rat.    |              |                            |
|           | Nutrition   |              |                            |
|           | Reports     |              |                            |
|           | Int         |              |                            |
|           | ernational, |              |                            |
|           | 26(2):      |              |                            |
|           | 271-279.    |              |                            |
|           |             |              |                            |
|           | **A         |              |                            |
|           | cceptable** |              |                            |
|           |             |              |                            |
|           | Guideline   |              |                            |
+-----------+-------------+--------------+----------------------------+
| Other     | Oba et al.  | Solutions of | The 50% haemolytic         |
|           | (1968)      | various      | concentration of LAS was 9 |
|           | Biochemical | co           | mg/litre                   |
|           | Studies of  | ncentrations |                            |
|           | n-a         | of LAS were  |                            |
|           | lpha-olefin | mixed with   |                            |
|           | sulfonates: | red blood    |                            |
|           | (II) Acute  | cells from   |                            |
|           | Toxicity,   | rabbits at   |                            |
|           | Skin and    | room         |                            |
|           | Eye         | temperature  |                            |
|           | Irritation, | for 3 hours  |                            |
|           | and Some    |              |                            |
|           | Other       | Rabbit Red   |                            |
|           | Ph          | Blood Cell   |                            |
|           | ysiological |              |                            |
|           | Properties. | Purity: Not  |                            |
|           | J Jpn Oil   | Reported     |                            |
|           | Chem Soc,   |              |                            |
|           | 17 (11):    |              |                            |
|           | 628-634.    |              |                            |
|           | (EHC 169)   |              |                            |
|           |             |              |                            |
|           | **Open      |              |                            |
|           | L           |              |                            |
|           | iterature** |              |                            |
+-----------+-------------+--------------+----------------------------+
| Other     | Samejima Y  | Eggs were    | Concentrations of LAS less |
|           | (1991)      | fertilized   | than 0.025%: Eggs exposed  |
|           | Effects of  | in vitro and | for 1 hr, washed, and then |
|           | Synthetic   | incubated in | cultured for 5 days        |
|           | Surfactants | culture      | developed normally to the  |
|           | and Natural | medium       | blastocyst stage           |
|           | Soap on the | containing   |                            |
|           | Development | LAS at       | Concentrations of LAS      |
|           | of Mouse    | co           | higher than 0.03%: The     |
|           | Embryos In  | ncentrations | eggs did not develop       |
|           | Vitro and   | between      | beyond the one-cell stage  |
|           | the         | 0.015 and    |                            |
|           | Fertilizing | 0.03%.       | With continuous exposure   |
|           | Capacity of |              | to LAS for five days, a    |
|           | Mouse and   | F B6C3F1     | concentration of 0.01%     |
|           | Human       | Mouse Egg    | slightly impaired          |
|           | Sperm. J    |              | development to the         |
|           | Osaka Univ  | Purity: Not  | blastocyst stage, and      |
|           | Med Sch, 3  | Reported     | 0.025% prevented           |
|           | (12):       |              | development to the         |
|           | 675-682.    |              | one-cell stage             |
|           | (EHC 169)   |              |                            |
|           |             |              |                            |
|           | **Open      |              |                            |
|           | L           |              |                            |
|           | iterature** |              |                            |
+-----------+-------------+--------------+----------------------------+
| Other     | Takahashi   | Purified LAS | Prothrombin time was       |
|           | et al.      | at various   | prolonged; the 50%         |
|           | (1974)      | co           | inhibitory concentration   |
|           | Inhibition  | ncentrations | was about 0.6 mmol/litre.  |
|           | of Thrombin | were added   | When LAS at various        |
|           | by Linear   | to 10 ul of  | concentrations were added  |
|           | A           | plasma from  | to a mixture of 1%         |
|           | lkylbenzene | rats and     | fibrinogen and thrombin,   |
|           | Sulfonate   | prothrombin  | the time of formation of a |
|           | (LAS). Ann  | time was     | mass of fibrin was         |
|           | Rep Tokyo   | determined   | prolonged by inhibition of |
|           | Metrop Res  |              | thrombin activity. The 50% |
|           | Lab Public  | M Rat        | inhibitory concentration   |
|           | Health, 25: |              | was about 0.05 mmol/litre. |
|           | 637-645.    | Purity: Not  |                            |
|           | (HERA)      | Reported     |                            |
|           |             |              |                            |
|           | **Open      |              |                            |
|           | L           |              |                            |
|           | iterature** |              |                            |
+-----------+-------------+--------------+----------------------------+
| Other     | Yanagisawa  | The          | Haemolysis occurred at     |
|           | et al.      | haemolytic   | concentrations \>= 5       |
|           | (1964)      | action of    | mg/litre.                  |
|           | Biochemical | LAS was      |                            |
|           | Studies of  | investigated |                            |
|           | Dod         | by mixing    |                            |
|           | ecylbenzene | red blood    |                            |
|           | Sulfonates; | cells from   |                            |
|           | Differences | rabbits with |                            |
|           | Between     | solutions of |                            |
|           | Soft and    | LAS at       |                            |
|           | Hard        | co           |                            |
|           | Detergents. | ncentrations |                            |
|           | Jpn. J      | of 1-1000    |                            |
|           | Public      | mg/litre at  |                            |
|           | Health,     | 38 C for 30  |                            |
|           | 11(13):     | min          |                            |
|           | 859-864.    |              |                            |
|           | (EHC 169)   | Rabbit Red   |                            |
|           |             | Blood Cell   |                            |
|           | **Open      |              |                            |
|           | L           | Purity: Not  |                            |
|           | iterature** | Reported     |                            |
+-----------+-------------+--------------+----------------------------+

9.2 Summary of Toxicological Dose and Endpoints for Linear Alkylbenzene
Sulfonates

+-------------+------------+---------------+--------------------------+
| Table 3.    |            |               |                          |
| Summary of  |            |               |                          |
| To          |            |               |                          |
| xicological |            |               |                          |
| Dose and    |            |               |                          |
| Endpoints   |            |               |                          |
| for         |            |               |                          |
| A           |            |               |                          |
| lkylbenzene |            |               |                          |
| Sulfonates  |            |               |                          |
+=============+============+===============+==========================+
| Exposure    | Dose Used  | Special FQPA  | Study and Toxicological  |
|             | in Risk    | SF\*,         | Effects                  |
| Scenario    | A          | endpoint and  |                          |
|             | ssessment, | Level of      |                          |
|             | UF         | Concern for   |                          |
|             |            | Risk          |                          |
|             |            | Assessment    |                          |
+-------------+------------+---------------+--------------------------+
| Acute       | No         |               |                          |
| Dietary     | endpoint   |               |                          |
|             | was        |               |                          |
| (All        | selected.  |               |                          |
| p           | No effects |               |                          |
| opulations) | are        |               |                          |
|             | at         |               |                          |
|             | tributable |               |                          |
|             | to a       |               |                          |
|             | single     |               |                          |
|             | dose.      |               |                          |
+-------------+------------+---------------+--------------------------+
| Chronic     | Systemic/  | FQPA SF = 1X  | Systemic/Reproductive    |
| Dietary     |            |               | LOAEL = 250 mg/kg/day    |
|             | Re         | cPAD =        | based on decreased Day   |
| (All        | productive |               | 21 female pup body       |
| p           | NOAEL= 50  | [chronic      | weight (Buehler, E. et   |
| opulations) | mg/kg/day  | RfD           | al. 1971. Tox. Appl.     |
|             |            | ]{.underline} | Pharmacol. 18:83-91)     |
|             | UF = 100   |               |                          |
|             |            | FQPA SF       | plus                     |
|             | Chronic    |               |                          |
|             | RfD =      | = 0.5         | LOAEL= 145 mg/kg/day     |
|             |            | mg/kg/day     | from 9 month drinking    |
|             | 0.5        |               | water rat study based on |
|             | mg/kg/day  |               | decreased body weight    |
|             |            |               | gain, and serum/         |
|             |            |               | biochemical and          |
|             |            |               | enzymatic changes in the |
|             |            |               | liver and kidney         |
|             |            |               | (Yoneyama et al. 1976    |
|             |            |               | Ann. Rep. Tokyo Metrop.  |
|             |            |               | Res. Lab. Public Health  |
|             |            |               | 27(2):105-112)           |
|             |            |               |                          |
|             |            |               | plus                     |
|             |            |               |                          |
|             |            |               | LOAEL= 114 mg/kg/day     |
|             |            |               | (0.2%) based on          |
|             |            |               | increased caecum weight  |
|             |            |               | and slight kidney damage |
|             |            |               | in a 6 month rat dietary |
|             |            |               | study (Yoneyama et al    |
|             |            |               | 1972 Ann. Rep. Tokyo     |
|             |            |               | Metrop. Res. Lab. Public |
|             |            |               | Health 24:409-440)       |
+-------------+------------+---------------+--------------------------+
| Short-Term  | Oral       | Residential   | Systemic/Reproductive    |
| Incidental  | NOAEL= 50  | LOC for MOE = | LOAEL = 250 mg/kg/day    |
| Oral (1-30  | mg/kg/day  | 100           | based on decreased Day   |
| days)       |            |               | 21 female pup body       |
|             |            |               | weight (Buehler, E. et   |
|             |            |               | al. 1971. Tox. Appl.     |
|             |            |               | Pharmacol. 18:83-91)     |
|             |            |               |                          |
|             |            |               | plus                     |
|             |            |               |                          |
|             |            |               | LOAEL= 145 mg/kg/day     |
|             |            |               | from 9 month drinking    |
|             |            |               | water rat study based on |
|             |            |               | decreased body weight    |
|             |            |               | gain, and serum/         |
|             |            |               | biochemical and          |
|             |            |               | enzymatic changes in the |
|             |            |               | liver and kidney         |
|             |            |               | (Yoneyama et al. 1976    |
|             |            |               | Ann. Rep. Tokyo Metrop.  |
|             |            |               | Res. Lab. Public Health  |
|             |            |               | 27(2):105-112)           |
|             |            |               |                          |
|             |            |               | plus                     |
|             |            |               |                          |
|             |            |               | LOAEL= 114 mg/kg/day     |
|             |            |               | (0.2%) based on          |
|             |            |               | increased caecum weight  |
|             |            |               | and slight kidney damage |
|             |            |               | in a 6 month rat dietary |
|             |            |               | study (Yoneyama et al    |
|             |            |               | 1972 Ann. Rep. Tokyo     |
|             |            |               | Metrop. Res. Lab. Public |
|             |            |               | Health 24:409-440)       |
+-------------+------------+---------------+--------------------------+
| Short-,     | Inhalation | Residential   | Subchronic Inhalation    |
| in          | study      | LOC for MOE = | Monkey Study             |
| termediate- | NOAEL=     | 100           |                          |
| and         | 1mg/m^3^   |               | LOAEL = 10 mg/m^3^       |
| Long-Term   | detergent  | Occupational  | detergent combined with  |
| Inhalation  | dust       | LOC for MOE = | 0.1 mg/m^3^ enzyme dust  |
| (1 to 30    | combined   | 100           | based on weight loss and |
| days, 1-6   | with up to |               | decreased weight gain    |
| months, \>6 | 0.1        |               | (W. Coates, et al 1978.  |
| months)     | mg/m^3^    |               | Tox. Appl. Pharmacol.    |
|             | enzyme     |               | [45]{.underline}:        |
|             | dust       |               | 477-496) This air        |
|             |            |               | concentration is         |
|             | Equivalent |               | equivalent to            |
|             | to         |               | approximately 1.4        |
|             | app        |               | mg/kg/day (a)            |
|             | roximately |               |                          |
|             | 0.14       |               |                          |
|             | mg/kg/day  |               |                          |
|             | (a)        |               |                          |
|             |            |               |                          |
|             | (          |               |                          |
|             | inhalation |               |                          |
|             | absorption |               |                          |
|             | rate =     |               |                          |
|             | 100%)      |               |                          |
|             |            |               |                          |
|             | purity=    |               |                          |
|             | 13% active |               |                          |
|             | ingredient |               |                          |
+-------------+------------+---------------+--------------------------+
| Dermal      | Quan       |               |                          |
| Endpoint    | tification |               |                          |
|             | of dermal  |               |                          |
|             | risk is    |               |                          |
|             | not        |               |                          |
|             | required   |               |                          |
|             | since: 1)  |               |                          |
|             | the        |               |                          |
|             | al         |               |                          |
|             | kylbenzene |               |                          |
|             | sulfonates |               |                          |
|             | are        |               |                          |
|             | s          |               |                          |
|             | urfactants |               |                          |
|             | that are   |               |                          |
|             | dermal     |               |                          |
|             | irritants  |               |                          |
|             | at         |               |                          |
|             | conc       |               |                          |
|             | entrations |               |                          |
|             | generally  |               |                          |
|             | greater    |               |                          |
|             | than 20%   |               |                          |
|             | solution   |               |                          |
|             | (WHO       |               |                          |
|             | 1996).     |               |                          |
|             | Thus,      |               |                          |
|             | dermal     |               |                          |
|             | exposure   |               |                          |
|             | would be   |               |                          |
|             | sel        |               |                          |
|             | f-limiting |               |                          |
|             | to         |               |                          |
|             | preclude   |               |                          |
|             | dermal     |               |                          |
|             | i          |               |                          |
|             | rritation. |               |                          |
|             | Most       |               |                          |
|             | pesticide  |               |                          |
|             | fo         |               |                          |
|             | rmulations |               |                          |
|             | have less  |               |                          |
|             | than 5%    |               |                          |
|             | al         |               |                          |
|             | kylbenzene |               |                          |
|             | sulfonates |               |                          |
|             | as an      |               |                          |
|             | inert      |               |                          |
|             | i          |               |                          |
|             | ngredient, |               |                          |
|             | with the   |               |                          |
|             | vast       |               |                          |
|             | majority   |               |                          |
|             | of         |               |                          |
|             | household  |               |                          |
|             | products   |               |                          |
|             | containing |               |                          |
|             | app        |               |                          |
|             | roximately |               |                          |
|             | 2%.        |               |                          |
|             | Add        |               |                          |
|             | itionally, |               |                          |
|             | the        |               |                          |
|             | r          |               |                          |
|             | equirement |               |                          |
|             | 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     |               |                          |
|             | ap         |               |                          |
|             | plications |               |                          |
|             | to rabbits |               |                          |
|             | at 200     |               |                          |
|             | mg/kg/day  |               |                          |
|             | (with an   |               |                          |
|             | end use    |               |                          |
|             | product);  |               |                          |
|             | 3) no      |               |                          |
|             | dev        |               |                          |
|             | elopmental |               |                          |
|             | toxicity   |               |                          |
|             | concerns   |               |                          |
|             | were seen  |               |                          |
|             | following  |               |                          |
|             | repeated   |               |                          |
|             | dermal     |               |                          |
|             | ap         |               |                          |
|             | plications |               |                          |
|             | to         |               |                          |
|             | pregnant   |               |                          |
|             | mice, rats |               |                          |
|             | or rabbits |               |                          |
|             | (dev       |               |                          |
|             | elopmental |               |                          |
|             | 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         |               |                          |
|             | r          |               |                          |
|             | esidential |               |                          |
|             | exposure   |               |                          |
|             | to         |               |                          |
|             | al         |               |                          |
|             | kylbenzene |               |                          |
|             | sulfonates |               |                          |
|             | as an      |               |                          |
|             | active     |               |                          |
|             | i          |               |                          |
|             | ngredient, |               |                          |
|             | however,   |               |                          |
|             | r          |               |                          |
|             | esidential |               |                          |
|             | exposure   |               |                          |
|             | from its   |               |                          |
|             | use as an  |               |                          |
|             | inert      |               |                          |
|             | ingredient |               |                          |
|             | in         |               |                          |
|             | pesticide  |               |                          |
|             | fo         |               |                          |
|             | rmulations |               |                          |
|             | is         |               |                          |
|             | expected   |               |                          |
|             | to be of   |               |                          |
|             | an         |               |                          |
|             | in         |               |                          |
|             | termittent |               |                          |
|             | nature     |               |                          |
|             | (i.e, no   |               |                          |
|             | c          |               |                          |
|             | ontinuous, |               |                          |
|             | constant   |               |                          |
|             | contact,   |               |                          |
|             | multi-day  |               |                          |
|             | exposure)  |               |                          |
|             | from       |               |                          |
|             | household  |               |                          |
|             | products.  |               |                          |
+-------------+------------+---------------+--------------------------+
| Cancer      | No         |               |                          |
| (oral,      | evidence   |               |                          |
| dermal,     | of         |               |                          |
| inhalation) | carci      |               |                          |
|             | nogenicity |               |                          |
|             | in         |               |                          |
|             | reported   |               |                          |
|             | studies in |               |                          |
|             | rats done  |               |                          |
|             | before     |               |                          |
|             | 1980 GLPs  |               |                          |
+-------------+------------+---------------+--------------------------+

UF = uncertainty factor, FQPA SF = Special FQPA safety factor, NOAEL =
no observed adverse effect level, LOAEL = lowest observed adverse effect
level, PAD = population adjusted dose (a = acute, c = chronic) RfD =
reference dose, MOE = margin of exposure, LOC = level of concern, NA =
Not Applicable

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

\(a\) Equation used to convert inhalation air concentration to a dose=
mg/L\* absorption\*respiratory volume (L/hr)\*duration (hrs) \* activity
factor / body weight. Thus, 0.001 mg/L \* 1\*67.94 L/hr (based on
default respiratory volumes for a New Zealand Rabbit which is used as a
surrogate for a cynomolgus monkey) \* 6 hrs \* 1 / 2.98 kg (body weight
for New Zealand Rabbit used as a surrogate for cynomolgus monkey, study
reports monkey body weight ranges from 1.6 to 3.7 kg).