JOURNALOF THE AMERICAN COLLEGE OF TOXICOLOGY

Volume 2, Number 5,1983

Mary Ann Liebert, Inc., Publishers

Final Report on the

Safety Assessment of Sodium
Laureth Sulfate and Ammonium
Laureth Sulfate

Sodium Laureth Sulfate and Ammonium Laureth Sulfate are used in cosmetic
products as cleansing agents, emulsifiers, stabilizers, and solubilizers. The in-
gredients have been shown to produce eye and/or skin irritation in experimen-
tal animals and in some human test subjects; irritation may occur in some users
of cosmetic formulations containing the ingredients under consideration, The
irritant effects are similar to those produced by other detergents, and the
severity of the irritation appears to increase directly with concentration, How-
ever, Sodium and Ammonium Laureth Sulfate have not evoked adverse re-
sponses in any other toxicological testing. On the basis of available informa-
tion, the Panel concludes that Sodium Laureth Sulfate and Ammonium Laureth
Sulfate are safe as presently used in cosmetic products.

CHEMICAL AND PHYSICAL PROPERTIES

S odium Laureth Sulfate and Ammonium Laureth Sulfate are salts of sulfated
ethoxylated lauryl alcohol. The Laureths, the conventional name for the
ethoxylated form of lauryl alcohol, are poly-ethoxyethers (polyethylene glycol
ethers) of lauryl alcohol that have the general formula CH3(CHz)loCHz-(OCHz-
CH2),0H, where "n" is the average number of ethylene oxide (EO) moieties.'')
The terminal O H groups can be sulfated and then neutralized with either NaOH
or NH40H.(z,3J Laureths 1, 2, 3, and 4 are mixtures of EO adducts of higher or
lower "n" values. Accordingly, Sodium (Ammonium) Laureth Sulfate 1 through 4
will be referred to as Sodium (Ammonium) Laureth Sulfate.

1
2 COSMETIC INGREDIENT REVIEW

Production
Production of Sodium and Ammoniuy Laureth Sulfate involves three major
steps:
1. Ethoxylation of lauryl alcohol with "n" moles of ethylene oxide,
C12H150H + (CHzCHzO)"n" Catalyst C1zHz50(CH2CH20)"n"H
"n" = 1?12 depending on the molar ratio of ethylene oxide to lauryl
alcohol in the particular ingredient.
2. Sulfation of the product with sulfur trioxide (SO,) or chlorosulfonic acid
(CISQ HI,
CI,H ZSO(CH
zCHD)nH Cl~H~50(CHzCHz),SO~H
3. Neutralization to form either the sodium ay thF ammonium salt,
OH- C12Hz50(CHzCHz0)nS03Na
C~~HZ~O(CH~CHZO),SOJH
Cation+
or S03NH4.
The complete mechanism for producing this class of compounds has been
described previously.'')

Structure and Synonyms

The structure and other chemical names for each ingredient under review
are as
1. Sodium Laureth Sulfate, CAS vumber 1335-72-4
C12HzsO(CHzCHzO)nS03Na
where n has an average value between 1 and 4.
Other names:
Sodium Dodecyl Polyoxyethylene Sulfate
Sodium Lauryl Ether Sulfate
Sodium Lauryl Ethoxysulfate
Sodium Polyoxyethylene Lauryl Sulfate
2 . Ammonium Laureth Sulfate, RD Number 977052-96-2
CizHirO(CHzCH20)nS03N
H4
where n has an average value between 1 and 4.
Other names:
Ammonium Lauryl Ether Sulfate

Properties'
In general, Sodium and Ammonium Laureth Sulfate are free-flowing, clear
liquids whose viscosity varies from a few hundred to several thousand
centip~ises.'~) Sodium Laureth Sulfate is a clear, yellow, viscous liquid with a
ASSESSMENT: SODIUM LAURETH SULFATE AND AMMONIUM LAURETH SULFATE 3

characteristic odor; it is soluble in water and alcohol. Ammonium Laureth Sulfate

is a pale, clear, yellow liquid with a characteristic odor. It is soluble in water but
generally insoluble in oils, fats, and waxes. The physical characteristics of the in-
gredients are given in Table l . ( 6 s 7 )

Micellar Properties
The critical micelle concentration (CMC) i s that point at which a surfactant
solute ceases to be in a dispersed state and instead has an equilibrium between
molecules (or ions) and aggregates (micelles).(*) Surface tension and other prop-
erties of a surfactant may change abruptly at the CMC. When, as in Sodium and
Ammonium Laureth Sulfate, a polar oxyethylene group (EO) is introduced into a
straight chain ionic surfactant molecule, the material's solubility and detergency
characteristics increase; however, as these same polar EO groups are introduced,
the CMC decreases. The extent to which this occurs depends on the position and
number of €0units introduced. WeiI et al.c9) showed that CMC values decreased
in Sodium-n-alkyl ether alcohol sulfates when the hydrophobic group chain
length increased and the hydrophilic group chain length remained constant.
The "Effective Chain Length" concept was developed to describe the changes
in surfactant properties caused by the addition of EO groups to a molecule. Effec-
tive chain length can be used to describe the relationship between CMC and
hydrophile-lipophile balance (HLB). According to the HLB, a molecule of any
surface active agent contains both hydrophobic and hydrophilic groups. Lin and
Marszall('O) have characterized this relationship with their hydrophobicity index
(HI), the ratio of the effective numbers of -CH2- groups in a chain to the actual
number in it. On the basis of the effective chain length, together with the defini-
tion of HI, values of HI that are greater than one owing to the addition of EO
groups indicate an increase in hydrophilic character of surfactants. This is the
case up to the point at which the number of EO units, with their hydrophilic
forces, balance the hydrophobic hydrocarbon chain forces. As the length of the
EO chain increases, the HI value decreases.('0)

Analytical Methods
Reverse-phasethin-layer chromatography can be used to separate a homolo-
gous series of ethoxylated alkyl sulfate surfactants. The best separations were ob-,

TABLE 1. Physical Characteristics.a

Approx. Approx.
Approx. Krafft pH of 70% Approx. Approx.
Approx. melting point aqueous cloud viscosity
M.W. point, O C I% OCb solution point at 25OC

Sodium Laureth Sulfate 420 126-136 <O 7.5-9.0 0°C max 2500 cps max
Ammonium Laureth Sulfate 400 - C
- 6.0-7.0 0-4OC -
aData from Refs. 6 and 7.
bTemperatureat which 1 % solution becomes clear on gradual heating.
CNotavailable.
4 COSMETIC INGREDIENT REVIEW

tained with glass plates covered with a 250 )tm layer of Alumina H, Alumina G, or
Silica Gel G impregnated with a 3%-5% (vlv) solution of n-dodecanol in ethanol.
The use of Pinacryptol yellow (O.0S0/0 w/v in water) with an ultraviolet viewing
chamber was found to be a satisfactory spot detection procedure. Sodium Lau-
reth Sulfate appears as a spot of blue color.(”)
Alkyl sulfates may be determined by cationic titration and by the p-Toluidine
Hydrochloride method.(’*’)
The amount of unsulfated material from the alkyl sulfates may be determined
by extraction with carbon tetrachloride from an alcohol-water solution; once
this is accomplished, the carbon tetrachloride is evaporated and the residue
weighed. Petroleum ether determination also detects unsulfated material.(’,3)
The inorganic sulfate in surfactant solutions cam be determined with a po-
tentiometric lead nitrate titration. During this process, the potential remains nearly
constant as long as the ratio of ferri-ferro cyanide does not change. When the
sulfate has been consumed, the excess titrant precipitates lead ferrocyanide, and
the potential is changed to indicate the end
Environmental levels of anionic alcohol ethoxy sulfates (AES) may be deter-
mined by the azure A colorimetric process and the two-phase titration method.
The amount of sulfate ion formed during biodegradation of surface active organic
sulfate can be measured either colorimetrically or turbidimetrically.(12)
Thin-layer, paper, and gas chromatography, as well as IR and UV spectro-
scopic methods, are used to conduct analyses for the anionic AES group.(’’)

Impurities, Diluents, Additives

The impurities, diluents, and additives of Sodium and Ammonium Laureth
Sulfate are listed in Table 2.(2*3)
Data were not available on the possible presence
of traces of ethylene glycol or 1,Cdioxane. Formaldehyde may be present as a
preservative in both Sodium and Ammonium Laureth Sulfate. Formaldehyde, in
concentrations of 2% and above, is a sensitizer according to the North American

TABLE 2. Impurities, Diluents, Additives.’

Sodium Laureth Conc. (%) Ammonium Laureth Conc. (%)
Compound Sulfate max. Sulfate max.

Impurities Sodium chloride 3 Ammonium chloride 2

Sodium sulfate 2 Ammonium sulfate 2
Unsulfated alcohol 3 Unsulfated alcohol 4

Diluents Water -b Water

Ethanol 14 Ethanol
Additives Sodium - Ammonium citrate -
bicarbonate
Sodium citrate - Formaldehyde -
Formaldehyde -
aData from Refs. 2 and 3.
bNot available.
ASSESSMENT: SODIUM LAURETH SULFATE AND AMMONIUM UURETH SULFATE 5

Contact Derhatitis Group.(") A preliminary report of a long-term study stated

that inhalation of formaldehyde at the 15 ppm level for 15 months induced
squamous cell carcinomas of the rat nasal cavity."') Concentrations at this level
would be extremely irritating to humans; occupational exposure concentrations
shall not exceed 1.2 mglm3 air (1 ppm) for any 30-minute sampling period.'l5)

USE

The US. International Trade Commission has reported that approximately 10

million pounds of ethoxylated sulfated salts of lauryl alcohol were produced in
1 973.(16'

Noncosmetic Uses
The anionic AES groups are used in light-duty dishwashing detergents.(12)

Cosmetic Uses
The laureth sulfates are used as shampoo, bath, and skin cleansing ingredi-
ents, primarily because of both their high degree of foaming and detergency and
their "softness" to the skin. They also function as emulsifiers, stabilizers, and per-
fume solubilizers and are compatible with nonionics, am,ides, amphoterics, and
other anionic systems. Their surface-active characteristics allow the laureth
sulfates to be especially useful ingredients in products that require hard water
tolerance and lime soap dispersing power. These last characteristics increase
with the degree of ethoxylation. The laureth sulfates also have a low cloud
point. (5,12.17)

Scope and Extent of Use in Cosmetics

The August 31, 1976,Food and Drug Administration (FDA) voluntary submis-
sion of cosmetic formulation data lists Sodium and Ammonium Lalrreth Sulfates
as having 298 and 63 uses, respectively."') (See Table 3.) The FDA reported in
1979 that these ingredients were used in 209 and 90 formulations, respec-
tively.(19)
The laureth sulfates are used primarily in hair care and bath preparations, in
concentrations ranging from < 1 O/O to > 50°h.(18)

Surfaces, Frequency, and Duration of Application

Products containing Sodium and Ammonium Laureth Sulfates (Table 3) are
used on all body surfaces and around all body orifices. Sodium and Ammonium
Laureth Sulfates may be applied to the body as often as several times a day (in
bath soaps and detergents) or as infrequently as once each month Or two (in hair-
coloring preparations). The duration of these applications may vary according to
use, and occasional or daily use may extend over a period of years.
TABLE 3. Product Formulation Data.”
No. product formulations within each concentration range (Vb
Total no.
containing Unreported
Product categoryb ingredient concentration >50 >25-50 > 10-25 >5-10 > 1-5 >O. 1-1 SO. 1

Sodium Laureth Sulfate

Other baby products 2 2
Bath oils, tablets, and salts 11 -
Bubble baths 59 16
Other bath preparations 78 24
Eye makeup remover 1 -
Permanent waves 13 1
Hair rinses (noncoloring) 1 -
Hair shampoos
(noncoloring) 89 8 16 19 13 -
Hair dyes and colors (all
types requiring caution
statement and patch test) 2 2 n
Hair bleaches 1 1
4 - m
Bdth-!soapsand detergents f
Other personal cleanliness
produds 2 - 2 - 2
Skin cleansing preparations
(cold creams, lotions
liquids, and pads) 19 2 1 -
Depilatories 9 2 4 1
Skin fresheners 1 - - 1

1976 TOTALS 298 - 30 49 69 71 69 6 2

1979 TOTALSC 209 - 2s 35 46 63 28 11 1

Ammonium Laureth Sulfate
Baby shampoos 1 - - - - 1 - - -
Bubble baths 6 - - 1 1 - 1 3 -
Hair rinses (noncoloring) 1 - - - - - - 1 -
Hair shampoos
(noncoloring) 23 - 1 1 1 5 14 1 -
Hair dyes and colors (all
types requiring caution
statement and patch test) 31 - - - 1 30 - - -
Bath soaps and detergents 1 - - - 1 - - - -
1976 TOTALS 63 - 1 2 rQ 36 15 5 -
6
C
1979 TOTALS 90 1 1 3 121 37 31 5 - 9I
'Data from Ref. 18.
bPreset product categories and concentration ranges in accordance with federal fling regulations (21 CFR 720.4).
CDatafrom Ref. 19.

E
x
8 COSMETIC INCRE DIENT REV1EW

BIOLOGICAL PROPE RTIE S

Sodium Laureth Sulfate

Absorption, Metabolism, and Excretion
Sodium Laureth Sulfate and other detergents are thought to modify the
physical configuration of proteins in the skin.(zo)The protein chains unfold tem-
porarily into a random, unpatterned coil rather than into the normal helix,
&sheet, or other regular conformation. In this state, the amide groups of the pep-
tide chain form hydrogen bonds with surrounding water molecules rather than
with each other. The characteristic physiochemical properties of the protein are
lost, and changes occur i n such parameters as sedimentation constant, viscosity,
and light absorption.(") There is no cleavage of the primary protein structure;
this process may therefore be reversed by the removal of the modifying agent.(21'
When the increase in sulfhydryl groups (SH) is measured, it is possible to
determine the amount of protein that unfolds. In one study, powdered human
callus exposed to 1mM (approximately 4 g percent) and 10 mM (approximately
40 g percent) concentrations of Sodium Laureth Sulfate liberated more sulfhydryl
groups than did water alone.(221In similar studies with powdered human callus,
concentrations ranging from 0.25% to 2% of Sodium Laureth Sulfate did not
liberate SH groups. Smeenk did not specify the number of ethoxy groups in the
test compound, referring to that compound simply as "Sodium salt of ethoxylate
of broadcut lauryl alcohol, anionic."("~.")
The ability of Sodium Laureth Sulfate to extract material from the stratum cor-
neum was determined through the use of the Vermeer washing simulator and
guinea pig dorsal skin. The test animal served as its own control. While the left
flank was washed with 20 ml distilled water, the right one was washed with 20 ml
of the 25 mM test solution. Following approximately five minutes of washing at
2 2 T , the wash fluid was analyzed for soluble proteins and amino acids. Sodium
Laureth Sulfate was shown to elute the proteins, whereas water alone failed to
produce such effects. Sodium Laureth Sulfate and water alone extracted the same
amounts of amino acids.(2J)
The effect of Sodium Laureth Sulfate on the permeability of human skin was
studied using the method of Bettley.(23)Two opposing perspex chambers are filled
with test solution and separated by isolated human epidermis. One chamber was
filled with a 1 % solution of Sodium Laureth Sulfate to which 10 mEq of KClll had
been added; the other was filled with distilled water. The control was distilled
water to which 10 mEq of KClll was added. The chambers were rotated in a
special apparatus at 4 rpm for one week. The quantity of potassium ions that had
diffused through the skin was used as the measure of the epidermis permeability;
this amount was determined by flame photometry. Results showed that the skin
is more permeable to K + ion transfer when it has been bathed in Sodium
Laureth Sulfate, This was consistently apparent, although the skin preparations
from different persons showed considerable differences in epidermal permeability.
There was good agreement in results obtained in duplicate experiments with
pieces of the same
The percutaneous absorption of Sodium Laureth Sulfate labeled with 14C at
the a-Carbon position of the alkyl chain was studied using the dorsal skin of four
ASSESSMENT: SODIUM LAURETH SULFATE AND AMMONIUM LAURETH SULFATE 9

live guinea pigs. The material was applied cutaneously in 0.6 ml of water (3 p o l )
to an area of 22.5 crn2on the flanks of guinea pigs. After ten minutes of rubbing,
the treated areas were washed with water and then covered with nonocclusive
patches for 24 hours. The fate of the label during the 24 hours following applica-
tion is shown in Table 4. Most of the radioactivity was found in the skin rinsings,
on the patches, or bound to the site of application. No attempt was made to
determine if the activity was in the epidermis or dermis. The level of radioactivity
in the blood was measured in samples obtained by cardiac puncture immediately
before death. No discernible radioactivity was found.(22)
Separate animals received similar doses of labeled Sodium Laureth Sulfate by
intraperitoneal (IP) injection. The proportion of the known IP dose excreted in a
given time in urine, feces, and exhaled C 0 2 was determined. To calculate the
amount of absorption through the skin, investigators divided the amount that was
excreted from the cutaneously treated animal by that excreted from the IP treated
animal. It was concluded that 2.4% of the material applied cutaneously pene-
trated the guinea pig skin during the 24-hour
Female Carworth Wistar rats were used to study the skin penetration of
Sodium Laureth Sulfate. The animals were treated with samples of the radio la-
beled compound, Sodium [1-I4C] dodecyl triethoxy sulfate, in concentrations of
0.2%- 2.0% (wlv); solutions were kept at 37OC. Aliquots of 150 or 200 pl were
dispensed from a microliter syringe onto a 10 cm2 area of the skin, which was
then covered. Expired C02, urine, and feces were collected each 24 hours for
two days, after which time the animals were sacrificed. The treated areas of skin
were excised and the carcass retained for measurement of radioactivity. Whereas
large amounts of the applied surfactant were rinsed off the skin (92.1 f 10.4%),
the treated skin retained a low proportion of the sample (5.8 f 0.9O/O), and little
*
adhered to the patch (1.2 0.2%). This evidence suggested that skin penetration
was less than 1 %. The actual amount of such penetration was determined from
the quantity of radioactivity excreted in the urine during the two days (0.39 f
0.12 pg/cm2).The penetration of Sodium Laureth Sulfate is believed to be low
because the ingredienfs ethoxylation decreases its biological activity.(26)
Other groups of rats were given the surfactant by oral intubation or by intra-
peritoneal or subcutaneous injection. The rate of excretion during the two days,
and the carcass residue were determined. When the rats were intubated or in-
jected parenterally, the urine contained a high proportion of the administered
sample. The feces and expired air contained small quantities of radioactivity.
Two days after injection, the carcass retained less than 1 O/O of the dose.(26)

TABLE 4. Distribution of Radioactivity During 24 Hours Following Application [“C]Labeled

Sodium Laureth Sulfate to the Skin of Guinea Pigs.a
Recovered radioactivity (%)

Exhaled C 0 2 Urine Feces Kidney Liver Carcass Skin at site Patch

0.6 0.5 0.3 0.0 0.95 0.0 56.9 2.0
aData from Ref. 24.
bMean of four animal assays; remaining radioactivity was recovered from the rinsings.
10 COSMETIC INGREDIENT REVIEW

The effect of Sodium Laureth Sulfate on histamine release was studied in using
the mast cells of isolated rat peritoneum.(’z) In the absence of Sodium Laureth
Sulfate there was a low level of spontaneous histamine release from the mast cells
on incubation (approx. 10% or less); however, up to 85% of total stored hista-
mine was released when the mast cells came into contact with 0.05 m M concen-
trations of the test material. This concentration was below the material’s CMC of
0.1 5-.02 mM in buffer at 22°C.(zz~z7)
Skin Swelling
When in concentrations near or above the CMC, some surfactants cause skin
to swell. Putterman et al.(ze)used Hartley guinea pig skin to study this effect.
Squares of skin 20 x 20 mm were excised, epilated, and exposed to ammonia
vapors. The separated epidermal sheets were air-dried, soaked in water for one
hour, lifted out of the water, and measured. After these sheets were immersed in
a 0.05 M solution of Sodium Laureth Sulfate (CMC = 4.8 x M ) for 16 hours,
their dimensions were again determined. Swelling is expressed in this experiment
as the percent increase in the area of a sheet, after it was exposed to the second
solution, as compared to the amount of swelling caused by the water. The level
of swelling produced by Sodium Laureth Sulfate, a hydrophilic surfactant, was
low in comparison with that produced by a purely hydrophobic, more lipid solu-
ble surfactant such as sodium lauryl sulfate. The hydrophobic chain favors
epidermal swelling.(z8)

Animal Toxicology
Acute
Oral: The acute oral toxicity of Sodium Laureth Sulfate was tested by intubat-
ing albino rats. The test methods used and the results are listed in Table 5. These
studies indicate that Sodium Laureth Sulfate is moderately to slightly toxic. At
high doses (16-64 g/kg), the toxic effects in the animals included: lethargy, di-
arrhea, rectal and nasal hemorrhage, and impaired locomotion. The animals
autopsied revealed no gross or microscopic abnormalities attributable to the test
compound. Table 5 outlines these studies.
Dermal: Sodium Laureth Sulfate was tested on the intact and abraded skin of
rabbits for dermal irritation. The results are listed in Table 6, Albino rabbits were
clipped free of hair on 10% of the toal body area; the posterior portion of the
clipped area was abraded. One 0.5 ml sample of the various compound test solu-
tions was placed over each scarified and unscarified area. These test patches
were then sealed in place with surgical tape, and the animals were immobilized
for 24 hours. After 24- and 48-hour contact periods, the skin was evaluated ac-
cording to the Draize method.*
Applications of solutions of the compound produced no irritation at
5%-5.6%. Mild erythema and edema occurred at 6%-10°/~, and at 17.5% and

*Standard Indices of Toxicity according to Draize- Primary Skin Irritation (Draize, rabbits, 8.0 max.):
0.0-no irr. potential; 0.1-0.9-potential for slight irr.; 1 .O-1 .g-potential for mild irr.; 2.0-2.9-potential for
mod. irr.; 3.0-4.9-potential for severe irr,; 5.0t -primary skin irr.; C-corrosive.
TABLE 5. Acute Oral Toxicity of Sodium Laureth Sulfate.

Effects

Test solution 10.50 valuedKg

No. dead
No. and species Conc. lest
of Rats (%) DosdKg No. dosed Solution Jngredient Comments Ref.

10 albino 5.6 5g 0110 >5 g >0.28 g No changes observed. 32

10 Wistar albino 7.5 5g 2110 >5 8 >0.38 g Nontoxic. 33
10 Wistar albino 7.5 5.0 g or
4.76 ml 0110 >5 g >0.38 g - 34
10 Wistar albino 25 5 ml 3110 > 5 ml > 1.25 ml Animals fasted 24 hours prior to treatment. 35
10 Wistar albino 25 -a - - 1.6 + 0.27 g Compound administered in a single dose. 36
Food and water ad libitum 14 days of
observation. 3 deaths on day one only.
35 albino in 26 2-64ml 21/35 13.00 ml 3.38 ml 2-4.00 mllkg-unkempt coats. 31
7 groups of 5 8.00 mllkg-diarrhea, sluggishness, unkempt
coats.
16.00-24.00 mllkg- lethargy, diarrhea, nasal
hemorrhage. *
32.00-64.00 mllkg- severe rectal hemorrhage,
z
0
lethargy, diarrhea, impaired locomotion,
nasal hemorrhage.
35 albino in 28 4-64 ml 20135 11.3 ml 3.2 ml 4.0-8.0 mllkg-lethargy, diarrhea. 31
53
7 groups of 5 10.0-12.5 ml/kg-lethargy, nasal hemorrhage, 0
diarrhea. I
C
16.00 mllkg- rectal and nasal hemorrage, 3
lethargy, diarrhea.
32.00-64.00 mllkg- severe rectal hemorrhage,
lethargy, almost comatose.
10 28 5g 0110 >5 g > 1.4 g No changes observed. 32
5 30 5g - >5 g >1.5 g Nontoxic. 37
10 Wistar albino 58 5 ml 2/10 >5 g >2.9 g - 38
Sprague-Dawley 58 - - - 1.82 g - 39
Groups of 5M and 24 - - - 2.0 g No abnormalities found. 40
5F Cartworth Food and water available ad libutum after
Farm "E" strain intubation.
d
'No data available. d
TABLE 6. Cutaneous Toxicity of Sodium Laureth Sulfate.

Jest solution No. Primary Comment

No. and days D~~of irritation No. irritated subjects
species of Route of Conc. Dose on Type of lndex
animals admin. (%) (ml) test irritation Onset Clear (PI/) No. dosed Refs.

3 albino Clipped abraded 5.0 0.5 0.0 No irritation 41

rabbits and nonabraded
skin of back
6 albino as above 5.6 0.5 3 - - 0.0 No irritation 32
rabbits
8 albino 2 in.’ patch on 6 0.5 2 Etythema 1 Application no. 1 -erythema in 5/8 42
rabbits clipped skin of Application no. 2-erythema in 7/8
back
6 albino as above 7.5 0.5 3 Slight 1 0.50 Mild transient; not a primary 33
rabbits erythema dermal irritant
6 albino Abraded and 7.5 0.5 3 Redness, 1.15 Mild transient redness and edema 34
rabbits nonabraded skin edema
of back-Oduded
patch
albino Skin of back 10 3 - 0.56 Minimal irritation 43
rabbits
rabbits as above 10 - - - 1.2 FHSLA- not an irritant 43
rabbits Skin of back 10 0.6 Not an irritant 43
rabbits Skin of back 15 3 Erythema Application no. 1 -severe erythema 29
in 116;edema in 1/6
Application no. 2 -severe erythema
in 3/6;edema in 4/6
Application no. 3 -severe erythema
in 5/6;edema in 5/6
albino as above 17.5 7 1.28 Mild irritant 30
rabbits
6 albino Abraded and 25 0.5 3 Edema, 5.3 Primary dermal irritant; edema and 34
rabbits nonabraded back- erythema erythema persisting to day 3
occluded patch
6 albino as above 25 0.5 3 Erythema, 6.13 Erythema and edema were observed 35
rabbits edema in intact and abraded skin of all
6 animals which persisted to
72 hours. Severe irritant
6 albino Clipped abraded 26 0.5 3 Very slight 1 3 0.54 FHSLA-6/6 showed mild irritation 31
rabbits and nonabraded erythema in abraded skin which cleared
skin of back- and edema within 72 hours in 316
occluded patch 0.8 DOT
6 albino Clipped abraded 26 0.5 3 0.0 FHSLA- no irritation 31
rabbits and nonabraded 0.2 DOT- mild irritation
skin of back
6 albino as above 28 0.5 3 2.04 Potential for moderate irritation 32
rabbits
3 albino Skin of back 30 3 Edema, Application no. 1 produced severe 29
rabbits erythema edema in 3/6; edema in 2/6
Application no. 3 produced severe
erythema in 5/6; edema and
cracking and drying in 2/6
6 female Topical occluded 30 0.5 3 Erythema, 1 Application no. 1 44
albino patch to clipped beet red -erythema in 5/6
rabbits skin of back reaction -severe erythema in 4/5
-beet red reaction in 1/5
rabbits Skin of back 30 7 Moderate 1 3.04 Potential for skin irritation 45
irritation
6 albino as above 58 0.5 3 0.0 Not considered a primary irritant 46
rabbits
rats Abraded and non- (0.25M) - 3 Erythema 3 - - Slight erythema and edema after 22
abraded skin of 5-10 edema 3 days application.
back-occluded
patch
~ -~ ~ ~ ~~ ~

aNo data available.

14 COSMETIC INGREDIENT REVIEW

26%. In other tests, 15%, 25%, 28%, and 30% induced severe irritation. The 15%
solution of Sodium Laureth Sulfate was also tested as described above, with one
variation: three applications of the compound were made to the rabbits' backs on
three consecutive days. After the first application, severe edema occurred in 316
and edema in 2/6; after the third, there was severe erythema in 516 and edema in
2/6 with cracking and drying.(29)Similar studies using a 17.5% solution of Sodium
Laureth Sulfate found the compound to be a mild irritant having a Primary Irrita-
tion Index (PII) of 1 ,28.(30)
Studies conducted in like manner on two 26% solutions of Sodium Laureth
Sulfate produced Plls of 0.54 and 0.0 on the Federal Hazardous Substances
Labeling Act (FHSLA) scale (ranging from 0 to 81, and 0.8 and 0.2 on the Depart-
ment of Transportation (DOT) scale. The compound produced mild irritation in
the abraded skin in 6/6 rabbits which cleared within 72 hours in 3/6.(31)
When concentration of 28% Sodium Laureth Sulfate was tested thus on six
albino rabbits, it produced moderate irritation and a PI1 of 2.04.(32)
Three different studies on 30% solutions of Sodium Laureth Sulfate were con-
ducted as described above. Three applications were made in the first of these:
application number one produced edema in 5/6 animals, and 3/6 showed severe
edema; while 5/6 exhibited severe erythema, and 216 experienced cracking and
drying after the third application.c29)The second study produced severe erythema
after the first application in 5/6 animals, and 115 showed a beet-red
The third study produced potential for severe irritation and a Pli of 3,04.(45)
An additional study conducted as above on the ingredient Sodium Laureth
Sulfate in 58% concentration produced a PI1 of 0.0 in the six rabbits tested and
cannot be considered a primary irritant.(46)
Sodium Laureth Sulfate was applied directly to the shaved dorsal skin of
weanling rats as a 0.25 M solution (representing between a 5% and 10% solution
by weight). After the first and third days of application, the degree of irritation
was assessed macroscopically in terms of erythema and edema, scaling and
cracking of the stratum corneum, and superficial drying of the stratum corneum.
Applications of water served as the experimental control. Sodium Laureth Sulfate
produced no irritation after one day's application and only very slight erythema
and edema after three days.(z2)These studies are also outlined in Table 6.
Skin Sensitization: A 0.1% aqueous solution of Sodium Laureth Sulfate was
applied topically to ten guinea pigs three times per week for three weeks. It
caused no skin sensitization when topically challenged ten days after the final
weekly application. Nevertheless, animals challenged by intradermal injections
showed a "blistering effect" one hour after the challenge. At 24 hours, there was a
"very strong positive reaction" in three animals and a positive reaction in the re-
maining seven. At 48 hours after the challenge, six animals continued to show a
definite positive reaction, and four showed a slight reaction.c1z)
Immersion Tests: The primary skin irritation potential of Sodium Laureth Sul-
fate was tested by immersion. Male or female guinea pigs with shaved bellies
were immersed in the test solution for four hours on three successive days. Skin
responses were graded daily for six days starting two days after the last treatment
(or on the fifth day of the test). The scoring system ranged from ten (normal) to
two (severe skin damage). A 0.07%~solutionof Sodium Laureth Sulfate produced
slight irritation which persisted to the sixth observation day.(47)When three 0.5%
ASSESSMENT: SODIUM LAURETH SULFATE AND AMMONIUM LAURETH SULFATE 15

concentrations of 30% Sodium Laureth Sulfate (representing a 0.15% active con-

centration of the compound) were tested, they produced minimal to no irrita-
(See Table 7.)
€ye Irritation: Ocular toxicity of Sodium Laureth Sulfate was tested by the
Standard Draize Method; 0.1 mi of the material was instilled, with or without
rinse, into the conjuctival sacs of albino rabbits, and the eyelids were momen-
tarily closed to ensure even distribution of the compound. The eyes were ob-
served for one week and were graded according to Draize scores* for corneal,
iridial, and conjunctival involvement. Any eye exhibiting corneal opacity on day
7 was considered to show a severe eye irritation. Potential corneal abnormalities
were also checked with a 2% sodium fluoroscein dye solution.
Effects ranged from no irritation to severe eye damage and were independent
of the concentration range of 1.3- 58.0 of the compound in the test solution. Test
methods used and results are compiled in Table 8.
Subcronic
Oral: Sodium Laureth Sulfate (24% wlw) was fed to two groups of six Car-
worth Farm “E” strain rats for 13 weeks. In each study, groups of 12 male and 12
female five-week-old rats were fed dietary levels of 40,200, 1000, or 5000 ppm of
the active material; control groups (1 8 males and 18 females) received a standard
diet. Daily observations were made on the health of the animals; food intake and
body weights were recorded weekly for each animal. Urine samples were col-
lected from the 5000 ppm and control groups during week 12 and were examined
for color, pH, protein, reducing substances, bile salts, and microscopic con-
stituents. Terminal blood samples were taken by cardiac puncture. Erythrocyte
and leukocyte counts and determinations of hematocrit and hemoglobin were
made, along with measurementsof total plasma protein and urea concentrations.
At autopsy, pathological examinations were undertaken. Histological examina-
tions were made of sections of a wide range of organs from animals of the 5000
ppm and control groups. Terminal body weights, food intakes, and organ
weights were statistically analyzed. The health, behavior, body weights, food in-
take, hematological results, plasma proteins, urinary findings, and urea concen-
trations were within normal limits. Rats fed 5000 ppm had increased kidney
weight in males and increased heart, liver, and kidney weights in females, but in-
creases in relative organ weights were not statistically significant.
There was no evidence of pathological changes at necropsy. Spontaneous le-
sions, mainly hydronephrosis, were present in both the control and experimental
groups of animals. The authors consider 1000 ppm as the “no-effect“ dietary level
for this test material.(401
Dermal: Rubisz-Brzezinska et al.csO)conducted a study on the effect of
anion-active detergent Sodium Laureth Sulfate on the skin and the hair cycles of
rats. The experiments were conducted on 65 seven- to eight-week-old male Wis-
tar rats weighing 60-70 g. The hair of the animals was in telogen when the ex-
periment was begun. The animals were separated into five groups: Group I
received the pure detergent (60%);group I!, 30%; group 111, 9%; group JV, 0.9%;

*Ocular Irritation (Draize, rabbits, 110 rnax.): 0.0-0.5-nonirr.; 0.5-2.5-practically nonirr.; 2.5-1 5-rnini-
mally irr.; 15-25-mildly irr.; 25-80-severely irr.; 80-1 10-extremely irr.
TABLE 7. Acute Immersion Tests."

Compound lngred. Irritation ScordDay

Sodium Laureth Species of Route of conc.
Sulfate animal administration (%I Dose 1 2 3 4 5 6 7 Comment Ref.

Raw material Guinea pig Shaved abdomens 0.07 4hr 8 8 9 9 9 9 -b Slight degree of irritation 47
as above abdomens 0.15 immersion 7 8 9 6 7 7- - - - 48
as above as above 0.15 for3days 10 8 9 6 10 - - - - - 49
as above as above 0.15 as above 8 10 10 9 10 10 - Practically no irritation

"Graded two days after last treatment: 10 = normal; 2 = severe skin damage.
bNo data available.
TABLE 8. (Continued.)

Test solution
No. and Average Score Per Day’
type Wash No. of Conc. Dose
rabbits Y/N instillations 1%) Iml) 1 2 3 4 5 6 7 10 14 Comment Ref.
albino N 1 17.5 33 24 31 27 31 Moderate eye irritant 30
3 albino N 1 20 0.1 33 32 37 32 40 Severe initial eye irritant including 57
swelling, redness, iritis, corneal
opacity, and possible permanent
eye damage
3 albino N 1 25 0.1 Each conjunctival showed intense 58
chemosis discharge and vessel
injections. Returned to normal
by 7 days.
6 albino N 25 0.1 31.2 30.5 29.7 26.3 17.7 Moderate to Severe ocular irritant 34
(M and 0
9 albino N 26 0.1 8 13.3 22.7 28 27.3 20.3 9 31
Y 2 sec 26- 0.1 4 2.6 0.6
Y 4sec 26 0.1 4.7 4 2
3 albino N 27 0.1 Cornea and irises normal. Con- 59
junctivae showed vessel .
injection, discharge, and
chemosis which cleared by
day 7.
9 New N 1 28 0.1 6.7 15.3 20.7 27.3 22.7 14.7 11.7 1’3
Zealand
albino
9 New Y 30 sec 1 28 0.1 2 0.7 0 31
Zealand Y 4sec 1 28 0.1 4 2 0
albino
6 albino N 1 28 0.1 14.7 12.0 9.3 8.3 7.5 Minimally irritating 32
albino N 1 30 0.1 25 35 37 23 16 29
albino N 1 30 31 33 36 24 15
3 albino N 1 30 0.1 24 22 20 20 13 Product at 30% induced corneal 49
Y 1 30 0.1 3 0 opacity and iritis persistent
N 1 30 0.1 21 20 21 18 13 through day 7.
Y 1 30 0.1 6 3 3 0
N 1 30 0.1 36 35 33 27 28
3 albino N 1 58 0.1 1.33 0 0 0 0 Transient, mild ocular irritant 38
ASSESSMENT: SODIUM LAURETH SULFATE AND AMMONIUM LAURETH SULFATE 19

group V, 0% (control). Tap water was used for dilution and control. The deter-
gent was applied to a 3 cmz area on the depilated backs of the animals daily for
65 days. At seven-day intervals, the condition of the skin and hair growth,
histopathological changes of the skin, and the progress of the induced and spon-
taneous hair cycles were also investigated during the 65 days of the experiment.
Daily local applications of the detergent affected the animals’ skin only in
groups I and 11. On the 12th day of the experiment, animals in group I showed
hyperkeratosis and parakeratosis, thinning of the epidermis, inflammatory re-
actions, and some of the follicles were in catagen. Seven animals in group I died
between days 13 and 15, and the remainder gained weight when application of
the detergent was discontinued for four days. On the 33rd day there was
parakeratosis, epidermal hyperplasia, acanthosis, and disappearance of the
granular layer. The inflammation of the skin persisted during the next two weeks
of applications.
Animals in group II, on 3096 Sodium Laureth Sulfate, had mild erythema after
two weeks. After 30 days, the epidermis showed epidermal hypertrophy, and the
upper part of the skin had an inflammatory reaction.
Rats in group 111 showed no changes of the skin owing to the application of
the detergent, egcept for day 65 when a mild inflammatory reaction occurred.
No changes occurred in group IV animals.
The animals in group I (6050)showed shortened anagen and premature syn-
chronized telogen in both the induced and the spontaneous hair cycle. Although
the induced cycle was normal in group II (30%) animals, the anagen phase was
shortened and premature telogen occurred in the spontaneously growing
follicles. Induced and spontaneous hair cycles were normal in rats in groups Ill
and IV.
It was concluded that the histopathological changes were similar to those
caused by certain organic solvents and that alterations of the hair cycledepended
on the concentration of the detergent. The experiments show that sodium salt of
the ethoxylated sulfate of lauryl alcohol applied to the skin of rats causes inflam-
matory changes, epidermal hyperplasia, epidermoid cyst formation, and diffuse
hair loss. A 30% solution caused similar but less severe changes; when solutions
of 9% or less were applied for two months, no changes occurred in skin or in the
hair cycle.
Chronic
Oral: Tusing et al.(391fed a diet containing Sodium Laureth Sulfate at 0.1 %,
0.5%, and 0% (control) to groups of 30 rats for 105 weeks. All three groups re-
ceived water ad libitum. At 52 weeks, ten animals of each group were sacrificed
for blood and urinelstudies and for gross and microscopic pathological evalua-
tion. Body weights and food and water consumption of individual rats were re-
corded at weekly intervals, as were observations about general appearance, con-
dition, and behavior. Rats surviving at 105 weeks were sacrificed and gross
pathology recorded. At the completion of the study, there were no differences
between experimental and control rats in appearance, behavior, organ weights,
and organ to body weight ratios. Moreover, growth rates, food consumption, and
survival of the treated and control rats did not differ markedly during the first 22
months. Male rats in the test groups had an unexplained loss of weight in the last
20 COSMETIC INGREDIENT REVIEW

eight weeks. Clinical laboratory studies at 52 and 105 weeks revealed no signifi-
cant alterations in the experimental animals as compared to the controls, Other
observations, including gross and microscopic pathology and the occurrence of
tumors, were similar in both the experimental and control groups.

Special Studies

Reproduction
Tusing et al.(3g)mated ten male and ten female rats after being fed 0.1 and
0% Sodium Laureth Sulfate for 14 weeks. The first generation offspring (FJ were
maintained on the same diets as their parents. When approximately 100 days
old, the F1 rats were bred and the F, animals were kept on the same diet for five
weeks after weaning. It was concluded that ingestion of 0.1% Sodium Laureth
Sulfate had no adverse effect on fertility, litter size, lactation, or survival of off-
spring. The material induced no changes in blood picture or urinalysis in Fl and
F2 generations, and there were no findings by gross or microscopic examination
that could be attributed to the test compound.(39)

Skin Turnorigenicity
The tumorigenicity of Sodium Laureth Sulfate was tested in groups of 30
female Swiss mice.(39)Approximately 0.1 ml of a 5% aqueous solution was ap-
plied twice weekly to the skin of the interscapular area for 105 weeks. The total
quantity of Sodium Laureth Sulfate applied to each mouse was about 1 g. Controls
had only the solvent applied. No skin tumors appeared, and mortality did not dif-
fer substantially in the two groups.

Vaginal M ucwa
Sodium Laureth Sulfate (0.28% active) was applied to the vaginal mucosa of
three dogs; no irritation had occurred 24 hours later. The undiluted material
(2890 active) produced a slight redness in two of three dogs and a diffuse tissue ir-
ritation in the third anima1.(12)
Twenty milliliters of a bubble bath formulation containing 0.07% Sodium
Laureth Sulfate were administered by intravaginal douche daily, five days a week
to three healthy, adult purebred female beagle dogs weighing between 8.2 and
9.8 kg. Three other dogs received 20 ml saline as a control.
Both before and after application, daily observations were made for signs of
systemic toxicity and vaginal irritation. Body weights were recorded weekly, and
hematology and urinalysis were determined at weeks zero and three. At the end
of the study, the dogs were sacrificed and necropsied.
The test material produced no grossly visible alterations attributable to treat-
ment. Two test animals showed a reddening of the surface of the vaginal mucosa
during the first and last weeks of treatment, but this finding was considered in-
cidental since it was observed prior to the initiation of treatment in both animals.
Hematological results, urinalysis, and pathological evaluations of vagina,
kidneys, and liver showed no changes attributable to the test material.(6o)
ASSESSMENT: SODIUM LAURETH SULFATE AND AMMONIUM LAURETH SULFATE 21

Clinical Assessment of Safety

Acute
Dermal /rritation: A %-hour occlusive patch test was used to evaluate the ir-
ritancy of a 60% aqueous solution of 30% Sodium Laureth Sulfate (18%). Three
of the 20 subjects tested showed low level irritation. The remaining 17 had no re-
action.(6')
A similar test on another 60% solution of 30% Sodium Laureth Sulfate (18%
active) produced mild irritation in 11 of the 20 subjects. The remaining nine had
no reaction.(62)
A repeat insult patch test of a dandruff shampoo containing Sodium Laureth
Sulfate was tested on 196 subjects. This shampoo containing 0.5% Sodium
Laureth Sulfate produced minimal primary irritation and no ~ensitization.'~~)
The above-mentioned Human Clinical Data studies are compiled in Table 9.
Subchronic Dermal Irritation
A 21-day cumulative irritancy assay of the Maibach type repeated insult
patch test of a shower gel formulation containing 1.25% active concentration
Sodium Laureth Sulfate was tested on 13 subjects. The compound scored 697 out
of a possible 819. It was clearly considered to be highly irritating, although spe-
cific details of the irritation produced by the ingredient were not
A 21-day cumulative patch test for the irritancy potential of a product con-
taining 14.3% Sodium Laureth Sulfate was tested on 10 subjects. A 0.5% con-
centration of the test material (0.7% Sodium Laureth Sulfate) was applied daily to
the backs of the panelists for 21 days or until a maximum irritation score was
reached. If the latter occurred, the patch was removed and the area scored for
residual irritation during the remaining scoring dates. Twenty-three hours after
the last application, the patches were removed and the areas were washed. Six
panelists withdrew from the study. The four panelists who completed the test
showed a moderate potential for mild cumulative irritation.(60)
Contact Sensitization
A maximization test to determine the contact sensitization potential of a bub-
ble bath formulation containing 14.3% Sodium Laureth Sulfate was conducted
on 25 human subjects. The material* was applied under occlusion to the same
site on the volar forearm or back of all subjects for five alternate day 48-hour
periods. The patch site was pretreated for 24 hours with 2.5% aqueous sodium
lauryl sulfate under occlusion. After a 10-day rest period, a challenge occluded
patch of the material was applied to a different site for a 48-hour period. Prior to
challenge, 5%-1O0/o sodium lauryl sulfate was applied to the test site one hour
before the test material was applied. Observations were made immediately after
the removal of the challenge patch and 24 hours thereafter. There were no in-
stances of contact sensitization from this material.(60)

*It was not stated whether or not the material was diluted. The test result reported only that the "material
was applied under occlusion."
 N
N

TABLE 9. Human Clinical Data.

Test
Sodium No. of solution
Laureth human Routeof (X) No. of reactors
Sulfate subjects admin. Active Min 0 f 1 1 + 2 2+ 3 3* 8 (Max) PI1 Comment Ref.

60% of 20 2Qhr 18 1 7 1 2 - = - - - - - - Low level of irritation 61

a 30% aq. occlusive
solution patch
20 ZQhr 18 g 2 g - - - - - - - Low level of irritation 62
occlusive
patch
Shampoo 196 0.5 Minimal primary 63
irritation
No sensitization

'No data available.

...
5
ASSESSMENT: SODIUM LAURETH SULFATE AND AMMONIUM LAURETH SULFATE 23

Photosensitivity and Contact Irritation

A sample of a bubble bath formulation containing 0.07% SodiciR Laureth
Sulfate was tested in a repeated insult patch test with ultraviolet (UV) light for
contact irritation, sensitization, and photosensitization. One-hundred and three
subjects were used. After their upper back skin was thoroughly cleansed and
dried, the product was applied under occlusion and results were read 48 hours
later. An open patch was simultaneously applied to the volar aspect of the right
wrist and read 48 hours later. Second open and closed insults were applied after
14 days and inspected 48 hours later.
The subjects' backs were exposed to an UV light source (Hanovia Tanette
Mark I Lamp with a wavelength including 3600 A) at a distance of 12 inches for
one minute. The skin sites beneath the patches were exposed and irradiated after
the second insult had been read. After 48 hours, 4 of the 103 subjects showed a
weak "nonvesicular" reaction, and all the others were negative.(60)
In a similar repeated insult photosensitivity test, a total of ten open and closed
insults of the test products were applied every Monday, Wednesday, and Friday
for three-and-a-halfweeks. After the subjects were rested for 14 days, additional
open and closed insults were applied. After 48 hours, the test areas were in-
spected and then exposed for one minute to UV light (Hanovia Tanette Mark I
Lamp) 12 inches away from the source. The skin sites under the patches were ir-
radiated after the 1st, 4th, 7th, loth, and 11th insults were read. The effect of UV
exposure on the test sites were inspected 48 hours after irradiation. Two of the 56
subjects showed a mild reaction of unspecified type, but the other panelists were
not affected. ('O)

Ammonium Laureth Sulfate

Animal Toxicology
Acute
Oral: Ammonium Laureth Sulfate solutions were tested on groups of albino
rats for acute oral toxicity. The test methods used and the results of these studies
are compiled in Table 10. Concentrations of the test compound solution ranged
from 7.5% to 27%. The LD50s of the test sohtions were found to be > 5 mllkg.
The LD5Os of the ingredient in these solutions ranged from >0.38 mllkg to > 3.3
glkg. One sample of a 12.5% concentratioti of Ammonium Laureth Sulfate caused
seven deaths in a test population of ten rats. NO other results were given. At the
27% concentration, 12 out of 50 animals died within 24 hours. The animals that
died had reddened lungs, livers, stomachs, intestines, and kidneys at the
12.1- 14.7 glkg dosage
A similar study on a 26% solution caused death in 5 out of 50 animals.(65)
(See Table 10.)
Dermal: Acute dermal irritation of Ammonium Laureth Sulfate was tested on
the clipped intact and abraded skin of albino rabbits. Concentrations of the com-
pound in the test solutions ranged from 7.5% to 6O9b. Reactions ranged from the
potential for slight irritation to severe primary irritation. Test methods used and
results of these studies are compiled in Table 11.
24 COSMETIC INGREDIENT REVIEW

TABLE 10. Acute Oral Toxicity of Ammonium Laureth Sulfate.

Effects
Test solution
LD50 ValuedKg
No. and type Conc. No. dead/
of rats (%) Dose/Kg No. dosed Test soh. Ingredient Comment Ref.

10 albino 7.5 5.0 rnl 0110 > 5 ml >0.38 rnl Not a toxic material 33
10 albino 7.5 5.0 rnl 0110 > 5 ml >0.38 ml No gross pathology seen 33
at autopsy
10 albino 7.5 5.0 ml 0110 >5 rnl >0.38 rnl No gross pathology seen 67
at autopsy
10 albino 12.5 5.0 rnl 7110 ~ 0 . 6 3 Toxic at this dosage level 68
10 albino 25 5.0 ml 0110 > 1.25 rnl -a 33
10 albino 25 5.0 rnl 0110 1.25 rnl No gross pathology seen 69
at autopsy
50 Charles River; 27 1-100 g 12/50 11.9 g,M 3.2 g,M All deaths occurred 65
Sprague-Dawley 12.3 g,F 3.3 g,F within 24 hours
50 Charles River; 26 1-100 g 5/50 6.8 g 1.7 g In both 26 and 27% 65
Sprague-Dawley solutions, all anipals
that died showed
reddened lungs, livers,
stomachs, intestines,
and kidneys at the
12.1-14.7 g/kg dosage
level.

aNo data available.

Acute Dermal LD50: A bubble bath formulation containing22% Ammonium

Laureth Sulfate was tested for acute dermal LD50 on four albino rabbits. The
backs of the rabbits were clipped of hair, and a 1O h solution (0.22% Ammonium
Laureth Sulfate) was applied in 5 glkg doses. It should be noted that the dose of
the specific ingredient was only 0.01 glkg. The sample was applied under rubber
dental dam and held in place for 24 hours. The animals were observed for 14
days, after which they were sacrificed and examined for gross pathology. None
of the animals died during the observation period, and none showed signs of in-
toxication. There were no gross pathological findings at necropsy.(66)
Acute Immersion: Ammonium Laureth Sulfate was evaluated for skin irritancy
by immersing two groups of guinea pigs in 0.06% solutions for four hours per day
for three days. The compound produced mild irrifation;("j) solutions containing
0.07% and 0.14% produced no irritation.('0)
Ocular Irritation: The acute ocular irritation of Ammonium Laureth Sulfate
was tested according to the Draize method on groups of albino rats. Concen-
trations of the test solutions ranged from 7.5% to 60% and were instilled into the
eyes, with or without wash-out, in doses of 0.1 ml. Effects ranged from transient,
mild ocular irritation to severe irritation. Test methods and results of the studies
are compiled in Table 12. (See footnote on Draize eye irritation scores.)
Vaginal Irritation: Ammonium Laureth Sulfate in a bubble bath was tested
for local vaginal irritation and systemic toxicity in beagles for three weeks. The
sample, which contained 0.1 1 concentration of the compound, was applied by
TABLE 11. Acute Dermal Irritation of Ammonium Laureth Sulfate.
~~

Test solution
No. of Day of
albino Route of Conc. No. days Type of Comment
rabbits admin. (%) Dose on test irritation Onset Clear PI1 (No.irritated SubjectdNo. dosed) Ref.

6 Clipped 7.5 1.5 3 Erythema 0.5 Potential for slight irritation; 33

1s
abraded and rarely irritating to people: slight
4!
C
nonabraded erythema at day 1 3
skin of back
6 as above 7.5 1.5 3 Erythema 0.9 Potential for slight irritation; 67
6
C
erythema at day 1 in 6/6,
persisting to day 3 on 416 EIi
6 as above 7.5 1.5 3 Erythema 3 0.7 Erythema seen at 24 hours, but 67
disappearing after 72 hours
8 as above 12 1.5 3 Erythema 618 showed definite erythema 42
after day 1; 818 after day 2
9 as above 15 1.5 3 2.00 Moderate skin irritant 70
9 as above 15 1.5 3 3.23 Moderate skin irritant 71
9 as above 15 1.5 3 3.22 Moderate skin irritant 72
z
0
6 as above 25 1.5 3 Erythema, 8.0 Severe primary irritant 73
edema
6 as above 25 1.5 3 Erythema, 5.21 Severe irritant to the skin 69
edema
6 as above 25 1.5 3 Erythema, 4.1 Potential for severe irritation 67
edema
6 Clipped 31 1.5 3 1.76 Mild irritation 74
abraded and 5
C
nonabraded
skin of back 5I
6 as above 31 1.5 3 2.1 1 Moderate skin irritation 75
(unspecified)
6 as above 31 1.5 3 1.17 Moderate skin irritation 75
(unspecified)
6 as above 61 1.5 3 Severe At least moderate to severe 42 m
erythema irritation after application in 6/6
N
01
TABLE 12. Eye Irritation of Ammonium k u r e t h Sulfate- Draize Method.a

Jest solution
No. of Average Score Per Day
albino Wash No. of Conc. Dose
rabbits Y/N instillations (%) . (mml) 7 2 3 4 5 6 7 10 74 Cornrnent Ref.

6 N 1 7.5 0.1 15.7 11.8 4.7 1.2 0 Transient mild ocular irritant 67
6 N 1 7.5 0.1 13.3 13.6 7.6 TO 10.1 Mild ocular irritant 67
6 N 1 7.5 0.1 15.5 8.5 7.3 2.1 0 Mild ocular irritant 33
6 N 1 15 0.1 32 25 33 22 16 70
15 0.1 36 15 16 11 8 77
3 N 1 20 0.1 32 26 21 12 4 Corneal opacity and iritis 44
clearing by day 7
6 N 1 25 0.1 25.1 23.3 24.7 21.5 Severe irritant to rabbit eye 69
when not followed by
washout
6 N 1 25 0.1 16.1 16.3 13 4.7 Severe transient irritant when 73
not followed by washout
3 N 1 25 0.1 17.6 17.6 21.5 22.6 Severe ocular irritant 67
3 N 1 26 0.1 16 14.3 13.7 13.7 4.6 Corneal damage, iritis, beefy 65
redness, chemosis
3 YZSec 1 26 0.1 2 1.3 1.3 0.6 0.3 Slight redness of conjunctivae 65
3 Y4sec 1 26 0.1 3.3 2 0.6 0.6 0
3 N 1 27 0.1 10.7 12.3 17.3 17.3 3 3 0.66 Corneal damage, beefy
redness, iritis, chemosis
3 YZSec 1 27 0.1 0.3 2 1.3 1.3 0 Slight redness of conjunctivae
3 Y4Sec 1 27 0.1 2 0 0.6 1.3
3 N 1 30 0.1 31 25 21 21 21 74,75,76 -
6 1 30 0.1 35 26 24 21 11 74.75,76 z
6 N 1 30 45 34 25 23 8 74,75,76 0
N 1 30 55 44 35 31 28 74'75'76
N 1 30 30 26 18 15 74,75,76 0
-
m
N 1 30 31 23 20 20 15 74,75.76
N 1 30 31 25 21 21 21 I
74.75.76.
5
3 N 1 60 0.1 38 29 27 20 14 Corneal effects and iritis 57 z-
' S e e footnote on Draize eye irritation scores. m
s
ASSESSMENT: SODIUM LAURETH SULFATE AND AMMONIUM LAURETH SULFATE 27

vaginal douche for five days a week. Three untreated dogs served as the control,
Daily observations were made for systemic toxicity and vaginal irritation, body
weights were recorded weekly, and hematology and urinalysis were determined
at weeks 0 and 3.
During the study, all dogs maintained their normal appearances and behav-
ior and gained weight. Hematology and urinalysis of treated and control dogs
were comparable. Gross pathology showed slight redness in the distal portion of
the vagina in one treated dog, and redness in proximal and distal portions of a
second one; neither appeared to be compound-related. The prdduct produced
no gross or microscopic changes in the vaginal mucosa.(66)
Su bchronic
Dermal: In a 28-day irritation study, unrestrained rabbits with abraded skin
sites were treated with aqueous solutions of "Ammonium alcohol ethoxy sulfate"
(the specific alcohol and degree of ethoxylation were not stated). The first topical
application contained 200 mg/kg of active ingredient; all applications thereafter
contained 50 mg/kg. Histological examinations revealed moderate to severe skin
inflammation. (12)

Clinical Assessment of Safety

/ I

Dermal Contact lrritationlSensitization

A bubble bath containing 23% Ammonium Laureth Sulfate was used in a
standard Repeated Insult Human Patch test on 189 subjects. A 1.25% aqueous
solution of the product (0.29% Ammonium Laureth Sulfate) was used for the in-
duction phase; the challenge concentration was 0.63% (0.15% Ammonium
Laureth Sulfate). During induction, one-third of the subjects had mild to mod-
erate irritation. When the challenge concentration was lowered to 0.63% in
order to minimize irritation responses, nine persons exhibited weak sensitization
reactions; follow-up testing did not confirm reactivity in these individuals. It was
concluded that this formulation possessed a minimal potential for inducing irri-
tant contact dermatitis.(78)These same conclusions were reached when a 0.1 15%
active solution of Ammonium Laureth Sulfate in a bubble bath was tested on 86
When 94 subjects were tested with this bubble bath at a 1o/o aqueous
solution at induction (0.234b Ammonium Laureth Sulfate) and 0.5% solution at
challenge (0.1 15% Ammonium Laureth Sulfate) the results showed a minimal
potential for irritant contact
A bubble bath formulation containing 23%Ammonium Laureth Sulfate was
tested for skin irritation on 20 human subjects. The 1.25% test concentration
(0.28% ingredient concentration) was applied under occlusion in a single insult
for 24hlours. The material produced no effect in 11 of the 20 subjects, faint uni-
form b'r spotty erythema in 4 of 20, mild, pink, uniform erythema covering most
of the contact sight in 4 of 20, and marked bright red erythema with edema,
petechiae and papules in 1 of the 20.(81)
A three-week repeated insult occluded patch test was conducted on 68 men
and women with a 0.5?0 solution of a bubble bath containing 22% Ammonium
Laureth Sulfate. (This is a 0.1 1O/O concentration of the compound in the sample.)
Patch sites were scored prior to the patch applications at the second through the
28 COSMETIC INGREDIENT REVIEW

tenth visit. Challenge sites were scored 48 and 96 hours after application. The
bubble bath sample was essentially nonirritating following initial application. Re-
peated applications of the sample produced moderate irritation in about 16% of
the panelists, but there was no indication of sensitization following the applica-
t ions. ( 6 6 )
Table 13 presents these results.
Pho totoxicity
Twenty-five men and women were used to study the phototoxic properties of
a bubble bath containing 0.1 19'0 Ammonium Laureth Sulfate. Occlusive patches
of the test material at 0.5 ml per patch were applied to the arms of the panelists at
2:OO p.m, on each of five consecutive days, and removed at 1:00 p.m. the follow-
ing day. The test sites were scored immediately after patch removal. On all ex-
cept two consecutive days, about 0.1 ml of each test material was then swabbed
into the respective test sites, and the panelists exposed the areas to direct sunlight
for 30 minutes.
Moderate skin irritation was seen on six panelists following the application of
the sample. The irritation was transitory and in several instances occurred even
when not exposed to light. The 6 of the 22 panelists who showed irritation were
believed not to have phototoxic reactions.'66)

TABLE 13. Human Clinical Data- Dermal Irritationhensitization of Ammonium Laureth Sulfate.

Test
Cosmetic No. of solution
product human Route of I%)
type subjects admin. active PI1 Comment Ref.

Bubble bath 189 Single and 0.29 at One-third of the panelists exhibited 78
repeat induction mild to moderate irritation.
insult 0.15 at Nine exhibited weak sensitization 78
occlusive challenge reactions; follow-up testing did
patches not confirm reactivity in these
individuals.
Bubble bath 86 as above 0.115 0186 sensitized; mild to moderate 79
irritation at induction; no
follow-up sensitization
Bubble bath 94 as above 0.23 at 0/94 sensitized 80
induction
0.115 at This bubble bath formulation
challenge possesses no to minimal potential
for inducing contact dermatitis.
Bubble bath 20 as above 0.28 1 1/20- no reaction 81
4/20- mild reaction
4/20-mild reaction; erythema over
most of contact site
1/20 marked erythema, edema,
papules
Bubble bath 69 as above 0.11 16% of the panelists showed 66
irritation after repeat applications.
No indication of sensitization

aNodata available.
ASSESSMENT: SODIUM LAURETH SULFATE AND AMMONIUM LAURETH SULFATE 29

Twenty-One-Day Cumdative Sensitivity Test

Two bubble bath preparations containing 0.1 1 O/O Ammonium Laureth Sulfate
were used to study sensitization potential.
Patches with test samples were applied to the back of each of 12 panelists.
Daily applications of the samples were made to the same test sites for 21 consecu-
tive days or until irritation scores of 3 or equivalent were observed. In the latter
cases, application of the sample was discontinued.
The 20-mm2squares of cotton patches were affixed to adhesive patches. Five
patches were applied to each side of the back for a total of ten per subject; these
were removed 23 hours after each daily application, and panelists were in-
structed to bathe or shower immediately after removal and to keep the areas dry
at other times. Reactions were scored 24 hours after the sample had been ap-
plied.
The material caused erythema and papules, and it was 'concluded that the
two products showed evidence of having moderate potential for mild cumulative
irritation under continued reapplication and
Ocular Irritation
Tests were performed on ammonium alcohol ethoxy sulfate (the length of
alkyl chain and degree of ethoxylation was not specified) in 10 and 20% con-
centrations of a liquid formulation containing 9% active material. This substance
was found to be nonirritating when instilled into the eyes of 20 human volun-
teers. (I2)
Mucosal Irritation
When applied once daily for two weeks to male and female genitalia, a 25%
solution of a product containing 9% "ammonium alcohol ethoxy sulfate" was
found to be nonirritating.(12)

SUMMARY

Sodium Laureth Sulfate and Ammonium Laureth Sulfate are salts of sulfated
ethoxylated lauryl alcohol, which conforms to the general formula: CH,(CH2)
loCH2-(OCH2CH2),0H, where n is the average number of ethylene oxide moi-
eties. The terminal-OH groups are sulfated and then neutralized with either
NaOH or N H 4 0 H to form the sodium or ammonium salts. The Laureth Sulfates
are clear liquids, soluble in water and alcohol. Used as shampoo, bath, and skin
cleansing ingredients, these also function as emulsifiers, stabilizers, and solubiliz-
ers. The concentration of Sodium Laureth Sulfate in cosmetics ranges from less
than or equal to 0.1% to greater than 50%, and that of Ammonium Laureth Sul-
fate ranges from greater than 0.1 O h to greater than 50%. Laureth Sulfates are re-
ported to contain unspecified amounts of formaldehyde. Formaldehyde vapor
has been shown to induce tumors in rats; according to the North American Con-
tact Dermatitis Group, formaldehyde is a skin sensitizer.
Skin bathed in Sodium Laureth Sulfate is more permeable to potassium ion
transfer but has a low-level of percutaneous absorption. Concentrations of 0.05
mM of Sodium Laureth Sulfate released up to 85% of the total stored histamine
30 COSMETIC INGREDIENT REVIEW

from isolated rat peritoneal mast cells. Since it is an hydrophilic surfactant, this salt
produced a low level of swelling when in contact with excised guinea pig stratum
corneum.
Studies have shown that Sodium Laureth Sulfate in concentrations ranging
from 5.6 to 58% is slightly toxic to rats according to the classification of Hodge
and Sterner.(8L1)
When Sodium Laureth Sulfate in concentrations of 60% and 30% was ap-
plied to the skin of rats, it produced severe epidermal irritation and impairment
of hair growth. Applications of the compound to the clipped abraded and
nonabraded dorsal skin of albino rabbits produced no irritation at concentrations
of 5%-5.6%,minimal irritation at 6%-lO%,and severe irritation at 25%. Immer-
sion of guinea pigs in a 0.1 YO solution of the compound caused no skin sensitiza-
tion and mild irritation at concentrations of 0.07%-0.19%.
in a subchronic oral toxicity study in rats, 1000 ppm of this compound in the
diet had no effect. in a chronic oral toxicity study in rats fed 1000 ppm and 5000
ppm Sodium Laureth Sulfate in the diet for 105 weeks, none of the animals showed
gross or microscopic changes. Rats eating 0.1% of the compound in the diet
showed no effects in the reproductive performances of the For Fl, or Fz genera-
tion.
The application of 5 mg of Sodium Laureth Sulfate to mice twice a week for
105 weeks produced no skin tumors.
Solutions of 0.28% Sodium Laureth Sulfate were nonirritating to the vaginal
mucosa of beagles, and a 28% solution produced redness. A formulation con-
taining a 0.07% concentration of the compound did not cause any irritation on
the vaginal mucosa of beagles when applied for three weeks.
in clinical studies, an 18%solution of the compound tested under occlusion
produced a low level of irritation in 3 of 20 subjects. Another 18% solution
brought about mil@irritation in 1 1 out of 20 subjects. No primary irritation or
sensitization was produced by a 0.5% solution of the compound in,f$rmulation
when it was tested on 196 volunteers. A subchronic dermal study fqynd a 1.25%
solution of the material to be highly irritating, while another study @,singa 0.07%
solution in formulation indicated a "moderate potential for mild cumulative irrita-
tion" in the four tested panelists. A formulation containing 14.3%Sodium Laureth
Sulfate caused no contact sensitization.
A formulation containing a 0.07% concentration of the compound, when
tested for phototoxicity, caused a "weak, nonvesicular" reaction in four of 103
panelists. A similar test produced a mild reaction of unspecified type in 2 of 56
subjects. , I - \I:'

No absorption, metabolism, and excretion studies were reported for Am-

monium Laureth Sulfate. ,
Ammonium Laureth Sulfate in concentrations ranging from 7$"/0 to 27% was
tested for acute oral toxicity in rats; the material was considered thbe slightly toxic.
Ammonium Laureth Sulfate in concentrations ranging from?.5% to 60%was
tested for dermal toxicity. At concentrations of 15% and greate!,, severe irritation
occurred and the calculated acute dermal LD50 was greate,r than 5.0 glkg.
Guinea pigs immersed for four hours per day for four days in 0.06°~-0.140/~ Am-
monium Laureth Sulfate had mild skin irritation. In ocular irritation studies, a
ASSESSMENT: SODIUM LAURETH SULFATE AND AMMONIUM LAURETH SULFATE 31

7.5% concentration produced mild irritation. Irritation increased as concen-

tration increased.
The vaginal mucosa of the beagles exposed to 0.1 1O/O solution of Ammonium
Laureth Sulfate five days a week for three weeks showed no irritation. In a sub-
chronic dermal study on rabbits, 200 mg/kg of the compound were used in the
first application and 50 mg/kg in subsequent applications; the ingredient gave rise
to moderate to severe skin irritation.
When a formulation containing 23% Ammonium Laureth Sulfate was tested
for its potential for causiog allergic reacfjpns, it was adjudged to possess a mini-
ma1 potential for contact dermatitis. The same conclusions were reached when a
9.1 15% solution in a formulation was tested on 86 subjects and a 0.23% on 94
others. A O.284b sample of the compound tested on 20 subjects showed that 1 1
were reaction-free; 8 had a mild reaction, and 1 a moderate reacFion. A formula-
tioncorkqining 0.1 1 O/O Ammonium Laureth Sulfate was used for a rFpeated insult
patch ~ s $Qni 68 subjects. The initial application produced no irritation. Repeated
appliqfion produced moderate irritation in 16%, but no sensitization occurred.
A photosensitization test of a sample containing 0.1 1 % of the compound
produced irritation in 6 of the 22 panelistq. However, the reactions probably in-
dicated primary irritation and not phototoxicity. A 21-day cumulative irritancy
test with a sarngle containipg 0.1 1 O/O of the compound produced erythema and
papules. Ten as@20% Egncentrations of a liquid containing 9% active material
were found to be nonirripting following instillation into the eyes of 20 volun-
teers. A 2.25Ok tonceptration of the compound caused no irritation when ap-
plied to malg gnd fern& genitalia once a day for !yo weeks.

DISCUSSION

Sodium Laureth Sulfate and Ammonium Laureth Sulfate are cosmetic

detergents that exert emulsifying action, thereby removing oil and soil from the
hair and skin. The Panel wishes to point out that these two ingredients produce
eye and/or skin irritation in experimental animals and in some human test sub-
jects; irritation may occur in some users of cosmetic formulations containing the
ingredients under consideration. The irritant effects are similar to those produced
by other detergents, and the severity of the irritation appears to increase directly
with concentration. However, Sodium and Ammonium Laureth Sulfate have not
evoked adverse responses in any other toxicological testing.

CONCLUSION

It is recognized that Sodium and Ammonium Laureth Sulfate may induce eye
and skin irritation. However, on the basis of available information, the Panel con-
cludes that Sodium Laureth Sulfate and Ammonium Laureth Sulfate are safe as
presently used in cosmetic products.
32 COSMETIC INGREDIENT REVIEW

ACKNOWLEDGMENT

Anne Moore, Scientific Analyst and writer, prepared the literature review
and technical analysis used by the Expert Panel in developing this report.

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ASSESSMENT: SODIUM LAURETH SULFATE AND AMMONIUM LAURETH SULFATE 33

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38. LEBERCO LABS. (July 13, 1976). Submission of data by CTFA. Acute oral toxicity with rats; Acute eye irrita-
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Laureth Sulfate.*
43. IBTL. (June 19, 1975). Submission of data by CTFA. Primary Skin Irritation: Sodium Laureth Sulfate.*
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Sulfate.*
34 COSMETIC INGREDIENT REVIEW

56. AVON. (Dec. 14, 1975). Submission of data by CTFA. Unpublished safety data on Sodium Laureth Sulfate.'
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60. CTFA. (Jan. 25, 1980). Submission of data. Unpublished safety data on Sodium Laureth Sulfate.*
61. AVON. (June 15, 1972). Submission of data by CTFA. Unpublished safety data on Sodium Laureth Sulfate.*
62. AVON. (April 16,1972). Submission of data by CTFA. Unpublished safety data on Sodium Laureth Sulfate.*
63. HILL TOP RESEARCH (HTR). (July 23, 1973.) Submission of data by CTFA. Data on Cosmetic Products.
Repeat Insult Test-Human: Sodium Laureth Sulfate.;
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Dermal Irritation: Sodium Laureth Sulfate.'
65. HAZELTON LABS. (Sept. 21, 1973). Submission of data by CTFA. Acute oral toxicity; Acute Eye Irritation:
Ammonium Laureth Sulfate.*
66. CTFA. (Jan. 25, 1980). Submission of data. Unpublished safety data on Ammonium Laureth Sulfate:
67. CPTC. (Sept. 7, 1976). Submission of data by CTFA. Unpublished safety data on Ammonium Laureth
Sulfate.*
68. FDRL. (June 1, 1976). Submission of data by CTFA. Acute oral toxicity with rats: Ammonium Laureth
Sulfate.*
69. FDRL. (Feb. 4, 1976). Submission of data by CTFA. Acute oral and dermal toxicity test with rats: Ammonium
Laureth Sulfate. *
70. AVON. (Jan. 6, 1977). Submission of data by CTFA. Unpublished safety data on Ammonium Laureth
Sulfate.*
71. AVON. (Jan. 10, 1977). Submission of data by CTFA. Unpublished safety data on Ammonium Laureth
Sulfate.*.
72. AVON. (March 15, 1977). Submission of data by CTFA. Unpublished safety data on Ammonium Laureth
Sulfate.*
73. FDRL. (May 24, 1976). Submission of data by CTFA. Primary skin irritation study with rabbits; Acute eye ir-
ritation with rabbits: Ammonium Laureth Sulfate.*
74. AVON. (June 17, 1976). Submission of data by CTFA. Unpublished safety data on Ammonium Laureth
Sulfate.*
75. AVON. (Dec. 13, 1976). Submission of data by CTFA. Unpublished safety data on Ammonium Laureth
Sulfate. *
76. AVON. (Sept. 26, 1977). Submission of data by CTFA. Unpublished safety data on Ammonium Laureth
Sulfate.;
77. AVON. (Jan. 15, 1977). Submission of data by CTFA. Unpublished safety data on Ammonium Laureth
Sulfate.'
78. HTR. (April 21, 1977). Submission of data by CTFA: Data on Cosmetic Products. Human contact Irrita-
tionlSensitization: Ammonium Laureth Sulfate.*
79. CTFA. (Aug. 25, 1977). Submission of data. Unpublished safety data on Cosmetic Products. Ammonium
Laureth Sulfate.*
80. CTFA. (Dec. 16, 1977). Submission of data. Unpublished safety data on Cosmetic Products. Ammonium
Laureth Sulfate.*
81. CTFA. (May 16, 1978). Submission of data. Unpublished safety data on Cosmetic Products. Ammonium
Laureth Sulfate.'
82. HODCE, H.C. and STERNER, J.H. (1949).Tabulation of Toxicity Classes. Am. Ind. Hyg. A. Quart. 10,93-6.