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Administrative data

Description of key information

skin irritation (OECD 404): irritating
eye irritation (worst case assumption): highly irritating/corrosive
SCLs according to GHS:
>=10% - <20% Eye Irrit. Cat.2, R36
<10% No Classification

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
e.g. 24 h occluded exposure, 48 h scoring missing, observation period only 72 h
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
No data
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
24 h
Observation period:
72 h
Number of animals:
6
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24+72 h
Score:
2.2
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24+72 h
Score:
1.7
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

There are no reliable studies with C8-10AS Na (CAS 85338-42-7) regarding skin and eye irritation available. Therefore a read across to structurally related ASO4, i.e. C8AS Na (CAS 142-31-4) and C12AS Na (CAS 151-21-3) for skin irritation as well as C8AS Na (CAS 142-31-4), C10-16AS Na (CAS 68585-47-7) and C12-13AS K (CAS 91783-22-1) for eye irritation was performed.The possibility of a read-across to other alkyl sulfates in accordance with Regulation (EC) No 1907/2006 Annex XI 1.5. Grouping of substances and read-across approach was assessed. In Annex XI 1.5 it is given that a read-across approach is possible for substances, whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity. The AS reported within the AS category show structural similarity. The most important common structural feature of the category members is the presence of a predominantly linear aliphatic hydrocarbon chain with a polar sulfate group, neutralized with a counter ion. This structural feature confers the surfactant properties of the alkyl sulfates. The surfactant property of the members of the AS category in turn represent the predominant attribute in mediating effects on mammalian health. Therefore, the AS of the AS category have similar physico-chemical, environmental and toxicological properties, validating the read across approach within the category. The approach of grouping different AS for the evaluation of their effects on human health and the environment was also made by the OECD in the SIDS initial assessment profile [1] and by a voluntary industry programme carrying out Human and Environmental Risk Assessments (HERA [2]), further supporting the read across approach between structurally related AS. During evaluation of the human health hazards of the alkyl sulfates within the AS category it turned out that alkyl sulfates with a carbon chain length of C12 bear the most concern for potential adverse effects on human health. This trend is seen among others for the irritating properties of alkyl sulfates. Therefore a read across to C12AS is considered to be a worst case assumption for C8-10AS Na (CAS 85338-42-7). The available in vivo and in vitro studies but also studies on human volunteers investigating the irritating potency of alkyl sulfates in dependency of their carbon chain length are summarised in the discussion below.

Skin irritation

There is one relevant study for the read-across substance C12AS Na (CAS 151-21-3) available addressing skin irritation.

The key study conducted with C12AS Na (CAS 151-21-3) was performed similar to OECD Guideline 404 under occlusive conditions (Esposito, 1976). Each of six New Zealand White rabbits was exposed for 24 h to 0.5 mL of the unchanged test item and was observed for a period of 72 h for erythema and edema. The 48 reading time point was missing. The mean erythema and edema score after 24 and 72 h were 2.2 and 1.7. Both were not reversible within 72 h. When using the higher value of the 24 and 72 h reading time point as value for the 48 h value (per animal) the mean erythema and edema score of all animals were 2.4 and 2.2, respectively. Thus the test substance was classified as skin irritating Category 2 according to Regulation 1272/2008/EC and R38 according to Directive 67/548/EEC.

It can be expected from the available experimental results that alkyl sulfates with a shorter carbon chain length will be less irritating (see discussion below). That shorter chained alkyl sulfates are not corrosive has been evidenced in an available in vivo irritation study with C8AS Na (CAS 142-31-4). In the OECD guideline 404 study, C8AS Na (CAS 142-31-4) was applied to 3 New Zealand rabbits under semi-occlusive conditions for 4 h (BASF 2012). Skin reactions were scored 1, 24, 48 and 72 h. The observation period was 14 d. Clinical observations comprised of scaling to severe scaling, incrustations, eczema like lessions, bloody, yellowish incrustations, yellowish discoloration of application site and plaque like incrustations. The mean erythema score after 24, 48 and 72 h was 3 for each rabbit. The mean edema scores after 24, 48 and 72 h were 2, 3.3 and 3 for animals 1, 2 and 3, respectively. Erythema and edema were not fully reversible within 14 d. Thus the test substance was classified as skin irritating Category 2 according to Regulation 1272/2008/EC and R38 according to Directive 67/548/EEC.

Taken together, classification of C8-10AS Na (CAS 85338-42-7) as Xi, R38 and Skin Irrit. 2, H315 can be considered as worst case assumption. As the neat substance has to be classified as skin irritating, the substance will also be classified as “may cause respiratory irritation” (STOT SE3, H335 and R37, respectively) in case the substance is available as neat powder.

 

 

Eye irritation

There are several studies investigating the eye irritating potential of alkyl sulfates (AS) which have shown that AS concentrations of 10% and higher are moderately to strongly irritating to rabbit eyes and that formulations containing more than 20% AS can cause serious eye damage. Unless data are available that show absence of the irritating potential as defined by the EC criteria the classification Xi, R41 according to Directive 67/548/EEC and Eye Dam. 1, H318 according to Regulation (EC) 1272/2008 will be applied for the neat substance.

 

As corrosion and irritation depends on the concentration of the substance in a solvent, further studies with lower concentrations of the test substances were also considered to assess whether specific concentration limits can be set. For this purpose a read across to structurally related ASO4, i.e C12-13AS K (CAS 91783-22-1) and C10-16AS Na (CAS 68585-47-7)with a concentration range of 10 to 22%was performed.

 

In the study with C12-13AS K (CAS 91783-22-1, analytical purity 44%) 0.1 mL of the diluted test item (1:1 mixture with water) was applied to one eye of each of three New Zealand White rabbits according to OECD guideline 405 (Braun, 1978) without rinsing. In a second experiment with additional 3 rabbits the procedure was repeated but the treated eye was rinsed with 20 mL of lukewarm tap water 4 seconds after application of the test item. The eye reactions were recorded 1, 24, 48, 72 h and 4, 7, 14, 21 and 28 days in both experiments. The mean (24, 48 and 72 h reading) cornea, iris, conjunctivae and chemosis scores of experiment 1 were 2, 0.8, 2.1 and 1.7. The findings reversed in 2/3 animals within 14 days while 1/3 animals showed signs of irritation after 21 days. However, the signs of irritation show a clear tendency to decrease with time. No reading on day 28 was possible. Findings in the experiment with rinsing of the eye were less pronounced but irritating properties were also observed. As the ocular findings clearly reversed within 21 days the result of the study indicate the concentration of 22% to be the turning point between classification as severe damage to the eye and reversible eye damaging.

The first study with 0.1 mL undiluted C10-16AS Na (CAS 68585-47-7, analytical purity 10%) was performed similar to OECD guideline 405 (Kukulinski, 1980) on three New Zealand White rabbits with an observation period of 7 days. The mean (24, 48 and 72 h reading) cornea, iris, conjunctivae and chemosis scores over all animals were 1.4, 0.7, 2 and 1.6. Corneal opacity was still observed in 1/3 animals (scored 1) and conjunctival redness was still present in 2/3 animals (both scored 1) upon reading at day 7. Depending on the classification requirements the test substance is not or only moderate irritating to the eye at a concentration of 10%.

The second study with C10-16AS Na (CAS 68585-47-7, analytical purity 10%)was performed similar to OECD guideline 405(Kukulinski, 1980).0.1 mL of the undiluted test item was instilled into one eye of each of three New Zealand White rabbits. Eye reactions were scored at least 24, 48 and 72 h and 14 days after application of the test item. The mean (24, 48 and 72 h reading) cornea, iris, conjunctivae and chemosis scores were 0.9, 0.7, 1.9 and 1.6. All findings were fully reversible within the observation period. Thus, the test substance showed no eye irritating properties at a concentration of 10%.

Based on the above mentioned results with different concentrations of structurally related alkyl sulfates a cut off value for classification as severe irritating to eyes is set at a concentration of 20% and for classification as irritating at a concentration of 10%.

 

Influence of carbon chain length on the irritating properties of alkyl sulfates

In the following studies evaluating the influence of carbon chain length of alkyl sulfates on their irritating properties are summarised (for study summaries see IUCLID chapter 7.12 Additional toxicological information)

In an in vivo study with guinea pigs the dorsal skin was washed with 25 mM aqueous solutions of sodium alkyl sulfates with C9 - C15 chain lengths in a washing simulator. After washing, the wash liquors were analysed for soluble protein (Folin-Ciocalteu method) and total amino acids (spectrocolorimetric assay). The C12 alkyl sulphate was the most effective to remove soluble proteins and amino acids from the skin.

In addition to this in vivo study on guinea pigs there are three studies conducted on the skin of human volunteers available. The skin irritating effects of sodium alkyl sulfates of carbon chain lengths from C8 to C16 was assessed after application to the backs of 10 human volunteers in the scapular region (Kligman, 1967). The skin was exposed to a series of five concentrations under occlusive conditions and after 24 hours for each compound. The percentage of volunteers exhibiting a discernible erythema was determined. The percentage of volunteers showing erythema was plotted against the log of applied concentrations. The ID50 (concentration producing erythema in 50% of the volunteers) was calculated from the graph. ID50 values plotted against the carbon chain length of tested alkyl sulphate showed a maximum of irritancy at C12 followed by C10, C14, C16 and C8.

A further study with human volunteers assessing skin irritancy as a function of varying carbon chain lengths ranging from C8 to C18 was performed with sodium alkyl sulfates (Schulz, 1957). The skin of the inner forearms of 20-25 volunteers was exposed to 0.1% and 0.25% aqueous solutions of alkyl sulfate for 22-24 h under occlusive conditions and the number of volunteers exhibiting skin reactions was recorded. Irritating effects were observed in 17/25 human volunteers for C12, 10/25 human volunteers for C10, 10/25 human volunteers for C14 and 3/25 human volunteers for C8 chained alkyl sulfates. The alkyl sulfates of chain lengths C16 and C18 gave no reactions on any volunteer.

Another available study with human volunteers measured the transepidermal water loss (TEWL) and occurrence of erythema after application of sodium alkyl sulfates with variable carbon chain length from C8 to C16 (purity >99%; Wilhelm, 1993). 20 mM aqueous solutions of alkyl sulfates of varying chain lengths were applied for 24 hours under occlusive conditions to the volar forearm of volunteers. TEWL was measured with an evaporation meter and erythema was objectively quantitated by skin colour reflectance measurements with a chromameter. Increasing barrier damage (TEWL increase) and increasing erythema were observed with increasing alkyl chain length with maximum effects at C12.

The results of the human volunteer studies were confirmed by the results of two in vitro studies. The swelling of excised abdominal human skin discs in the presence of sodium alkyl sulfates at different concentrations was investigated by Choman (1961). Alkyl chain lengths from C8 to C18 (>99% purity) were used. Each skin disc was placed individually in a screw cap test tube containing 20 ml solution and was fully submerged. The discs were removed and thickness was assessed with a micrometre dial gauge. Change in thickness was calculated in terms of percentage difference between initial thickness and thickness following treatment. By plotting the percentage swelling versus log concentration, a straight line was observed. When the slopes of the swelling curves were plotted as a function of carbon chain length of each tested compound the greatest swelling response was observed for the C12 alkyl sulfate. Carbon chain lengths of C10 and C14 produced a lower swelling response followed by C8, C16 and C18.

In a second in vitro study discs of membrane tissue were set up in glass diffusion cells filled with 5 mM solutions of alkyl sulfates of various chain lengths from C8 to C16. Epidermal electrical conductance was measured by means of stainless steel electrodes (Dugard, 1973). A clear correlation between alkyl chain length and the rate of change of electrical conductance was established with a maximum at C12. This change in electrical conductance decreased from C14 to C16 and was absent at C8.

The same trend in the irritating properties of various carbon chain lengths was also observed in a study performed on rabbit eyes. In this in vivo study the effect of a series of sodium alkyl sulfates of chain lengths C8 to C18 on the conjunctivae of rabbit eyes was assessed according to Draize (Daweke, 1959).Upon instillation of 0.1 mL aqueous solutions into the conjunctival sac of the rabbit eye effects were recorded at regular time intervals and the mean Draize score of 18 parallel experiments was determined. Both at equimolar concentrations (86.5 mM) and 2.5% w/w a maximum of irritancy was observed for C12 alkyl sulfate.

 

[1] SIDS initial assessment profile, (2007);
http://www.aciscience.org/docs/Alkyl_Sulfates_Final_SIAP.pdf

[2] (HERA Draft report, 2002);
http://www.heraproject.com/files/3-HH-04-%20HERA%20AS%20HH%20web%20wd.pdf


Justification for selection of skin irritation / corrosion endpoint:
Worst case for assessment of irritation.

Justification for selection of eye irritation endpoint:
Worst case was assumed.

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: corrosive

Justification for classification or non-classification

According to the classification criteria of Directive 67/548/EEC and Regulation (EC) No 1272/2008 the test substance needs to be classified with Xi, R38/R41 and Skin Irrit. 2, H315 and Eye Dam.1, H318, respectively.

It could be shown with experimental data on eye irritation that at 10 to 20% active substance only the classification Eye Irritating Category 2 according to Regulation (EC) No 1272/2008 and according to Directive 67/548/EEC only the classification R36 remains. Below 10% active substance no classification at all is necessary. Hence, the Generic Concentration Limits (GCLs) can be substituted by the mentioned specific ones (SCLs).