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Administrative data

Description of key information

skin irritation (OECD 404): irritating
eye irritation (OECD 405): 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

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

There are several data regarding skin irritation and eye irritation of C12-18AS Na (CAS 68955-19-1) available. However, the endpoint eye irritation is further covered by read across from structurally related alkyl sulfate (AS), i.e. C12-16AS Na (CAS 73296-89-6), C10-16AS Na (CAS 68585-47-7) and C12-13AS K (CAS 91783-22-1) to provide studies where higher concentrations of active substances were applied. 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.

Skin irritation

There is one relevant study for C12-18AS Na (CAS 68955-19-1) available addressing skin irritation.

The key study conducted with C12-18AS Na (CAS 68955-19-1, analytical purity 89%) was performed according to OECD Guideline 404 under semi-occlusive conditions (Pels Rijcken, 1994). Each of three New Zealand White rabbits was exposed for 4 h to 0.5 g of the unchanged test item and was observed for a period of 14 days for erythema and edema. The mean erythema score (24, 48 and 72 h reading) and the mean edema score were 3 and 2.3, respectively. Both effects were fully reversed within the 14 days observation period.

Further studies on the skin irritating properties of C12-18AS Na (CAS 68955-19-1) were performed with lower concentrations of the test item. Either the limited database of the study reports (Henkel 1981, rabbit) or the methods used do not allow any conclusions regarding classification purposes. Therefore only a short summary of those studies is reported in the following text.

The study conducted with C12-18AS Na (CAS 68955-19-1, analytical purity 35%) was performed at final concentrations of 10% on mice skin (Henkel, 1981). The test substance was applied twice daily for 5 days. No skin reactions were observed. In the same study report, C12-18AS Na (CAS 68955-19-1, analytical purity 35%) at a final concentration of 5% was applied as patch test for 4 h on rabbits. Only a slight and reversible skin reaction was observed. In another study, 1-2 drops of 5% C12-18AS Na (CAS 68955-19-1) were applied to the dorsal skin of 5 hairless mice (Henkel, 1985). Treatment was done once daily during days 1-4 and twice daily during days 5-13. The treatment caused no signs of irritation.

The available human study was performed on 20 healthy volunteers. 0.1 mL of a 0.5% solution of the test item was applied under occlusive conditions using the Duhring Chamber for 24 h on day one and for 6 h per day during days 2-5 (Kästner, 1981). Scoring of skin reactions was performed 3 days after the last application. The irritation score was 67 of maximum 220 and judged as strongly irritating by the authors. Also intradermal injection of 5 and 10 % aqueous solutions of C12-18AS Na (CAS 68955-19-1) to mice revealed skin irritation judged as strongly irritating by the authors (Kästner, 1981b).

Eye irritation

In one study, 0.1 mL of C12-18AS Na (CAS 68955-19-1, analytical purity 6%) was instilled into the eye of 6 New Zealand white rabbits similar to OECD Guideline 405 (Connor, 1979). Eye reactions were scored 24, 48 and 72 h after treatment. The mean (24, 48 and 72 h reading) cornea, iris, conjunctivae and chemosis scores were 0, 0, 0.9 and 0.1. The conjunctival effects reversed within 72 h and chemosis within 48 h. Thus the substance was not irritating to eyes at a concentration of 6%.

There is one relevant study for C12-16AS Na (CAS 73296-89-6) available addressing eye irritation.

An OECD guideline 405 study was performed with 0.1 mL pure C12-16 AS Na (CAS 73296-89-6, analytical purity 30%) on three New Zealand White rabbits (Tortajada, 1997). The observation period was 21 days. Eye reactions were scored 1, 24, 48 and 72 h after treatment. Further observations were performed on days 7, 14, and 21 after application. The mean (24, 48 and 72 h reading) cornea, iris, conjunctivae and chemosis scores were 1, 0.2, 2.8 and 3.6. The iritic effects reversed within 72 h and chemosis within the 21 day observation period. The effects observed on cornea and the redness of the conjunctiva was not fully reversible within 21 days. Thus the substance produced irreversible effects on the eye at a concentration of 30% within this study.

Setting of SCLs for eye irritation

As corrosion and irritation depends on the concentration of the substance in a solvent, further studies with lower concentrations of the test substance were also considered to assess whether specific concentration limits can be set. For this purpose, one study with C12-13AS K (CAS 91783-22-1) and two studies with C10-16AS Na (CAS 68585-47-7) with a concentration range of 10 to 22% were evaluated.

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 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, 1980a) 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 (score 1) and conjunctival redness was still present in 2/3 animals (both score 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, 1980b). 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 of 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%.

Further available data

Next to the above mentioned studies further studies with C12-18AS Na (CAS 68955-19-1), performed with lower concentrations of the test item are available. These study reports however provide only limited data on the method and/or the individual scores and are therefore not suited for classification purposes. Therefore only a short summary of those studies is reported in the following text.

The study conducted with C12-18AS Na (CAS 68955-19-1, analytical purity 35%) was performed at final concentrations of 5% with 5 rabbits (Henkel, 1981). The test substance was applied once as drop. Eye reactions were observed which were reversible within 48 h.

Another study with C12-18AS Na (CAS 68955-19-1, analytical purity 35%) was performed as Draize test at a final concentration of 5%. 0.1 mL was applied to the eyes of 4 rabbits (Henkel, 1985). No corneal reactions were observed. Conjunctival effects were observed from 1 to 72 h after application and reversed within 144 h. Iritic effects were observed at the 24 h reading time point only. No individual scores were reported. Another Draize test with C12-18AS Na (CAS 68955-19-1) was performed with 0.1mL of the test substance at concentrations ranging from 0.5 to 20% without rinsing and with concentrations of 10 and 20% with rinsing of the eye (Henkel, 1977). No eye reactions were observed at and below 1%. At and above 5 % the test substance was judged to be moderately irritating. At and above concentrations of 10% the effects did not reverse completely within 21 days.

 

[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:
A reliable OECD guideline study was chosen.

Justification for selection of eye irritation endpoint:
Reliable OECD guideline study

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 Irritation Category 2, H315 and Eye Dam.1, H318, respectively. 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.

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).