Sulfuric acid, mono-C16-18-alkyl esters, sodium salts

Endpoint summary

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 different studies regarding skin and eye irritation/corrosion with C16-18AS Na (CAS 68955-20-4) available. Supportive a read-across from structurally related AS, i.e. C12-18AS Na (CAS 68955-19-1) for skin irritation and C12-16AS Na (CAS 73296-89-6) 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 physico-chemical, 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 property 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, ecotoxicological 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 program carrying out Human and Environmental Risk Assessments (HERA [2]), further supporting the read across approach between structurally related AS.

 

Skin irritation

There are three relevant studies with C16-18AS Na (CAS 68955-20-4) and one relevant study for the read-across substance C12-18AS Na (CAS 68955-19-1) available addressing skin irritation.

In-vivo skin irritation of C16-18AS Na

A study with C16-18AS Na (CAS 68955-20-4, analytical purity 55%) was performed according to OECD guideline 404 on 5 rabbits (strain: Kleinrusse Chbb:HM) (Kästner, 1986). 0.5 g of the unchanged test item was applied for 4 h under occlusive conditions and skin reactions were scored immediately, 24, 48 and 72 h after removal of the patch and on day 7. The mean erythema score (24, 48 and 72 h reading) and the mean edema score were 1.3 and 0.6, respectively. Both effects were fully reversed within the 7 days observation period. Based on the result of this study the test substance is not irritating at a concentration of 55% a.i.

Another study with C16-18AS Na (CAS 68955-20-4, analytical purity 94.3%) was performed according to OECD guideline 404 on 5 rabbits (strain: Kleinrusse Chbb:HM)( Kästner, 1987) 0.5 mL of the diluted test item (25%) was applied for 4 h under occlusive conditions to the rabbit skin and skin reactions were scored immediately after removal of the patch, after 24, 48 and 72 h and on day 7, 10, 14, 17 and 21. The mean erythema score (24, 48 and 72 h reading) and the mean edema score were 1.6 and 0.7, respectively. Both effects were fully reversible during the observation period. Based on the result of this study the test substance is not irritating at a concentration of 25% a.i. In-vitro skin irritation of C16-18AS Na

A combined OECD guideline 431 and OECD guideline 439 in vitro study with reconstructed human epidermis (RHE) was performed with 25% C16-18AS Na (CAS 68955-20-4) (Remmele, 2012a). When cells were exposed for 3 and 60 minutes without a post exposure period (corrosion test) the cell viabilities were 103% and 107%, respectively. The cell viability after a 60 min exposure and 42 h post exposure period (irritation test) was 117%. Thus, 25% C16-18AS Na was neither corrosive nor irritating in this in vitro study.

In conclusion, even when exposed under occlusive conditions C16-18AS Na (CAS 68955-20-4) does not need to be classified as skin irritant up to 55%. However, no studies are available with C16-18AS Na (CAS 68955-20-4) at higher concentrations. Therefore a read-across from C12-18AS Na (CAS 68955-19-1, analytical purity 89%) was performed.

In-vivo skin irritation of C12-18AS Na

The study conducted with C12-18AS Na (CAS 68955-19-1) 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 observed for a period of 14 days for erythema and edema. The mean erythema score and the mean edema score (24, 48 and 72 h reading) were 3 and 2.3, respectively. Both effects were fully reversed within the 14 days observation period. 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.

 

Conclusion on the skin irritating properties of C16-18AS Na (CAS 68955-20-4)

C12-18AS Na contains up to 65 % C12AS which represents the carbon chain length with the highest irritation potential of the members of the AS Category. Thus, this read-across is conservative and the hazard of the target substance might be overestimated. Nevertheless in absence of data C16-18AS Na (CAS 68955-20-4) will be classified as R38 and H315, respectively at concentrations greater 55%. Concentrations greater 55% will also be classified as “may cause respiratory irritation” (STOT SE3, H335 and R37, respectively) in case the substance is available as neat powder. No classification is required at or below 55% C16-18AS Na (CAS 68955-20-4).

 

Eye irritation

There are seven relevant studies with C16-18AS Na (CAS 68955-20-4) available addressing eye irritation. Moreover, a supportive read-across from structurally related AS, i.e. C12-16AS Na (CAS 73296-89-6) was performed.

In-vivo eye irritation of C12 -16AS Na and C16-18AS Na

There is one relevant study for the read-across substance C12-16AS Na (CAS 73296-89-6) available and two relevant in-vivo studies with C16-18AS Na (CAS 68955-20-4) itself addressing eye irritation.

An OECD guideline 405 study was performed with 0.1 mL pure Na C12-16 ASO4 (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.

In an OECD guideline 405 study 0.1 mL of a 25% aqueous solution of C16-18AS Na (CAS 68955-20-4) was applied to one eye of each of four rabbits (Kästner, 1987b). Eye reactions were scored 1, 6, 24, 48 and 72 h and 1, 10, 14, 17 and 21 days after application. The mean (24, 48 and 72 h reading) cornea, iris, conjunctivae and chemosis scores were 0.8, 0, 2.3 and 0.4. All effects were fully reversible. The test substance does not meet the classification criteria of Directive 67/548/EEC but the classification criteria of Regulation (EC) No 1272/2008 (Eye Irritating Cat2). Thus, the results of this study indicate the concentration of 25% used within this study to be the borderline for classification purposes under CLP.

A second study performed similar to OECD guideline 405 was performed on two animals only (Kästner, 1986b). Therefore data of this study can only be interpreted with caution and are used in a weight of evidence approach. 0.1 g of C16-18AS Na (CAS 68955-20-4, analytical purity 55%) was applied to one eye of each rabbit. Eye reactions were scored 1, 6, 24, 48, 72 and 144 h after application. The mean (24, 48 and 72 h reading) cornea, iris, conjunctivae and chemosis scores were 0.7, 0, 1.8 and 0.2. All effects were fully reversible. The results of this study indicate the concentration of 55% to be not irritating to the eyes according to the classification criteria of Directive 67/548/EEC and Regulation (EC) No 1272/2008.

Based on these in-vivo studies C16-18AS Na (CAS 68955-20-4) does not produce severe damage to the eye at concentrations below or equal 55%. According to Directive 67/548/EEC no classification at all is required below or equal 55%. However, the substance might be classified for eye irritation according to Regulation (EC) No 1272/2008 based on the study results of Kästner (1987b). To further explore the eye irritating properties of C16-18AS Na (CAS 68955-20-4) several in-vitro studies were performed.

In-vitro eye irritation of C16-18AS Na

There are three bovine corneal opacity permeability studies with C16-18AS Na (CAS 68955-20-4) available. In the first study 3 isolated corneas were incubated for 4 h with 20% aqueous solutions of C16-18AS Na in two independent experiments (Remmele, 2012b). The corneal opacity and the permeability of the cornea were determined subsequently and the IVIS score was calculated to quantify eye irritation. The IVIS scores were 69 and 88. Thus both values exceeded the IVIS cut-off value of 55 and 20% aqueous solutions of C16-18AS Na and were able to induce serious eye damage under the conditions of the study. However, it should be noted that the exposure duration of this study was 4 h as recommended in OECD Guideline 437 for solids. The recommended exposure duration for liquids is 10 min. Thus this study is not suited for classification purposes as the exposure duration was far too long.

When tested according to the standard protocol of OECD Guideline 437, i.e. incubation of cornea for 10 min with 120 min post exposure period, the IVIS score calculated as indicator of eye damage was 6 and 3.3 at 10 and 20% aqueous solution (Remmele, 2012c). When extending the exposure period to 60 min and decreasing the post exposure time to 60 min the calculated IVIS scores were 38 and 20.1 (Remmele, 2012c).

The third BCOP study according to the standard protocol for liquid surfactants of OECD Guideline 437, i.e. incubation of cornea for 10 min with 120 min post exposure period , the IVIS score calculated was 0 at 2% aqueous solution (Remmele, 2015). The negative and positive control proved the validity of the study.

In conclusion, the BCOP studies according the standard protocol of OECD Guideline 437 for liquids showed that application of 2, 10 and 20% aqueous solution of C16-18AS Na (CAS 68955-20-4) does not result in severe eye damage. Considering the decision criteria laid down in the OECD Guideline 437 an eye irritating potential cannot be excluded. The eye irritating potential of aqueous solutions of C16-18AS Na (CAS 68955-20-4) was therefore further assessed in two studies performed similar and according to OECD 492.

A scientific reliable study, performed similar to the OECD draft proposal for reconstructed human cornea-like epithelium (RhCE) test method, was conducted with neat C16-18AS Na (CAS 68955-20-4) and with a 25% aqueous solution of C16-18AS Na (Remmele, 2012d). Only a summary report is available where details on the test system and the method were not provided. Therefore data of this study are used in a weight of evidence approach. The tissue samples were incubated either for 90 min with the undiluted, solid test material or for 30 min with the aqueous solution. The cell viability was 5% of the negative control when incubated with the neat/solid test material and 63% when incubated with the aqueous solution. In conclusion the neat substance showed an eye irritation potential in the EpiOcular eye irritation test while 25% aqueous solutions did not fulfill the criteria for eye irritation.

A second study according to OECD Guideline 492 was conducted with 20% aqueous solution of C16-18AS Na (Remmele, 2015). After assuring that the test substance was not able to reduce MTT directly reconstructed human cornea-like epithelium samples were incubated for 30 min with the test material. After a post-exposure of 120 minutes the cell viability was 87.6% of the negative control. The positive control methyl acetate resulted in a remaining cell viability of 31.7% thereby showing the acceptance criteria for a positive control of below 60%. In conclusion, in the in the EpiOcular test 20% aqueous solutionn did not fulfil the criteria for eye irritation.

 

 

Conclusion on the eye irritating properties of C16-18AS Na (CAS 68955-20-4)

Based on the read-across a worst case classification of C16-18AS Na with R41/H318 according to DSD/CLP does apply. 55% C16-18AS Na produced slight eye irritation in-vivo not leading to a classification for eye irritation according to DSD and CLP. However, due to the study results of Kästner 1987b a classification for eye irritation Cat 2, H319 is required at 25% C16-18AS Na. In the relevant EpiOcular tests (Remmele, 2012d and 2015) 20 and 25% aqueous solutions of C16-18AS Na need not to be classified for eye irritation. Since the data for 20% clearly show that no eye irritation potential has to be expected, a cut off value for eye irritation was established at greater than 20%.

According to DSD > 55% C16-18AS Na (CAS 68955-20-4) needs to be classified as Xi, R41 while ≤55% C16-18AS Na (CAS 68955-20-4) needs no classification at all.

According to CLP > 55% C16-18AS Na (CAS 68955-20-4) needs to be classified as H318, Eye Dam. 1. Based on a weight of evidence approach >20% - ≤55% C16-18AS Na (CAS 68955-20-4) needs to be classified as H319, Eye Irrit. 2 according to CLP. At or below 20% no classification at all is required.

No data on respiratory irritation are available. AS is mainly used in liquid media and due to its very low vapour pressure [2] inhalation is not viewed as a significant route of exposure. Inhalation of AS may occur by inhalation of aerosols generated by spray cleaners or by inhalation of detergent dusts (e.g. washing powder). In both cases the substance will be used in low concentrations. However in case the substance is available as neat powder the substance will also be classified as STOT Single exp. Cat 3 according to CLP and according to DSD as Xi, R37 irritating to the respiratory system at concentrations exceeding 55%.

[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:
Reliable OECD guideline study.

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 the neat test substance needs to be classified with Xi, R38/R41 while no classification is required at or below 55% C16-18AS Na (CAS 68955-20-4).

According to the classification criteria of Regulation (EC) No 1272/2008 the neat test substance needs to be classified with Skin Irritation Category 2, H315 and Eye Dam.1, H318, respectively. At or below 55% C16-18AS Na (CAS 68955-20-4) no classification for skin irritation remains.It could be further shown with experimental data on eye irritation that according to CLP >20 % - ≤55% C16-18AS Na (CAS 68955-20-4) needs to be classified as H319, Eye Irrit.2. At or below 20% no classification at all is required according to CLP. Hence, the Generic Concentration Limits (GCLs) can be substituted by the mentioned specific ones (SCLs).

 

Concentrations greater 55% will also be classified as “may cause respiratory irritation” (STOT SE3, H335 and R37, respectively) in case the substance is available as neat powder.