Registration Dossier

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
<10% No Classification

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

There is no study regarding skin and eye irritation/corrosion available for C12-14 AS MIPA (CAS 85681-66-9). Therefore this endpoint is covered by read across to structurally related alkyl sulfates (AS), i.e. C12-16 AS NH4 (CAS 90583-12-3) and C12 AS Na (CAS 151-21-3) for skin irritation and C12 AS Na (CAS 151-21-3), C12-16 AS NH4 (CAS 90583-12-3), C10-16 AS Na (CAS 68585-47-7) and C12-13 AS K (CAS 91783-22-1) for eye irritation. 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 physicochemical, 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 program carrying out Human and Environmental Risk Assessments (HERA [2]), further supporting the read across approach between structurally related AS.

 

Skin irritation

Regarding skin irritation one relevant study is available for the read-across substance C12-16 AS NH4 (CAS 90583-12-3) and for C12 AS Na (CAS 151-21-3).

The key study conducted with C12 AS Na (CAS 151-21-3, analytical purity 100%) was performed similar to OECD Guideline 404 under occlusive conditions (BASF, 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. No scoring was done 48 h after application. 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.

The study conducted with C12-16 AS NH4 (CAS 90583-12-3, analytical purity 30%) was performed according to OECD Guideline 404 under semi-occlusive conditions (BASF, 1987a). Each of five Kleinrusse white rabbits was exposed for 4 h to 0.5 mL of the unchanged test item and was observed for a period of 21 d for erythema and edema. Skin reactions were scored 24, 48 and 72 h after termination of treatment. The mean erythema and edema score after 24, 48 and 72 h were 3.9 and 3.5. The skin reactions were fully reversible within the 21 day observation period.

 

Conclusion on the skin irritating properties of C12-14 AS MIPA (CAS 85681-66-9)

Based on the results mentioned above the data on the read across substances justify a classification of C12-14 AS MIPA (CAS 85681-66-9) for skin irritation. According to CLP ≥ 10%C12-14 AS MIPA (CAS 85681-66-9) needs to be classified as H315, Skin Irrit. 2. No classification is required below 20% and 10% C12-14 AS MIPA (CAS 85681-66-9), respectively.

 

Eye irritation

No data are available for the neat substance allowing a definitive classification of C12-14 AS MIPA (CAS 85681-66-9). Therefore a read-across from C12 AS Na (CAS 151-21-3), C12-16 AS NH4 (CAS 90583-12-3), C12-13 AS K (CAS 91783-22-1) and C10-16 AS Na (CAS 68585-47-7) was performed.

The key study was performed according to OECD guideline 405 with 0.1 mL of C12 AS Na (CAS 151-21-3, analytical purity 25%) (BASF, 1987b). The test substance was applied to one eye of each of four rabbits (strain: Kleinrusse Chbb:HM). Eye reactions were scored 1, 6, 24, 48 and 72 h and 7, 10, 14, 17 and 21 days after application. The mean (24, 48 and 72 h reading) cornea, iris, conjunctivae and chemosis scores were 1, 0, 2.6 and 1.1. The corneal and the conjunctival findings did not revers fully until days 21. Thus the test item produced irreversible effects on the eye at a concentration of 25%.

In an OECD guideline 405 study 0.1 g of with C12-16 AS NH4 (CAS 90583-12-3, analytical purity 30%) was applied to the eye of one rabbit (strain: Kleinrusse) (BASF, 1988). The observation period was 21 days. Eye reactions were scored 24, 48 and 72 h after application. The mean (24, 48 and 72 h reading) cornea, iris, conjunctivae and chemosis scores were 1, 0, 2 and 1. The corneal and the conjunctival findings as well the chemosis did not revers fully until days 21. Thus the test item produced irreversible effects on the eye at a concentration of 30%.

In a further OECD guideline 405 study 0.1 mL of C10-16 AS Na (CAS 68585-47-7, analytical purity 30%) was applied to one eye of each of three rabbits (Hansa, 1984). Eye reactions were scored 24, 48 and 72 h and 7 days after application. The mean (24, 48 and 72 h reading) cornea, iris, conjunctivae and chemosis scores were 2.3, 1, 2.3 and 2.9. The findings did not fully revers within 7 days. Thus the test item produced irreversible effects on the eye at a concentration of 30%.

 

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 read across substances were also considered to assess whether specific concentration limits can be set.

For this purpose, two studies with C10-16 AS Na (CAS 68585-47-7) and one study with C12-13 AS K (CAS 91783-22-1) with a concentration range of 10 to 22% were evaluated.

In the study with C12-13 AS 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 (P&G, 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 sec 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 C10-16 AS Na (CAS 68585-47-7, analytical purity 10%) was performed similar to OECD guideline 405 (Stepan, 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 (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 C10-16 AS Na (CAS 68585-47-7, analytical purity 10%) was performed similar to OECD guideline 405 (Stepan, 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%.

 

Conclusion on the eye irritating properties of C12-14 AS MIPA (CAS 85681-66-9)

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%. Since the available data of the read-across substance C10-16 AS Na (CAS 68585-47-7) indicates no eye irritation potential at a concentration of 10%, no classification is required below 10% C12-14 AS MIPA (CAS 85681-66-9).

According to CLP ≥ 20% C12-14 AS MIPA (CAS 85681-66-9) needs to be classified as H318, Eye Dam. 1. Based on a weight of evidence approach ≥ 10 % - < 20% C12-14 AS MIPA (CAS 85681-66-9) needs to be classified as H319, Eye Irrit. 2 according to CLP. Below 10% 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 at concentrations exceeding 20%.

Influence of counter-ions on irritating potential

The effects on health of isopropanolamine (MIPA) are dominated by its corrosive properties. MIPA is listed in Annex VI of EG 1272/2008 as Skin Corrosive Category 1B, H314. Further information indicates MIPA to be moderately toxic after dermal application. During the registration process for 2010 MIPA was also classified as harmful in contact with skin (Acute Toxicity Cat 4, H312 according to Regulation 1272/2008/EC). The leading effects of the alkyl ether sulfates are skin irritating and eye corrosive properties leading to a self-classification according to Regulation 1272/2008/EC for pure alkyl ether sulfates as Skin Irritating, Cat 2, H315 (causes skin irritation) and Eye Damaging Cat 1, H318 (causes serious eye damage). As both, MIPA and AS (C12-14) MIPA are classified as being corrosive to the eyes; the contribution of MIPA to the endpoint of eye corrosion/irritation is negligible. However, MIPA may contribute to the AS (C12-14) MIPA toxicity regarding the endpoint skin corrosion.

With regard to the skin corrosive potential a skin corrosion study with MIPA was available. Rabbits were treated with the pure substance for 1, 5 and 15 min as well as 20 h under occlusive conditions. After the application time of 1, 5 and 15 min the skin was washed once with Lutrol and once with diluted Lutrol (50%). The animals were observed for 8 days and skin changes were recorded daily. The report describes findings after 24 h and at the end of the observation period (8 days). For a final evaluation, the findings after 48 h and 72 h from the raw data were additionally taken into account. The test substance caused bleeding after application for 5 (3/6 animals) and 15 min (4/6 animals). At the end of the observation period of 8 days scale and crust formation was noted. One animal of the 15 min application group showed anemic necrosis. The 20 h application led to severe edema and erythema and caused grey-blackish, re-locatable necrosis beyond the application area. This leads to a self-classification of MIPA for Skin Corrosion Cat 1B, H314.

The findings observed during the skin corrosion study with MIPA are most likely attributable to its high basicity of MIPA (pH-value of approx. 11 to 12). As the pH-value of C12-14 AS MIPA is moderate, the skin corrosive properties of C12-14 AS MIPA will not be triggered by the basicity of MIPA but by the AS moiety. Therefore the classification as Skin Irritating, Cat 2, H315 is justified for the AS category member C12-14 AS MIPA.

 

[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

[3] Reference available at:

http://webnet.oecd.org/HPV/UI/SIDS_Details.aspx?Key=2c80d506-86bf-4719-be9b-d922022506ec&idx=0

Justification for classification or non-classification

According to the classification criteria of Regulation (EC) No 1272/2008 the test substance needs to be classified with 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) 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 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).