Sulfuric acid, mono-C12-14 (even numbered)-alkyl esters, compds. with ethanolamine

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

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study with acceptable restrictions.

Qualifier:

equivalent or similar to guideline

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 or test system 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:

other: mean on 6 animals

Time point:

other: 24 + 72 h

Score:

2.2

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: no single values are available

Irritation parameter:

edema score

Basis:

other: mean on 6 animals

Time point:

other: 24 + 72 h

Score:

1.7

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: not singles results are available

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 vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study with acceptable restrictions.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

no

Species:

rabbit

Strain:

other: Kleinrusse

Details on test animals or tissues and environmental conditions:

According to Guideline.

Vehicle:

not specified

Controls:

not required

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

n.a.

Observation period (in vivo):

21 days

Number of animals or in vitro replicates:

4

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24+48+72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24+48+72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24+48+72 h

Score:

2.6

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24+48+72 h

Score:

1.1

Max. score:

4

Reversibility:

fully reversible within: 14 days

Cornea

           time (hrs)                           time (days)
           1      6       24      48     72     7     10     14     17      21
mean A     0.75   0.75    1       1      1      1     0.75   0.75   0.75    0.75
mean B     1.5    1.25    4       3.25   3.25   2.75  2.25   2.25   2.25    1.75

A = cloudiness grade
B = cloudiness surface


Cornea (0.5 % aqueous fluorescein): mean 100 or 40 after 24 hrs or 21  days p.a.


Conjunctivae

           time (hrs)                           time (days)
           1      6       24      48     72     7     10     14     17      21
mean A     1      2       2.25    2.75   2.75   2.25  1.5    1.25   1.25    1.25
mean B     1.25   1       1.25    1      1      0.5   0.25   0      0       0
mean C     3      3       3       3      3      1     2.25   1.75   1.75    0.75

A = erythema
B = chemosis
C = exsudation

Reversibility: no

Interpretation of results:

irritating

Remarks:

Migrated information R41 Criteria used for interpretation of results: EU

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

There is one relevant skin irritation study with C12-14AS MEA (CAS 90583-16-7) available. Additionally, a read across from the structurally related AS, i.e. C12AS Na (CAS 151-21-3) for skin irritation and C12AS Na (CAS 151-21-3), C12-16AS NH4 (CAS 90583-12-3), 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 counterion. 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 programme carrying out Human and Environmental Risk Assessments (HERA [2]), further supporting the read across approach between structurally related AS.

For a discussion on the impact of the MEA content on the skin and eye irritating properties please refer to the respective sub sections below.

Skin irritation

The key study was conducted with C12AS Na (CAS 151-21-3, analytical purity 100%) similar to OECD Guideline 404 under occlusive conditions (Esposito, 1976). Each of 6 New Zealand White rabbits was exposed for 24 h to 0.5 mL of the unchanged test item and 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, respectively. Both were not reversible within 72 h. When using the higher value of the 24 and 72 h time points as the 48 h value (per animal) the mean erythema and edema score of all animals were 2.4 and 2.2, respectively. Thus, the key study indicated that alkyl sulfates are irritating to skin.

This is supported by available data of C12-14AS MEA (CAS 90583-16-7) demonstrating that concentrations up to 40% do not result in irreversible damage to the skin. The study conducted with C12-14AS MEA (CAS 90583-16-7, analytical purity 40%) was performed according to OECD Guideline 404 under semi-occlusive conditions (Clouzeau, 1990). Each of three New Zealand White rabbits was exposed for 4 h to 0.5 mL of the unchanged test item and skin reactions were scored until total recovery on day 11. Skin reactions were scored 24, 48 and 72 h after termination of treatment and daily thereafter. The mean erythema and edema score after 24, 48 and 72 h were 3.0 and 0.67. The skin reactions were fully reversible within 10 days.

 

MEA (non-ionic) is classified inter alia as skin corr. 1B; H314 according to Regulation EC 1272/2008. According to the guidance on the application of the CLP criteria (Section 3.2.3.3), a mixture shall be classified as Skin Corr. 1B, H314, if the sum of all ingredients of a mixture classified as Skin Corr. 1B, H314 is ≥ 5% and as Skin Irrit.2, H315 if the sum of all ingredients of a mixture classified as Skin Corr. 1B, H314 is ≥ 1% but < 5%.

 

The concentration of freely available MEA in C12-14AS MEA (CAS 90583-16-7) is below 1%. Thus, unbound MEA will not contribute to skin irritation/damage.

 

Additionally, a survey on the classification of different MEA salts (MEA-HCl, MEA-lauryl sulfate, MEA-cocoate, MEA-laureth sulfate and MEA-Undecylenate) on ECHAs website was performed. The result is summarized in the table below and showed that MEA salts are not corrosive to skin but are able to induce skin irritation. 

 

Name	Abbreviation	CAS Number	Major C&L*
2-hydroxyethylammonium chloride	MEA-HCl	2002-24-6	Skin Irrit. 2 Eye Irrit. 2 STOT SE 3
Fatty acids, coco, compds. with ethanolamine	MEA -Cocoate	66071-80-5	Skin Irrit. 2 Eye Irrit. 2
undec-10-enoic acid, compound with 2-aminoethanol (1:1)	MEA-Undecylenate	56532-40-2	Not Classified
(2-hydroxyethyl)ammonium dodecylsulfate	MEA-Lauryl Sulfate	4722-98-9	Skin Irrit. 2 Eye Irrit. 2 And Skin Irrit. 2 Eye Dam. 1
MEA Laureth Sulphate	MEA-Laureth Sulfate	68184-04-3	Skin Irrit. 2 Eye Irrit. 2 And Skin Irrit. 2 Eye Dam. 1

* classification and labelling on ECHAs C&L inventory notified by the most notifiers

 

Thus, C12-14AS MEA (CAS 90583-16-7) is classified as skin irritating Category 2, H315 according to Regulation 1272/2008/EC and R38 according to Directive 67/548/EEC.

 

Eye irritation

In an OECD Guideline 405 study (Kästner, 1987) 0.1 mL of C12AS Na (CAS 151-21-3, analytical purity 25%) 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 (Kästner, 1988) 0.1 g of with C12-16AS NH4 (CAS 90583-12-3, analytical purity 30%) was applied to the eye of one rabbit (strain: Kleinrusse).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 %.

Establishment of SCLs

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, 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 without rinsing (Braun, 1978).

In a second experiment with an 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 indicated signs of irritation after 21 days. However, irritation showed a clear tendency to decrease with time. No reading on day 28 was possible due to death of the rabbit. 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, 1980a) on 3 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, 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%.

Due to the MEA content in C12-14AS MEA (CAS 90583-16-7) the relevance of these specific concentration limits was assessed. In a study performed similar to OECD Guideline 405 0.1 mL of C12-14AS MEA (CAS 90583-16-7, analytical purity 33%) was applied to one eye of each of four rabbits at a concentration of 0.5, 1, 5, 10 and 20% based on active ingredient (Kästner, 1977). Another four rabbits were treated with 10 and 20% based on active ingredient, respectively. Eyes of these additional treatment groups were rinsed with 60 mL tap water 10 seconds after instillation. Eye reactions were scored 2, 6, 24, 48 and 72 h as well as 4, 7, 10, 12, 18 and 21 days after application according to Draize. The results were reported as relative mean values (%) of the maximum possible reaction (100%). No corneal opacity, iris effects or chemosis was observed at any tested concentration and time point. The only finding was conjunctival redness at 10 and 20%. This finding was reversible within 48 and 72 h, respectively. Conjunctival reactions were lower when eyes were rinsed. Although no individual scorings are provided data show that concentrations of 20% C12-14AS MEA (CAS 90583-16-7) does not trigger severe eye damage or irritating effects leading to a classification. Thus, the established SCLs of the alkyl sulfate category are valid for C12-14AS MEA (CAS 90583-16-7) as well. To further support this assumption a BCOP and an epioccular study are currently ongoing.

Respiratory inhalation

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, 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.

 

[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] SIDS initial assessment report, (2013);

http://webnet.oecd.org/HPV/UI/SIDS_Details.aspx?key=8aefe41b-8499-4052-943f-f6dd6f8c5997&idx=0

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 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.

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).