Alcohols, C9-11, branched and linear, ethoxylated, sulfates, sodium salts

Endpoint summary

Description of key information

Skin irritation / corrosion (in vivo, similar OECD 404): irritating

Conclusion based on data with alcohols, C9-11, branched and linear, ethoxylated, sulfates, sodium salts (CAS No. 160901-28-0, EC No. 500-465-4) and considering all available data on skin irritation / corrosion in the Alkyl Ether Sulfate (AES) category in a Weight-of-Evidence approach.

 

Eye irritation: serious eye damage

Read-across based on grouping of substances (category approach) considering all available data on eye irritation in the AES category in a Weight-of-Evidence approach.

Specific Concentration Limits (SCL):

5% - <10% Eye Irrit. 2, H319

< 5% No Classification

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

Occlusive dressing; 24 h exposure; 48 h scoring is missing. Only 72 h observation time.

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

According to Guideline.

Type of coverage:

occlusive

Preparation of test site:

other: shaved and abraded

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:

animal #1

Time point:

24 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: Only intact skin values were used for calculation; only 72 h observation time

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: Only intact skin values were used for calculation; only 72 h observation time

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: Only intact skin values were used for calculation; only 72 h observation time

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: Only intact skin values were used for calculation; only 72 h observation time

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: Only intact skin values were used for calculation; only 72 h observation time

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: Only intact skin values were used for calculation; only 72 h observation time

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: Only intact skin values were used for calculation; only 72 h observation time

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: Only intact skin values were used for calculation; only 72 h observation time

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: Only intact skin values were used for calculation; only 72 h observation time

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: Only intact skin values were used for calculation; only 72 h observation time

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: Only intact skin values were used for calculation; only 72 h observation time

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: Only intact skin values were used for calculation; only 72 h observation time

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: Only intact skin values were used for calculation; only 72 h observation time

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #6

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: Only intact skin values were used for calculation; only 72 h observation time

Irritation parameter:

edema score

Basis:

animal #1

Time point:

72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: Only intact skin values were used for calculation; only 72 h observation time

Irritation parameter:

edema score

Basis:

animal #2

Time point:

72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: Only intact skin values were used for calculation; only 72 h observation time

Irritation parameter:

edema score

Basis:

animal #3

Time point:

72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: Only intact skin values were used for calculation; only 72 h observation time

Irritation parameter:

edema score

Basis:

animal #4

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #6

Time point:

72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: Only intact skin values were used for calculation; only 72 h observation time

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

1.6

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: Only intact skin values were used for calculation; 48 h scoring is extrapolated.

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

1.1

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: Only intact skin values were used for calculation; 48 h scoring is extrapolated.

Interpretation of results:

other: Skin irrit. 2, H315. Classification according to Regulation (EC) No. 1272/2008 (CLP/EU GHS), applying a precautionary approach.

Conclusions:

In the present in vivo skin irritation study in the rabbit, the test substance induced erythema and oedema in the 6 test animals. The scores were low, but the effects were not reversible within the 72 h observation period. Applying a precautionary principle, it is concluded that the test substance is irritating to the skin.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

weight of evidence

Justification for type of information:

Please refer to the category justification provided in the category object.

Irritation parameter:

erythema score

Time point:

24/48/72 h

Remarks on result:

other: Irritating based on all available skin irritation data in the Alkyl Ether Sulfates (AES) category.

Irritation parameter:

edema score

Time point:

24/48/72 h

Remarks on result:

other: Irritating based on all available skin irritation data in the Alkyl Ether Sulfates (AES) category.

For a detailed assessment of the skin irritation / corrosion potential of the Alkyl Ether Sulfates (AES) category, please refer to the category justification attached to the category object.

Interpretation of results:

other: Skin irrit. 2, H315. Classification according to Regulation (EC) No. 1272/2008 (CLP/EU GHS).

Conclusions:

Applying read-across based on grouping of substances (category approach), an irritating potential is predicted for the target substance.

Executive summary:

The available data on skin irritation / corrosion in the Alkyl Ether Sulfates (AES) category indicate a skin irritation potential for the target substance. As explained in the category justification, the differences in molecular structure and composition between the target substance and the members of the AES category are unlikely to lead to differences in the skin irritation / corrosion potential.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Justification for type of information:

Please refer to the category justification provided in the category object.

Irritation parameter:

cornea opacity score

Time point:

24/48/72 h

Remarks on result:

other: Serious eye damage based on all available eye irritation data in the Alkyl Ether Sulfates (AES) category.

Irritation parameter:

iris score

Time point:

24/48/72 h

Remarks on result:

other: Serious eye damage based on all available eye irritation data in the Alkyl Ether Sulfates (AES) category.

Irritation parameter:

conjunctivae score

Time point:

24/48/72 h

Remarks on result:

other: Serious eye damage based on all available eye irritation data in the Alkyl Ether Sulfates (AES) category.

Irritation parameter:

chemosis score

Time point:

24/48/72 h

Remarks on result:

other: Serious eye damage based on all available eye irritation data in the Alkyl Ether Sulfates (AES) category.

For a detailed assessment of the eye irritation potential of the Alkyl Ether Sulfates (AES) category, please refer to the category justification attached to the category object.

Interpretation of results:

other: Eye damage 1, H318. Classification according to Regulation (EC) No. 1272/2008 (CLP/EU GHS).

Conclusions:

Applying read-across based on grouping of substances (category approach), a potential to induce serious eye damage is predicted for the target substance.

Executive summary:

The available data on eye irritation in the Alkyl Ether Sulfates (AES) category indicate a potential to induce serious eye damage for the target substance. As explained in the category justification, the differences in molecular structure and composition between the target substance and the members of the AES category are unlikely to lead to differences in the eye irritation potential.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation / corrosion

Data on skin irritation / corrosion are available for alcohols, C9-11, branched and linear, ethoxylated, sulfates, sodium salts (CAS No. 160901-28-0, EC No. 500-465-4) as well as several member substances of the Alkyl Ether Sulfates (AES) category.

 

Study with alcohols, C9-11, branched and linear, ethoxylated, sulfates, sodium salts (CAS No. 160901-28-0, EC No. 500-465-4)

The skin irritation potential of alcohols, C9-11, branched and linear, ethoxylated, sulfates, sodium salts (CAS No. 160901-28-0, EC No. 500-465-4) was investigated in a study similar to OECD guideline 404 (Huntsman, 1977b). The study was performed with an occlusive dressing and a total observation period of only 72 h. Additional deviations from the current OECD guideline 404 include a 24 h exposure period and a lack of scoring at the 48-h reading time point. 0.5 mL of the unchanged test substance (concentration of alcohols, C9-11, branched and linear, ethoxylated, sulfates, sodium salts (CAS No. 160901-28-0, EC No. 500-465-4) in the test material: 30%) was applied to the shaved and abraded skin of six New Zealand White rabbits for 24 h under occlusive conditions. No further details regarding the study design are available. The test substance induced erythema and oedema in the six animals. The scores were low, but the effects were not reversible within the 72-h observation period. In a worst-case assessment, the test substance was concluded to be irritating to the skin. Due to the methodological deficiencies, the study cannot be used to address skin irritation / corrosion as stand-alone information and the assessment of the endpoint is also based on available data obtained with other AES category member substances.

 

Studies in the AES category

Additional studies on skin irritation / corrosion are available for the following AES substances:

 

Table 1: Database on skin irritation / corrosion in the Alkyl Ether Sulfates (AES) category

CAS / EC Nos.	Substance	Study or Report No.	Study protocol (adopted in)	Concentration in test material [%]	Hazard conclusion
‘Linear’ subgroup
1471312-55-6 / 939-523-2	Alcohols, C8-10, ethoxylated, sulfates, sodium salts	121484	OECD 439	100	Irritating or corrosive
		122043	OECD 431 (EpiDerm)	100	Not corrosive
68585-34-2 / 500-223-8	Alcohols C10-16, ethoxylated (1-2,5 EO) sulphated, sodium salts	000504/1	Similar OECD 404	68	Irritating
		82-003E	Similar OECD 404	25	Irritating
		82-003B	Similar OECD 404	25 - 30	Irritating
		A/S/12431	Similar OECD 404	70	Irritating
		18957	OECD 404	58.5	Irritating
		4299	Similar OECD 404	10	Not irritating
		4306	Similar OECD 404	1	Not irritating
68891-38-3 / 500-234-8	Alcohols, C12-14, ethoxylated, sulfates, sodium salts	R9400637	OECD 404	70	Irritating
		TBD860073	Similar OECD 404	25	Irritating
		3108	Similar OECD 404	28	Not irritating
		2976	Similar OECD 404	70	Irritating
		000504/1	Similar OECD 404	68	Irritating
		3116	Similar OECD 404	1	Not irritating
		R9400325	OECD 404	70.1	Corrosive
		256/8409	Similar OECD 404	70	Irritating
		R9600430	OECD 404	27	Irritating
		86498D/UGF 17/SE	Similar OECD 404	70	Irritating
		Hoe88.0919	Similar OECD 404	69	Irritating
174450-50-1 / 605-725-1	Alcohols C12-14 (even numbered), ethoxylated (< 2.5 EO), sulphated, triisopropanolamine salts	2397	OECD 404	83.8	Irritating

 

Evaluation of skin irritation / corrosion as observed in studies

The concentration of AES substances in the test materials used in the skin irritation / corrosion studies varies from 1% to approx. 100%. Tested AES substances induced mostly moderate to severe erythema and oedema at concentrations above 25%. Irritation symptoms started to occur immediately after removal of the test substance and were usually reversible within the 21-day observation period of the respective studies. However, since in some studies observations were made for a period less than the maximum of 21 days, skin effects were still observed at the termination of most of these studies. AES concentrations ≤ 10% did not cause irritation (studies 4299 and 4306 with alcohols C10-16, ethoxylated (1-2,5 EO) sulphated, sodium salts, CAS No. 68585-34-2, EC No. 500-223-8). The only exception to this finding was one of the in vivo studies with alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8, study No. 3108) in which the substance was tested at a concentration of 28% and induced only very weak erythema which was fully reversible within the 8-day observation period. No oedema was observed in this study. The reason for this deviation from the general observation is unknown. In some studies, the exposure period was 24 h and/or an occlusive cover was used. Only one of the available studies revealed a corrosive potential (study no. R9400325 performed with alcohols, C12-14, ethoxylated, sulfates, sodium salts. All other available studies indicate a potential to induce irritation. The reason for the corrosion found in study R9400325 is unknown. However, since it is the only study in the database of the category, it is considered not to contradict the overall conclusion of skin irritation for AES substances. The main findings of the in vivo studies are supported by the available in vitro assays performed with alcohols, C8-10, ethoxylated, sulfates, sodium salts (CAS No. 1471312-55-6, EC No. 939-523-2). The combined results of the in vitro studies provide evidence for an irritating (but not corrosive) potential.

The WoE analysis based on the in vitro and in vivo studies indicates that AES substances in general exhibit a potential to induce skin irritation. This finding applies to all AES substances in the category, whether they belong to the ‘linear’, ‘unsaturated’ or ‘mixed branched & linear’ subgroups and it is fully supported by the OECD QSAR Toolbox profiling. The outcome of this overall WoE evaluation is used for the hazard assessment and to conclude on classification and labelling of all AES substances in the category. This evaluation is considered sufficient for the hazard assessment and classification and labelling of the AES substances. For a detailed evaluation of the skin irritation / corrosion potential of the substances in the AES category, please refer to the category justification attached to the category object.

 

Eye irritation

No data on eye irritation potential are available for alcohols, C9-11, branched and linear, ethoxylated, sulfates, sodium salts (CAS No. 160901-28-0, EC No. 500-465-4). In order to assess eye irritation, studies in the database of the AES category are considered in a read-across approach. Studies investigating eye irritation are available for the following AES substances:

 

Table 2: Database on eye irritation in the Alkyl Ether Sulfates (AES) category

CAS / EC Nos.	Substance	Study or Report No.	Study protocol (adopted in)	Concentration in test material [%]	Hazard conclusion based on study report
‘Linear’ subgroup
68585-34-2 / 500-223-8	Alcohols C10-16, ethoxylated (1-2,5 EO) sulphated, sodium salts	4298	Similar OECD 405	10	Serious eye damage
		97/10197-2	OECD 405	27	Not irritating
		RE80/159A	Similar OECD 405	58	Irritating
		28366	Similar OECD 405	69	Irritating
		4288	Similar OECD 405	25	Irritating
		4307	Similar OECD 405	24.3	Irritating
		4308	Similar OECD 405	1	Not irritating
		A/E/12323	Similar OECD 405	70	Not irritating
		97/9690-2	OECD 405	27	Irritating
		82-003C	Similar OECD 405	25 - 30	Irritating
		82-003F	Similar OECD 405	Not specified	Irritating
		19970	OECD 405	60	Serious eye damage
68891-38-3 / 500-234-8	Alcohols, C12-14, ethoxylated, sulfates, sodium salts	TBD890310	OECD 405	25	Serious eye damage
		3109	Similar OECD 405	28	Serious eye damage
		3117	Similar OECD 405	1	Not irritating
		261/8409	Similar OECD 405	70	Irritating
		Hoe88.1081	OECD 405	70	Serious eye damage
		R9600431	OECD 405	27 - 28	Irritating
		R9900359	OECD 405	27 - 28	Irritating
		97/10197-2	OECD 405	5.4	Not irritating
174450-50-1 / 605-725-1	Alcohols C12-14 (even numbered), ethoxylated (< 2.5 EO), sulphated, triisopropanolamine salts	2398	OECD 405	83	Serious eye damage

 

Evaluation of eye irritation as observed in studies

The concentration of AES substances in the tested materials ranges from 1% in the studies with alcohols C10-16, ethoxylated (1-2,5 EO) sulphated, sodium salts (CAS No. 68585-34-2, EC No. 500-223-8) and alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8) to 83% applied in the study with alcohols C12-14 (even numbered), ethoxylated (< 2.5 EO), sulphated, triisopropanolamine salts (CAS No. 174450-50-1, EC No. 605-725-1). Most of the studies were performed with AES concentrations between 25% and 70%. Concentrations at or above 10% generally induce moderate to severe irritant responses in conjunctiva, iris and cornea and cause chemosis. Some studies were terminated while effects were still observed in one or several animals. Since the observation periods applied in the different studies were not always as defined in the current OECD guideline 405, a concluding evaluation with respect to the reversibility of effects could not always be made and a case-by-case evaluation was made to reach a hazard conclusion. The exceptions to the general finding of irritating / damaging properties at concentrations > 10% are the studies 97/10197-2 and A/E/12323 with alcohols C10-16, ethoxylated (1-2,5 EO) sulphated, sodium salts (CAS No. 68585-34-2, EC No. 500-223-8). These studies resulted in ‘not irritating’ at concentrations of 27% and 70%, respectively. The reason for the deviation of the general irritating / damaging properties is not known. However, the studies contribute only to a minor extent to the hazard assessment of the whole AES category.

In the following studies severe eye damage was observed: 4298 (10% concentration) and 19970 (60% concentration) with alcohols C10-16, ethoxylated (1-2,5 EO) sulphated, sodium salts (CAS No. 68585-34-2, EC No. 500-223-8), as well as TBD890310, 3109, and Hoe88.1081 with alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8) at concentrations of 25%, 28%, and 70%, respectively. There is no clear trend in the available data between the concentration of a substance and the severity of eye effects (measured as chemosis, and reaction in conjunctivae, cornea, and iris) and it is therefore not possible to predict when eye irritation turns into serious eye damage. Therefore, all AES substances at concentrations ≥ 10% are considered to induce serious eye damage. The studies 4308 with alcohols C10-16, ethoxylated (1-2,5 EO) sulphated, sodium salts (CAS No. 68585-34-2, EC No. 500-223-8) and 3117 with alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8) clearly demonstrate that highly diluted AES substances are not irritating anymore. Based on the fact that most of the available studies revealed an eye irritating rather than an eye damaging potential and that the lowest concentration inducing eye damage is 25%, it is considered justifiable to define a cut-off concentration for eye damage of 10%. Therefore, a cut-off value for the induction of severe eye damage is set at a concentration of ≥ 10% for all AES substances in the category. The cut-off value for inducing irritation is set at a concentration of ≥ 5%.

In conclusion, the WoE analysis based on all available studies on eye irritation indicates that AES substances generally exhibit a potential to induce severe eye damage at concentration ≥ 10%, eye irritation in the concentration range 5 - 10% and no irritation < 5%. This finding applies to all AES substances in the category, whether they belong to the ‘linear’, ‘unsaturated’ or ‘mixed branched & linear’ subgroups and it is fully supported by the OECD QSAR Toolbox profiling. The outcome of this overall WoE evaluation is used for the hazard assessment and to conclude on classification and labelling for all AES substances in the category. This evaluation is considered sufficient for the hazard assessment and classification and labelling of the AES substances. For a detailed evaluation of the skin irritation / corrosion potential of the substances in the AES category, please refer to the category justification attached to the category object.

 

Data on counter ions

The counter ions Na⁺, Mg²⁺ and NH₄⁺ are not associated with an irritating or corrosive potential. They have no effect on the irritation / corrosion potential of the substances in the AES category.

In vivo studies on skin and eye irritation with alcohols C12-14 (even numbered), ethoxylated (< 2.5 EO), sulphated, triisopropanolamine salts (CAS No. 174450-50-1, EC No. 605-725-1) revealed an irritating and corrosive potential, respectively. Since skin irritation and eye damage have been identified for all members of the AES category - either based on experimental data or predicted for those AES substances lacking own data - the impact of triisopropanolamine (TIPA) has already been accounted for.

For a detailed evaluation of a potential effect of the counter ions on the toxicological profiles of the AES member substances, please refer to the category justification attached to the category object.

Justification for classification or non-classification

The available data on skin irritation with alcohols, C9-11, branched and linear, ethoxylated, sulfates, sodium salts (CAS No. 160901-28-0, EC No. 500-465-4) as well as with several member substances of the Alkyl Ether Sulfate (AES) category meet the criteria for classification according to the CLP Regulation (EC) No. 1272/2008 as Skin Irrit. 2, H315.

 

With respect to eye irritation, the available data with members of the AES category meet the criteria for classification according to the CLP Regulation. Based on grouping of substances (category approach), alcohols, C9-11, branched and linear, ethoxylated, sulfates, sodium salts (CAS No. 160901-28-0, EC No. 500-465-4) is predicted to fulfil the classification criteria and is classified as Eye Damage 1, H318.