Alcohols, C12-15, ethoxylated

Endpoint summary

Description of key information

Skin irritation / corrosion (in vivo, rabbit, similar OECD 404): not irritating

Conclusion based on data obtained with alcohols, C12-15, branched and linear, ethoxylated (CAS No. 106232-83-1, EC No. 500-294-5) and considering all available data on skin irritation / corrosion in the Alcohol Ethoxylates (AE) category for substances containing only saturated constituents in a Weight-of-Evidence approach.

Eye irritation: not irritating

Read-across based on grouping of substances (category approach) considering all available data on eye irritation in the AE category for substances with carbon-chain lengths = C12 in a Weight-of-Evidence approach.

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:

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:

erythema score

Time point:

24/48/72 h

Remarks on result:

other: Not irritating based on all available skin irritation data in the Alcohol Ethoxylates (AE) category for substances containing only saturated constituents.

Irritation parameter:

edema score

Time point:

24/48/72 h

Remarks on result:

other: Not irritating based on all available skin irritation data in the Alcohol Ethoxylates (AE) category for substances containing only saturated constituents.

For a detailed assessment of the skin irritation / corrosion potential of the Alcohol Ethoxylates (AE) category, please refer to the category justification attached to the category object.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

Applying read-across based on grouping of substances (category approach), no skin irritating potential is predicted for the target substance.

Executive summary:

The available data on skin irritation / corrosion in the Alcohol Ethoxylates (AE) category indicate no 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 AE category are unlikely to lead to differences in the skin irritation / corrosion potential.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

Oct 1976

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)

Version / remarks:

adopted in 2015

Deviations:

yes

Remarks:

24 h exposure; occlusive dressing; 48 h-scoring is missing, no stepwise approach, study was terminated after 72 h although skin reactions were not reversible

GLP compliance:

no

Species:

rabbit

Strain:

other: Albino

Details on test animals or test system and environmental conditions:

No data

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

not specified

Controls:

not required

Duration of treatment / exposure:

24 h

Observation period:

72 h
Reading time points: 24 and 72 h

Number of animals:

3

Details on study design:

TEST SITE
- Type of wrap if used: The test material was applied to a square patch of surgical gauze measuring 1 inch x 1 inch and fixed with adhesive tape. The entire trunk of the animal was then wrapped with an impervious material such as subberised cloth for 24 h.

REMOVAL OF TEST SUBSTANCE
not specified

OBSERVATION TIME POINTS
24 and 72 h

SCORING SYSTEM:
- Method of calculation: Draize scoring

Irritation parameter:

erythema score

Basis:

animal: #1 and #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Only intact skin values were used for calculation. no 48 h data are available; for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h)

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Only intact skin values were used for calculation. no 48 h data are available; for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h)

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Only intact skin values were used for calculation. no 48 h data are available; for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h)

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Only intact skin values were used for calculation. no 48 h data are available; for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h)

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Only intact skin values were used for calculation. no 48 h data are available; for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h)

Irritant / corrosive response data:

At the 24 h reading, all animals showed well defined erythema (score 2) at the intact skin area. In addition, 1/3 rabbits showed very slight oedema (score 1) and 1/3 rabbits showed slight oedema (score 2). No 48 h reading was performed. After 72 h, 2/3 rabbits showed well defined erythema (score 2) and 1/3 rabbits even showed moderate to severe erythema (score 3). Slight oedema (score 2) was noted in all 3 animals.

Table 1: Skin irritation results for intact skin

Rabbit	Reaction	24 h	72 h
1	Erythema	2	2
1	Oedema	0	2
2	Erythema	2	3
2	Oedema	1	2
3	Erythema	2	2
3	Oedema	2	2

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

Under the condition of this test classification is not justified.

Executive summary:

The classification of the study report 7062/139/77 is based on a very rigorous treatment of the animals with the test material. Exposure to the test material for 24-hours under occlusive conditions is significantly higher than under the current OECD 404 prescribed exposure of 4-hours under semi-occluded conditions. Higher exposures will likely result in more severe effects. Hence, the results from this study overestimate the irritation potential when assessed against new OECD 404 guidance criteria.       

The influence of prolonged and intensified test conditions can be seen by comparing the results of TLGR.0157.78 and SBGR-93189.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not 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: Not irritating based on all available eye irritation data in the Alcohol Ethoxylates (AE) category for substances with carbon-chain lengths = C12.

Irritation parameter:

iris score

Time point:

24/48/72 h

Remarks on result:

other: Not irritating based on all available eye irritation data in the Alcohol Ethoxylates (AE) category for substances with carbon-chain lengths = C12.

Irritation parameter:

conjunctivae score

Time point:

24/48/72 h

Remarks on result:

other: Not irritating based on all available eye irritation data in the Alcohol Ethoxylates (AE) category for substances with carbon-chain lengths = C12.

Irritation parameter:

chemosis score

Time point:

24/48/72 h

Remarks on result:

other: Not irritating based on all available eye irritation data in the Alcohol Ethoxylates (AE) category for substances with carbon-chain lengths = C12.

For a detailed assessment of the eye irritation potential of the Alcohol Ethoxylates (AE) category, please refer to the category justification attached to the category object.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

Applying read-across based on grouping of substances (category approach), no eye irritating potential is predicted for the target substance.

Executive summary:

The available data on eye irritation in the Alcohol Ethoxylates (AE) category indicate no eye 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 AE category are unlikely to lead to differences in the eye irritation potential.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation / corrosion

Data on skin irritation / corrosion are available for alcohols, C12-15, branched and linear, ethoxylated (CAS No. 106232-83-1, EC No. 500-294-5) as well as several member substances of the Alcohol Ethoxylates (AE) category.

 

Study with alcohols, C12-15, branched and linear, ethoxylated (CAS No. 106232-83-1, EC No. 500-294-5)

The skin irritation potential of alcohols, C12-15, branched and linear, ethoxylated (CAS No. 106232-83-1, EC No. 500-294-5) was investigated in vivo in a study similar to OECD guideline 404 (Huntingdon, 1977). The test substance was applied to the skin of three rabbits. Well—defined erythema with or without very slight to slight oedema was observed in all three animals at the 24 h reading. By the 72 h reading well—defined to moderate erythema with or without slight or moderate oedema was observed. Hyperkeratinisation of the skin was seen in one animal at the 72 h reading only. No 48 h reading was taken in this study. 48 h scorings were extrapolated to use the study for the hazard assessment based on current classification criteria according to the CLP Regulation (EC) No. 1272/2008. Based on the findings of this study, the test substance is considered not irritating to the skin. Since no 48 h reading was performed, this study is regarded only as supporting other in vivo studies available in the data pool of the AE category.

 

Studies in the AE category

Studies on skin irritation / corrosion are available for the following AE members:

 

CAS No.	EC No.	Substance	Study protocol	Hazard conclusion
27252-75-1	500-058-1	Octan-1-ol, ethoxylated	OECD 431	Corrosive
26183-52-8	500-046-6	Decan-1-ol, ethoxylated	OECD 404	Not irritating
68439-50-9	500-213-3	Alcohols, C12-14, ethoxylated	OECD 404	Severely irritating
68439-49-6	939-518-5	Alcohols, C16-18 (even numbered), ethoxylated, < 2.5 EO	OECD 404	Not irritating
68920-66-1	500-236-9	Alcohols, C16-18 and C18 unsatd., ethoxylated	OECD 404	Irritating
			OECD 404	Not irritating
9005-00-9	500-017-8	Octadecan-1-ol, ethoxylated	Similar OECD 404	Not irritating
66455-14-9	500-165-3	Alcohols, C12-13, ethoxylated	Similar OECD 404	Not irritating
160901-19-9	500-457-0	Alcohols, C12-13, branched and linear, ethoxylated	OECD 404	Not irritating
106232-83-1	500-294-5	Alcohols, C12-15, branched and linear, ethoxylated	Similar OECD 404	Not irritating

 

Evaluation of skin irritation / corrosion as observed in studies

Most of the available study results for AE substances with a carbon-chain length = C10 containing only fully saturated constituents indicate a generally low irritating potential. Oedema and erythema formation (if any) is slight to moderate and mean oedema and erythema scores are below the threshold for classification according to the criteria of the CLP Regulation (EC) No. 1272/2008. All skin reactions (if any) are fully reversible within the observation period of the respective study. The exception is the findings of the study with alcohols, C12-14, ethoxylated (CAS No. 68439-50-9, EC No. 500-213-3). The reason for the severely irritating result of the latter study might be the occlusive coverage applied in this study. Exposure to a test material under occlusive conditions is significantly higher than under semi-occlusive conditions which is the standard in the current OECD 404 test guideline. It is reasonable to assume that higher exposures will most likely result in more severe effects. Hence, the results of the study over predict the irritation potential of alcohols, C12-14, ethoxylated (CAS No. 68439-50-9, EC No. 500-213-3) when assessed against new OECD 404 criteria. Based on all available data on skin irritation / corrosion in the AE category, it is established that the study with alcohols, C12-14, ethoxylated (CAS No. 68439-50-9, EC No. 500-213-3) should be regarded as an outlier most probably related to methodological deviations. The study is not considered in the assessment of the skin irritation potential of the substances in the AE category. Furthermore, the length of the alkyl chain if = C10 does not exert any influence on the skin irritation potential of AE substances. Members of the AE category containing only saturated constituents are generally not irritating to skin, irrespective of their carbon-chain length if it is = C10.

This evaluation is considered sufficiently conclusive for the hazard assessment and classification and labelling of the AE substances. For a detailed evaluation of the skin irritation / corrosion potential of the substances in the AE category, please refer to the category justification attached to the category object.

 

Eye irritation

No data on eye irritation are available for alcohols, C12-15, branched and linear, ethoxylated (CAS No. 106232-83-1, EC No. 500-294-5). In order to assess eye irritation, studies in the database of the AE category are considered in a read-across approach. Studies investigating eye irritation are available for the following AE substances:

 

CAS No.	EC No.	Substance	Study protocol	Hazard conclusion
68439-50-9	500-213-3	Alcohols, C12-14, ethoxylated	OECD 405	Not irritating
			OECD 405	Serious eye damage
68439-49-6	939-518-5	Alcohols, C16-18 (even numbered), ethoxylated, < 2.5 EO	OECD 405	Not irritating
68920-66-1	500-236-9	Alcohols, C16-18 and C18 unsatd., ethoxylated	OECD 405	Not irritating
			OECD 405	Not irritating
9005-00-9	500-017-8	Octadecan-1-ol, ethoxylated	Similar OECD 405	Not irritating
			Similar OECD 405	Not irritating
66455-14-9	500-165-3	Alcohols, C12-13, ethoxylated	Similar OECD 405	Not irritating
160901-19-9	500-457-0	Alcohols, C12-13, branched and linear, ethoxylated	OECD 405	Not irritating

 

Evaluation of eye irritation as observed in studies

All available study results indicate a generally low irritation potential of the AE substances towards the eye. Effects observed (if any) on corneal opacity, iridial and conjunctival irritation as well as chemosis were mainly mild and fully reversible within the observation period of the respective study. The mean scores determined in the studies are below the threshold for classification according to the criteria of the CLP Regulation (EC) No. 1272/2008. Only one of the two studies performed with alcohols, C12-14, ethoxylated (CAS No. 68439-50-9, EC No. 500-213-3) resulted in irreversible effects indicating a potential to cause serious eye damage whereas in the other study no eye irritation was observed. However, in the study demonstrating corrosion only one animal was used and it is the only study, out of the nine available studies, contradicting the general trend within the AE category. Based on all available experimental data on eye irritation in the AE category, it is therefore concluded not to consider the single study on only one animal demonstrating a potential for serious eye damage. Excluding this study, it is established that the length of the alkyl chain and the presence of unsaturated constituents do not exert any influence on the eye irritation potential of AE substances. However, experimental data regarding eye irritation for category members with a carbon-chain length < C12 are not available. Therefore, the eye irritation potential of AE member substances is also assessed based on the CESIO recommendation for the harmonised classification and labelling of surfactants (CESIO: the European Committee of Organic Surfactants and their Intermediates; www.cesio.eu/index.php/policy-legislation/classification-labelling). The CESIO approach also considers AE substances which are not members of the AE category, thus increasing the database for assessing the eye irritation potential. In summary, adequate and reliable studies performed with category member substances (with = C12) in combination with the CESIO recommendation for AE member substances with < C12 allow to conclude that category member substances containing at least one constituent with alkyl chain lengths < C12 exhibit an eye irritation potential whereas AE substances containing only constituents with an alkyl chain length of = C12 are not irritating to the eye.

This evaluation is considered sufficiently conclusive for the hazard assessment and classification and labelling of the AE substances. For a detailed evaluation of the eye irritation potential of the substances in the AE category, please refer to the category justification attached to the category object.

Justification for classification or non-classification

The available data on skin and eye irritation obtained with alcohols, C12-15, branched and linear, ethoxylated (CAS No. 106232-83-1, EC No. 500-294-5) and with other members of the Alcohol Ethoxylates (AE) category containing only saturated constituents and carbon-chain lengths = C12 do not meet the criteria for classification according to the CLP Regulation (EC) No. 1272/2008 and are therefore conclusive but not sufficient for classification.