Octadecan-1-ol, ethoxylated

Endpoint summary

Description of key information

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

Conclusion based on data obtained with octadecan-1-ol, ethoxylated (CAS No. 9005-00-9, EC No. 500-017-8) 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 (in vivo, rabbit, similar OECD 405): not irritating

Conclusion based on data obtained with octadecan-1-ol, ethoxylated (CAS No. 9005-00-9, EC No. 500-017-8) and 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:

experimental study

Adequacy of study:

weight of evidence

Study period:

Nov 1975

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:

6 animals used, 24 h exposure; no 1 or 48 h reading, no stepwise testing performed, no information on animals or environmental conditions, limited reporting on procedure and results, no information on type of wrap used for patch fixation

GLP compliance:

no

Remarks:

Prior to implementation of GLP.

Species:

rabbit

Strain:

other: only "albino rabbit" reported

Details on test animals or test system and environmental conditions:

No data.

Type of coverage:

not specified

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

yes, concurrent no treatment

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

24 h

Observation period:

72 h
Reading time points: 24 and 72 h

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: The test material was applied to a shaved area on the back of the animals. Intact skin was exposed on the left half of the shaved area, abraded skin was exposed on the right half of the shaved area. The test material was introduced under a square patch of surgical gauze measuring 1 inch x 1 inch. Patches were removed 24 h after administration.
- Type of wrap if used: not specified

OBSERVATION TIME POINTS
24 and 72 h

SCORING SYSTEM:
- Method of calculation: Draize scoring

Irritation parameter:

erythema score

Basis:

animal: #1, #2, #3, #4, #5 and #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Remarks on result:

other: 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, #2, #3, #4, #5 and #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Remarks on result:

other: 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:

After test item administration to intact rabbit skin, no skin reactions were observed at any reading time point.
After test item administration to abraded rabbit skin, 2/6 animals showed very slight erythema (score 1) and 1/6 animals showed very slight oedema (score 1).

Table 1: Skin reactions after administration to intact and abraded skin

Parameter	Reading time point	Rabbit
		1	2	3	4	5	6
Erythema
Intact skin	24 h	0	0	0	0	0	0
	72 h	0	0	0	0	0	0
	mean 24/48/72h^#	0	0	0	0	0	0
Abraded skin	24 h	0	0	0	0	0	0
	72 h	1	0	1	0	0	0
	mean 24/48/72h^#	0.33	0	0.33	0	0	0
Oedema
Intact skin	24 h	0	0	0	0	0	0
	72 h	0	0	0	0	0	0
	mean 24/48/72h^#	0	0	0	0	0	0
Abraded skin	24 h	0	0	0	0	0	0
	72 h	0	0	1	0	0	0
	mean 24/48/72h^#	0	0	0.33	0	0	0
^#: 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)

Interpretation of results:

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

Conclusions:

The test substance did not induce skin irritation in an in vivo study similar to OECD guideline 404.

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: 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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye 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 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted in 2020

Deviations:

yes

Remarks:

please refer to "Principles of method if other than guideline" for details.

Principles of method if other than guideline:

Deviations to OECD guideline 405 (2020): 6 animals/sex used, no systemic analgesics and topical anaesthetics given, no stepwise testing, no information on animals or environmental conditions, limited reporting on procedure and results; conjunctival reactions not discriminated for redness and chemosis (only one value reported), 60% formulation used

GLP compliance:

no

Remarks:

Prior to implementation of GLP.

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 1.4 - 2.1 kg

Vehicle:

water

Remarks:

60% formulation

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

72 h

Observation period (in vivo):

14 days. However only data for 6 days were available.
Reading time points: 1, 24, 48, 72 and 96 h and 7, 10 and 14 days

Number of animals or in vitro replicates:

9 (6 male and 3 female)
6 animals (3 male and 3 female): no washing; 3 animals (3 male): eyes were rinsed after test item instillation

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Washing was perfomed in 6/9 animals using 20 mL of water at body temperature
- Time after start of exposure: 2 seconds after test item instillation

SCORING SYSTEM: Draize scoring

TOOL USED TO ASSESS SCORE: not specified

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

out of 6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Remarks on result:

other: Only unwashed animals were regarded for calculation.

Irritation parameter:

iris score

Basis:

mean

Remarks:

out of 6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility not applicable

Remarks on result:

other: Only unwashed animals were regarded for calculation.

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

out of 6 animals

Time point:

24/48/72 h

Score:

0.4

Max. score:

3

Reversibility:

fully reversible

Remarks on result:

other: Only unwashed animals were regarded for calculation. Score represents a worst case, since individual scores for conjunctivae and chemosis are not given.

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

out of 6 animals

Time point:

24/48/72 h

Score:

0.5

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: Only unwashed animals were regarded for calculation. Score represents a worst case, since individual scores for conjunctivae and chemosis are not given.

Irritant / corrosive response data:

The test item showed irritation in 3/6 unwashed eyes 24 h after instillation. In the remaining animals, no irritation was observed for any animal at any reading time point.

Interpretation of results:

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

Conclusions:

The test substance, applied at a concentration of 60% in water, did not induce eye irritation in an in vivo study similar to OECD guideline 405.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

Nov 1975

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 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted in 2020

Deviations:

yes

Remarks:

6 animals used, no systemic analgesics and topical anesthetics given, no stepwise testing, no 1-h reading; no information on animals or environmental conditions, limited reporting on procedure and results

GLP compliance:

no

Remarks:

Prior to implementation of GLP.

Species:

rabbit

Strain:

other: albino

Details on test animals or tissues and environmental conditions:

No data

Vehicle:

not specified

Controls:

yes, concurrent no treatment

Amount / concentration applied:

not specified

Duration of treatment / exposure:

single application without washing

Observation period (in vivo):

7 days
Reading time points: 24, 48 and 72 h and 7 days

Number of animals or in vitro replicates:

6

Details on study design:

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: not specified

Irritation parameter:

cornea opacity score

Basis:

animal: #1, #2, #3, #4, #5 and #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

iris score

Basis:

animal: #1, #2, #3, #4, #5 and #6

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility: not applicable

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

animal: #2, #3, #4, #5 and #6

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: reversibility: not applicable

Irritation parameter:

chemosis score

Basis:

animal: #1, #2, #3, #4, #5 and #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritant / corrosive response data:

One animal showed conjunctival redness (grade 1) at the 24, 48 and 72 h reading time point, which resolved within 7 days. No further reactions were noted in any of the animals.

Interpretation of results:

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

Conclusions:

The test substance did not induce eye irritation in an in vivo study similar to OECD guideline 405.

Reference 3

Endpoint:

eye 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:

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 octadecan-1-ol, ethoxylated (CAS No. 9005-00-9, EC No. 500-017-8) as well as several member substances of the Alcohol Ethoxylates (AE) category.

 

Study with octadecan-1-ol, ethoxylated (CAS No. 9005-00-9, EC No. 500-017-8)

A study comparable to OECD guideline 404 with octadecan-1-ol, ethoxylated (CAS No. 9005-00-9, EC No. 500-017-8) assessed the irritating potential to the skin (Food and Drug Research Laboratories, 1975b). Six albino rabbits were exposed for 24 h to 0.5 mL test substance under semi-occlusive conditions and observed for the following 72 h. Mean erythema and oedema scores over all animals within three days were 0. No 48 h score is 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). Based on the lack of any skin reactions, the test substance is consider not irritating to skin.

 

Studies in the AE category

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

 

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

Data on eye irritation are available for octadecan-1-ol, ethoxylated (CAS No. 9005-00-9, EC No. 500-017-8) as well as several member substances of the AE category.

 

Studies with octadecan-1-ol, ethoxylated (CAS No. 9005-00-9, EC No. 500-017-8)

An eye irritation study with octadecan-1-ol, ethoxylated (CAS No. 9005-00-9, EC No. 500-017-8) was performed with six albino rabbits similar to OECD guideline 405 (Food and Drug Research Laboratories, 1975c). The rabbits were treated with the test substance without washing. The eyes were examined 24, 48 and 72 h and 7 days after test substance application. One animal showed conjunctival redness (grade 1) at the 24, 48 and 72 h reading time point, which resolved within 7 days. No further reactions were noted in any of the animals. Thus the test material is not considered to be irritating to the eyes.

A further study assessing the eye irritating potential of octadecan-1-ol, ethoxylated (CAS No. 9005-00-9, EC No. 500-017-8) was performed similar to OECD guideline 405 (Atlas Chemical Industries, 1963) with New Zealand White rabbits. Six animals were treated with 0.1 mL of an aqueous solution of test item (concentration of test substance: 60%) and eye reactions were scored 1, 2, 3, 4, 7, 10 and 14 days after instillation. The mean 24, 48 and 72 h cornea, iris, conjunctivae and chemosis scores of six rabbits were 0, 0, 0.4 and 0.5, respectively. All effects were fully reversible. Therefore, aqueous solutions of 60% octadecan-1-ol, ethoxylated (CAS No. 9005-00-9, EC No. 500-017-8) were not eye irritating under the conditions of the study.

 

Studies in the AE category

Adequate and reliable studies on eye irritation are available for the following AE members:

 

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 octadecan-1-ol, ethoxylated (CAS No. 9005-00-9, EC No. 500-017-8) 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.