Alcohols, C16-18, ethoxylated

Endpoint summary

Description of key information

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

Conclusion based on data obtained with alcohols, C16-18 (even numbered), ethoxylated, < 2.5 EO (CAS No. 68439-49-6, EC No. 939-518-5) 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 (in vivo, rabbit, OECD 405): not irritating

Conclusion based on data obtained with the target substance alcohols, C16-18 (even numbered), ethoxylated, < 2.5 EO (CAS No. 68439-49-6, EC No. 939-518-5) 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:

04 - 18 Nov 1986

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted in 1981

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted in 2015

Deviations:

yes

Remarks:

occlusive dressing, no step-wise testing performed

GLP compliance:

no

Species:

rabbit

Strain:

Himalayan

Remarks:

Chbb-SPF

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. Karl Thomae GmbH, Biberach, Germany
- Weight at study initiation: 2.1 - 2.7 kg
- Housing: single housing in stainless steel cages
- Diet: K4 Alleindiät für Kaninchen , Ssniff Spezialfutter GmbH, Soest, Germany, ad libitum
- Water: Tap water, ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 1
- Humidity (%): 60 +/- 5
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 14 Nov To: 18 Nov 1986

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

4 h

Observation period:

14 days

Number of animals:

3 males

Details on study design:

TEST SITE
- Area of exposure: approx. 10 cm x 10 cm
- Type of wrap if used: The application site was covered by a gauze bandage and a polyethylene foil (approx. 6 cm x 6 cm). The bandage was fixed with a flexible wrap.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Remaining test substance was gently rinsed with lukewarm water.
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS: 1, 24, 48, 72 h and 6, 8, 10, 14 days

SCORING SYSTEM: Draize scoring scheme

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

erythema score

Basis:

animal: #2 and #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other:

Remarks:

Reversibility not applicable

Irritation parameter:

edema score

Basis:

mean

Remarks:

of all 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other:

Remarks:

Reversibility not applicable

Remarks on result:

other:

Remarks:

No edema formation observed in any animal at any observation time point.

Irritant / corrosive response data:

One hour after patch removal, very slight to well defined erythema was observed in all 3 animals. 2/3 animals were without skin reactions at any scoring time point thereafter, whereas very slight erythema (grade 1) was still observed in the third animal 6 days after treatment. On study Days 8 and 10, scabs were noted in this animal. There were no findings on oedema at any reading time point. At termination on study Day 14, all animals were free of skin lesions.

Table 1: Erythema scores during the 14 days observation period

Animal	1 h	24 h	48 h	72 h	6 days	8 days	10 days	14 days	Mean 24/48/72 h
1	1	1	x1	x1	x1	Sc	Sc	0	1.00
2	1	0	0	0	0	0	0	0	0.00
3	2	0	0	0	0	0	0	0	0.00
x: localised skin reaction; Sc: scabs

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 according 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

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

18 - 24 Nov 1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted in 1981

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted in 2020

Deviations:

yes

Remarks:

No treatment with systemic analgesic or topical anaesthesia of the animals / animal eyes prior, during or after test substance application

GLP compliance:

no

Species:

rabbit

Strain:

Himalayan

Remarks:

Chbb-SPF

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Dr. Karl Thomae GmbH, Biberach, Germany
- Weight at study initiation: 2.3 - 2.5 kg
- Housing: Individually, in stainless steel cages
- Diet: K4 Alleindiät für Kaninchen (Ssniff Spezialfutter GmbH, Soest, Germany); ad libitum
- Water: Tap water; ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 1
- Humidity (%): 60 ± 5
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

72 h

Observation period (in vivo):

6 days
Reading time points: 1, 24, 48 and 72 h and 6 days

Number of animals or in vitro replicates:

3 males

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): With lukewarm physiological NaCl solution
- Time after start of exposure: 72 h after application

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: hand-slit lamp and fluorescein

Irritation parameter:

cornea opacity score

Basis:

animal: #1, #2 and #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other:

Remarks:

Reversibility not applicable

Irritation parameter:

iris score

Basis:

animal: #1, #2 and #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other:

Remarks:

Reversibility not applicable

Irritation parameter:

conjunctivae score

Basis:

animal: #1, #2 and #3

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other:

Remarks:

Reversibility not applicable

Irritation parameter:

chemosis score

Basis:

animal: #1, #2 and #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other:

Remarks:

Reversibility not applicable

Irritant / corrosive response data:

There were no eye irritation reactions observed for any animal during the 6 days observation period.

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 according to OECD guideline 405.

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, C16-18 (even numbered), ethoxylated, < 2.5 EO (CAS No. 68439-49-6, EC No. 939-518-5) as well as several member substances of the Alcohol Ethoxylates (AE) category.

 

Study with alcohols, C16-18 (even numbered), ethoxylated, < 2.5 EO (CAS No. 68439-49-6, EC No. 939-518-5)

The skin irritation potential of alcohols, C16-18 (even numbered), ethoxylated, < 2.5 EO (CAS No. 68439-49-6, EC No. 939-518-5) was investigated according to OECD guideline 404 (Sasol, 1986b). Three albino rabbits (Kleine weiße Russen (Chbb-SPF)) were exposed for 4 h to 0.5 mL of the undiluted test substance under occlusive conditions. Approx. 24 h prior to application, the application sites were clipped. Remaining test substance was gently rinsed with lukewarm water. Skin reactions were observed 1, 24, 48 and 72 h as well as 6, 8, 10 and 14 days after application. One animal showed oedema (score 1) at the 24, 48 and 72 h reading points, which was fully reversible within the 14 days observation period. No further skin reactions (erythema or oedema) were observed in any other animal at any time point. The test substance was therefore evaluated to be 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 alcohols, C16-18 (even numbered), ethoxylated, < 2.5 EO (CAS No. 68439-49-6, EC No. 939-518-5) as well as several member substances of the AE category.

 

Study with alcohols, C16-18 (even numbered), ethoxylated, < 2.5 EO (CAS No. 68439-49-6, EC No. 939-518-5)

An in vivo study investigating the eye irritation potential of alcohols, C16-18 (even numbered), ethoxylated, < 2.5 EO (CAS No. 68439-49-6, EC No. 939-518-5) according to OECD guideline 405 is available (Sasol, 1986c). Three albino rabbits (Kleine weiße Russen (Chbb-SPF)) were treated with 0.1 mL of undiluted test substance for 72 h until the exposed eyes were washed with lukewarm physiological saline. Adverse reactions were scored according to the Draize 1, 24, 48 and 72 h as well as 6 days after application. No reactions were observed in any animal at any time point. Therefore, the study was terminated 6 days after application. Based on the lack of any adverse effects, the test substance is considered not irritating to the eye.

 

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 alcohols, C16-18 (even numbered), ethoxylated, < 2.5 EO (CAS No. 68439-49-6, EC No. 939-518-5) 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.