Alcohols, C12-13, branched and linear, 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, C12-13, branched and linear, ethoxylated (CAS No. 160901-19-9, EC No. 500-457-0) 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 alcohols, C12-13, branched and linear, ethoxylated (CAS No. 160901-19-9, EC No. 500-457-0) 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

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Mar 1984

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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:

6 animals used instead of 3, occlusive test conditions, no stepwise testing performed, results of first reading 30-60 min after patch removal not reported

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Breeding center Padre Antonio, Italy
- Weight at study initiation: 2 - 3 kg
- Housing: Stainless steel cages
- Diet: Pelleted complete diet (Nossan, Milano, Italy), ad libitum
- Water: Tap water from the local network, filtered with Seitz filter, ad libitum
- Acclimation period: one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 55 ± 15
- Air changes (per hr): at least 8
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 mL

Duration of treatment / exposure:

4 h

Observation period:

7 days

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure:approximately 6 square centimeters on the back of the animals
- Type of wrap if used: The test item was applied to a sterile gauze patch (hydrophilic, 12 layers surgial gauze, 2.5 x 2.5 cm). The impregnated gauze patch was kept in contact with the skin and secured in place by a thin band of adhesive hypoallergenic tape, 10 cm wide. The entire trunk was wrapped with rubberised cloth (Acrylastic Beyersdorf AG, Hamburg, Germany)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After patch removal, the test substance was cleaned out with water or an appropriate solvent.
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS: 30 - 60 min, 24, 48, 72 h and 5 and 7 days

SCORING SYSTEM: Draize scoring scheme

Irritation parameter:

erythema score

Basis:

animal: #1, #2 and #6

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

erythema score

Basis:

animal: #3, #4 and #5

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

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

Irritant / corrosive response data:

In 3/6 rabbits, very slight erythema (score 1) was observed at the 24 and 48 h reading. At the 72 h reading, there were no skin reactions observed in any animal. Oedema was not observed in any of the treated animals at any reading time point.

Table 1: Erythema scores observed in the individual animals

Animal	24 h	48 h	72 h	5 days	7 days	Mean 24/48/72 h
1	1	1	0	0	0	0.67
2	1	1	0	0	0	0.67
3	0	0	0	0	0	0.00
4	0	0	0	0	0	0.00
5	0	0	0	0	0	0.00
6	1	1	0	0	0	0.67

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.

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar 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:

6 animals used instead of 3; no treatment with systemic analgesic or topical anaesthesia of the animals / animal eyes prior, during or after test substance application

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Breeding center Padre Antonio, Italy
- Weight at study initiation: 2 - 3 kg
- Housing: In stainless steel cages type 1472 Tecniplast Gazzada VA, Italy
- Diet: Pelleted complete diet (Nossan, Milano, Italy), ad libitum
- Water: Tap water from the local network, filtered with Seitz filter, ad libitum
- Acclimation period: one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 55 ± 15
- Air changes (per hr): at least 8
- 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:

single instillation without washing

Observation period (in vivo):

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

Number of animals or in vitro replicates:

6

Details on study design:

SCORING SYSTEM:
Draize Scoring

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

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, #2 and #4

Time point:

24/48/72 h

Score:

1.67

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal: #3 and #5

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal #6

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

animal: #1, #2 and #3

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

animal: #4, #5 and #6

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritant / corrosive response data:

All animals showed conjunctival redness (scores 1 or 2) and conjunctival chemosis (scores 1 - 2) at the 1 and 24 h reading time point. At the 48 h reading, conjunctival redness (score 1) was observed in all 6 animals and conjunctival chemosis was noted in 3/6 animals. Corneal opacity or iritis findings were not observed at any reading time point. All eye irritation effects were fully reversible within 72 h post test item instillation.

Table 1: Individual scorings

Animal	1 h	24 h	48 h	72 h	7 days	Mean 24/48/72 h
Corneal opacity
1	0	0	0	0	0	0.00
2	0	0	0	0	0	0.00
3	0	0	0	0	0	0.00
4	0	0	0	0	0	0.00
5	0	0	0	0	0	0.00
6	0	0	0	0	0	0.00
Iris
1	0	0	0	0	0	0.00
2	0	0	0	0	0	0.00
3	0	0	0	0	0	0.00
4	0	0	0	0	0	0.00
5	0	0	0	0	0	0.00
6	0	0	0	0	0	0.00
Conjunctival redness
1	2	2	1	0	0	1.67
2	2	2	1	0	0	1.67
3	2	1	1	0	0	1.33
4	2	2	1	0	0	1.67
5	2	1	1	0	0	1.33
6	1	1	1	0	0	1.00
Conjunctival chemosis
1	2	1	1	0	0	0.67
2	2	1	1	0	0	0.67
3	1	1	1	0	0	0.67
4	2	1	0	0	0	0.33
5	1	1	0	0	0	0.33
6	1	1	0	0	0	0.33

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, C12-13, branched and linear, ethoxylated (CAS No. 160901-19-9, EC No. 500-457-0) as well as several member substances of the Alcohol Ethoxylates (AE) category.

 

Study with alcohols, C12-13, branched and linear, ethoxylated (CAS No. 160901-19-9, EC No. 500-457-0)

The skin irritating potential of alcohols, C12-13, branched and linear, ethoxylated (CAS No. 160901-19-9, EC No. 500-457-0) was investigated in a study similar to OECD guideline 404 (Sasol, 1984b). 0.5 mL of the unchanged test substance was applied to the shaved skin of six New Zealand White rabbits under occlusive conditions. The exposure period was 4 h and skin reactions were scored after 30-60 min, 24, 48, 72 h as well as after 5 and 7 days after termination of exposure. Grade 1 erythema was observed 24 and 48 h after termination of exposure in 3/6 animals resulting in a mean score for the 24/48/72 h readings of 0.67 for each of the three animals. The skin reactions were completely reversed at the 72 h reading. No further skin reactions (erythema or oedema) were observed in any animal at any reading time point. Based on the minimal 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 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 / serious eye damage

Data on eye irritation are available for alcohols, C12-13, branched and linear, ethoxylated (CAS No. 160901-19-9, EC No. 500-457-0) as well as several member substances of the AE category.

 

Study with alcohols, C12-13, branched and linear, ethoxylated (CAS No. 160901-19-9, EC No. 500-457-0)

The eye irritation potential of alcohols, C12-13, branched and linear, ethoxylated (CAS No. 160901-19-9, EC No. 500-457-0) was investigated in a study similar to OECD guideline 405 (Sasol, 1984c). 0.1 mL of the unchanged test substance was instilled in one of the eyes of six New Zealand White rabbits. The eyes were not washed after a certain period to stop the exposure. Eye reactions were scored according to the Draize scheme 1, 24, 48 and 72 h as well as 7 days after start of the exposure. The test substance induced conjunctival redness in all animals (grade 2 in 3/6 and grade 1 in 3/6 at the 24 h reading and score 1 in 6/6 animals at the 48 h reading), fully reversible within 72 h. In addition, chemosis (grade 1) was observed in all animals at the 24 h reading and in 3/6 animals at the 48 h reading, fully reversible within 72 h. No further eye reactions were observed in any animal at any observation time point. According to the findings of the study, the test substance is not considered to be irritating to the eye.

 

Studies in the AE category

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, C12-13, branched and linear, ethoxylated (CAS No. 160901-19-9, EC No. 500-457-0) 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.