Alcohols, C16-18 and C18-unsatd., ethoxylated

Endpoint summary

Description of key information

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

Conclusion based on data obtained with alcohols, C16-18 and C18-unsatd., ethoxylated (CAS No. 68920-66-1, EC No. 500-236-9) and considering all available data on skin irritation / corrosion in the Alcohol Ethoxylates (AE) category for substances containing unsaturated constituents in a Weight-of-Evidence approach.

Eye irritation (in vivo, rabbit, OECD 405): not irritating

Conclusion based on data obtained with alcohols, C16-18 and C18-unsatd., ethoxylated (CAS No. 68920-66-1, EC No. 500-236-9) 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:

02 - 24 Dec 1996

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted in 1992

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted in 2015

Deviations:

yes

Remarks:

no stepwise testing performed, age of the animals not reported, scoring according to Draize was reported until reading time point 72 h only although effects were observed up to the 14 day reading

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

adopted in 1992

GLP compliance:

yes

Species:

rabbit

Strain:

other: Mol:Russian

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Møllegaard Breeding and Research Centre, Ejby, Lille Skensved, Denmark
- Weight at study initiation: 2.2 – 2.5 kg
- Housing: Individually, in PPO cages (floor area 2576 cm^2) with perflorated floor
- Diet: Altromin 2123 (Altromin, Lage, Germany), ad libitum
- Water: Drinking water acidified with hydrochloric acid (to pH 2.5), ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3 °C
- Humidity (%): 55 ± 15
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

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:

21 days
Reading time points: 1, 24, 48 and 72 h and 7, 14 and 21 days

Number of animals:

3 females

Details on study design:

TEST SITE
- Area of exposure: A clipped area on the back of the animals of 10 x 10 cm. The clipped area was divided into four fields, the two posterior fields were used for testing. The test item was applied on two 2.5 x 2.5 cm 16-layer gauze patches and placed on the test site.
- Type of wrap if used: The gauze patches were secured with 2.5 cm wide adhesive tape and fixed with Micropore tape, 5cm width, loosely wound round the trunk.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treated skin was cleaned with mild soap and lukewarm water.
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS : 1, 24, 48 and 72 h and 7, 14 and 21 days

SCORING SYSTEM: Draize scoring

Irritation parameter:

erythema score

Basis:

animal: #1, #2 and #3

Time point:

24/48/72 h

Score:

2.3

Max. score:

4

Reversibility:

fully reversible within: 21 days

Irritation parameter:

edema score

Basis:

animal: #1 and #3

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 21 days

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 21 days

Irritant / corrosive response data:

Skin reactions were observed from the 24-hour reading onwards in all animals. At the 24 h reading, all animals showed slight erythema (score 1) and 1/3 animals showed slight edema (score 1). At the 48 and 72 h readings, 3/3 animals showed moderate to severe erythema (score 3) and slight edema (score 2). 7 days after application of the test article, all animals showed massive scab formation on the test areas. On study Day 14, 2/3 animals showed larger residues of scales on both test areas, 1/3 animals showed slight redness and residues of scales on both test areas and in 2/3 animals shiny skin was observed. 21 days after administration, all animals were free of lesions and showed complete hair and intact skin.

Table 1: Results on skin irritation for individual animals: erythema scores

Rabbit	Test field	Erythema
		1 h	24 h	48 h	72 h	Mean 24/48/72 h
1	left	0	1	3	3	2.33
	right	0	1	3	3
2	left	0	1	3	3	2.33
	right	0	1	3	3
3	left	0	1	3	3	2.33
	right	0	1	3	3

Table 2: Results on skin irritation for individual animals: edema scores

Rabbit	Edema
		1 h	24 h	48 h	72 h	Mean 24/48/72 h
1	left	0	0	2	2	1.33
	right	0	0	2	2
2	left	0	1	2	2	1.67
	right	0	1	2	2
3	left	0	0	2	2	1.33
	right	0	0	2	2

Interpretation of results:

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

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

02 - 21 Apr 2008

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted in 2002

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted in 2015

Deviations:

yes

Remarks:

no stepwise testing performed, no conclusion on irritation provided in study report, study terminated after 14 days although scales were still observed in 2/3 animals

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

adopted in 2004

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan, Horst, The Netherlands
- Age at study initiation: 13 weeks (male) and 12 weeks (female)
- Weight at study initiation: 2.26 - 2.42 kg
- Housing: Individually, in stainless steel cages with wood blocks and haysticks for gnawing
- Diet: Provimi Kliba 3418 rabbit maintainance diet (Provimi Kliba, Kaiseraugst, Switzerland), ad libitum
- Water: Tap water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23
- Humidity (%): 30 - 70
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 02 Apr 2008 To: 21 Apr 2008

Type of coverage:

semiocclusive

Preparation of test site:

clipped

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:

14 days
Reading time points: 1, 24, 48 and 72 h and 7, 10 and 14 days

Number of animals:

3 (1 male and 2 female)

Details on study design:

TEST SITE
- Area of exposure: On the left flank, an area of approx. 10 x 10 cm was clipped. The test material was applied to a surgical gauze patch (ca. 2.5 x 2.5 cm) and applied to the intact skin of the clipped area.
- Type of wrap if used: The patch was covered with a semi-occlussive dressing. The dressing was wrapped around the abdomen and anchored with tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The skin was flushed with lukewarm tap water.
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS : 1, 24, 48 and 72 h and 7, 10 and 14 days

SCORING SYSTEM: Draize scoring

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

animal: #2 and #3

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

animal: #1, #2 and #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

At 1 and 24 h after patch removal, well defined erythema (score 2) and a slight swelling (edema score 1) were observed in all 3 animals. At the 48 h reading, 1/3 animals still showed well defined erythema (score 2) and 2/3 of the animals showed slight erythema (score 1). Edema was no longer observed in the animals. At the 72 h reading, all 3 animals showed slight erythema (score 1) and scaling of the skin. At the later reading time points (7, 10 and 14 days), all animals were free from erythema. Scaling of the skin was observed in all 3 animals at the 7 and 10 day reading and persisted in 2/3 rabbits until termination on Day 14.

Other effects:

Systemic toxicity:
No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occured. The body weights of all rabbits were considered to be within the normal range of variability.

Table 1: Results on skin irritation for individual animals

Rabbit	Erythema			Edema			Scalling
	1	2	3	1	2	3	1	2	3
Sex	male	female	female	male	female	female	male	female	female
1 h	2	2	2	1	1	1	0	0	0
24 h	2	2	2	1	1	1	0	0	0
48 h	2	1	1	0	0	0	0	0	0
72 h	1	1	1	0	0	0	x	x	x
7 days	0	0	0	0	0	0	x	x	x
10 days	0	0	0	0	0	0	x	x	x
14 days	0	0	0	0	0	0	0	x	x
Mean 24/48/72 h	1.67	1.33	1.33	0.33	0.33	0.33

Interpretation of results:

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

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

16 - 24 Apr 2008

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted in 2002

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted in 2020

Deviations:

yes

Remarks:

no stepwise testing, no treatment with systemic analgesic/ topical anaesthesia of the animals / animal eyes

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

adopted in 2004

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Harlan, Horst, The Netherlands
- Age at study initiation: 13 weeks
- Weight at study initiation: 2.28 - 2.70 kg
- Housing: Individually, in stainless steel cages with wood blocks and haysticks for gnawing
- Diet: Provimi Kliba 3418 rabbit maintainance diet (Provimi Kliba, Kaiseraugst, Switzerland), ad libitum
- Water: Tap water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23
- Humidity (%): 30 - 70
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 16 Apr 2008 To: 24 Apr 2008

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 mL

Duration of treatment / exposure:

single administration without washing

Observation period (in vivo):

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

Number of animals or in vitro replicates:

3 (1 male, 2 female)

Details on study design:

SCORING SYSTEM: Draize scoring

TOOL USED TO ASSESS SCORE: Eye examinations were made with a Varta Cliptrix diagnostic-lamp (Roth AG, Reinach, Switzerland).

Irritation parameter:

cornea opacity score

Basis:

animal: #1, #2 and #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: 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: reversibility not applicable

Irritation parameter:

conjunctivae score

Basis:

animal: #1 and #2

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

animal: #1, #2 and #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritant / corrosive response data:

A slight to moderate reddening of the conjunctivae was noted in all animals (score 1 in 1/3 animals, score 2 in 2/3 animals) 1 hour after test item instillation and persisted as slight up to the 24- or 48 hour reading (sore 1 in 3/3 animals after 24 h and in 2/3 animals after 48 h).
In addition, a slight swelling (chemosis) of the conjunctivae as well as a slight reddening of the sclerae were observed in all 3 animals at the 1-hour reading. Slight ocular discharge was present in all animals at the same observation time point. No abnormal findings were observed in the treated eye of any animal 48 or 72 hours after treatment, the end of the observation period for all animals.
In addition, no abnormal findings were observed in the cornea or iris of any animal at any of the measurement intervals.

Other effects:

Systemic toxicity:
No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occured. The body weights of all rabbits were considered to be within the normal range of variability.

Table 1: Eye irritation results

Rabbit	Corneal opacity			Iris			Conjunctival redness			Conjunctival chemosis			Sclera
	1	2	3	1	2	3	1	2	3	1	2	3	1	2	3
1 h	0	0	0	0	0	0	2	1	2	1	1	1	1	1	1
24 h	0	0	0	0	0	0	1	1	1	0	0	0	0	1	0
48 h	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0
72 h	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Mean 24/48/72 h	0	0	0	0	0	0	0.67	0.67	0.33	0	0	0

Interpretation of results:

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

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

14 - 23 Oct 1996

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted in 1987

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted in 2020

Deviations:

yes

Remarks:

no stepwise testing, no treatment with systemic analgesic/ topical anaesthesia of the animals / animal eyes; scoring according to Draize reported until reading time point 72 h only although effects were observed up to Day 7

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

adopted in 1992

GLP compliance:

yes

Species:

rabbit

Strain:

other: Mol:Russian

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Møllegaard Breeding and Research Centre, Ejby, Lille Skensved, Denmark
- Weight at study initiation: 2.0 – 2.1 kg
- Housing: Individually, in PPO cages (floor area 2576 cm^2) with perflorated floor
- Diet: Altromin 2123 (Altromin, Lage, Germany), ad libitum
- Water: Drinking water acidified with hydrochloric acid (to pH 2.5), ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3 °C
- Humidity (%): 55 ± 15
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 mL

Duration of treatment / exposure:

single administration without washing

Observation period (in vivo):

7 days
Reading time points: 1, 24, 48 and 72 h and 7 days after test item instillation

Number of animals or in vitro replicates:

3 females

Details on study design:

SCORING SYSTEM: Draize scoring

TOOL USED TO ASSESS SCORE: fluorescein and UV light

Irritation parameter:

cornea opacity score

Basis:

animal: #1, #2 and #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: 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: reversibiity not applicable

Irritation parameter:

conjunctivae score

Basis:

animal: #1 and #2

Time point:

24/48/72 h

Score:

1.67

Max. score:

3

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

One hour after test item instillation, 2/3 rabbits showed diffuse redness (score 2) and 1/3 animals showed slight redness (score 1) of the conjunctiva. In addition, 2/3 animals showed an obvious swelling of the conjunctiva (score 2) while the third rabbit showed a slight swelling (score 1). Additionally, discharge with moistening of lids and hiars just adjacent to lids was observed in 2/3 animals.
At the 24 and 48 h readings, 2/3 animals showed diffuse redness (score 2) and obvious swelling (score 2) of the conjunctiva, while the last animal showed only slight redness (score 1) and swelling (score 1) of the conjunctiva.
72 h after administration of the test item, slight redness of the conjunctiva (score 1) was observed in all 3 rabbits, obvious swelling of the conjunctiva (score 2) was noted in 1/3 animals and slight swelling of the conjunctiva was observed in 2/3 animals.
At the day 7 reading, no signs of eye irritation were observed. However, the outer side of the lower lid in all 3 animals contained dried crusts with hairs, which could be removed from the lids.

Table 1: Eye irritation results

Rabbit	Corneal opacity			Iris			Conjunctival redness			Conjunctival chemosis			Conjunctival discharge
	1	2	3	1	2	3	1	2	3	1	2	3	1	2	3
1 h	0	0	0	0	0	0	2	2	1	1	2	2	0	2	2
24 h	0	0	0	0	0	0	2	2	1	2	2	1	0	0	0
48 h	0	0	0	0	0	0	2	2	1	2	2	1	0	0	0
72 h	0	0	0	0	0	0	1	1	1	2	1	1	0	0	0
Mean 24/48/72 h	0	0	0	0	0	0	1.67	1.67	1.00	2.00	1.67	1.00

Interpretation of results:

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

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 and C18-unsatd., ethoxylated (CAS No. 68920-66-1, EC No. 500-236-9) as well as several member substances of the Alcohol Ethoxylates (AE) category.

 

Studies with alcohols, C16-18 and C18-unsatd., ethoxylated (CAS No. 68920-66-1, EC No. 500-236-9)

The skin irritation potential of alcohols, C16-18 and C18-unsatd., ethoxylated (CAS No. 68920-66-1, EC No. 500-236-9) was investigated in a first in vivo study performed according to OECD guideline 404 under GLP conditions (BASF, 1997). 0.5 mL of the undiluted test substances was applied for 4 h to the shaved skin of three female albino rabbits under semi-occlusive conditions. 24 h after termination of exposure all animals showed a very slight erythema and after 48 and 72 h moderate to severe erythema as well as slight oedema was observed in all animals. 7 days after application the test areas of all animals showed a closed massive scab and 14 days after application two animals showed larger residues of scales while the third animal exhibited slight redness and residues of scales. Moreover, shiny skin was observed in two animals. All effects were reversed 21 days after exposure. All animals showed complete hair growth and intact skin. The mean individual erythema (oedema) scores were 2.33 (1.33), 2.33 (1.67), 2.33 (1.33), respectively. Based on the findings of the study, the test substance is irritating to skin and needs to be classified as Skin Irrit. 2, H315.

The primary skin irritation potential of alcohols, C16-18 and C18-unsatd., ethoxylated (CAS No. 68920-66-1, EC No. 500-236-9) was investigated in a second study according to OECD guideline 404 observing GLP conditions (Clariant, 2008a). The test item was applied by topical semi-occlusive application of 0.5 mL to the intact left flank of each of three young adult New Zealand White rabbits. The duration of treatment was 4 h. The scoring of skin reactions was performed 1, 24, 48 and 72 h, as well as 7, 10 and 14 days after removal of the dressing. The mean score was calculated across 3 scoring times (24, 48 and 72 h after patch removal) for each animal for erythema/eschar grades and for oedema grades, separately. The mean erythema/eschar score of the three animals was 1.67, 1.33 and 1.33, respectively and the mean oedema score was 0.33 for each of the three animals. The application of the test substance to the skin resulted in mild to moderate signs of irritation. These included erythema, oedema and scaling. These effects were reversible and were no longer evident 10 days after treatment in the male. However, in both females scaling was present up to day 14, the end of observation period. The test item caused no staining of the treated skin. No corrosive effects were noted on the treated skin of any animal at any of the measuring intervals and no clinical signs were observed.

 

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 and C18-unsatd., ethoxylated (CAS No. 68920-66-1, EC No. 500-236-9) as well as several member substances of the AE category.

 

Studies with alcohols, C16-18 and C18-unsatd., ethoxylated (CAS No. 68920-66-1, EC No. 500-236-9)

The eye irritating potential of alcohols, C16-18 and C18-unsatd., ethoxylated (CAS No. 68920-66-1, EC No. 500-236-9) was tested according to OECD guideline 405 under GLP conditions (BASF, 1996). Three female albino rabbits were exposed to 0.1 mL of the test substance. The unchanged test substance was applied to the left eye of each animal whereas the untreated eye served as negative control. The eyes were examined and the changes were graded 1, 24, 48 and 72 h as well as 7 days after dosing. Slight to moderate signs of irritation were observed in the rabbits. The following mean scores, based on the results of the 24, 48 and 72 h readings, were observed:

-       corneal opacity: 0, 0, 0 for animals #1, #2, #3, respectively

-       iris: 0, 0, 0 for animals #1, #2, #3, respectively

-       conjunctivae: 1.67, 1.67, 1 for animals #1, #2, #3, respectively

-       chemosis: 2, 1.67, 1 for animals #1, #2, #3, respectively

All effects were fully reversible within 7 days after application. The test substance is considered not irritating based on the findings of this study.

The results of the first study are fully supported by a second investigation of the eye irritation potential of alcohols, C16-18 and C18-unsatd., ethoxylated (CAS No. 68920-66-1, EC No. 500-236-9). The study was conducted according to OECD guideline 405 under GLP conditions. The test item was applied by instillation of 0.1 mL into the left eye of each of three young adult New Zealand White rabbits. Scoring of irritation effects was performed approx. 1, 24, 48 and 72 h after test item instillation. The mean score was calculated across 3 scoring times (24, 48 and 72 h after instillation) for each animal for corneal opacity, iris, redness and chemosis of the conjunctivae, separately. The individual mean scores for corneal opacity and iris were 0.00 for all three animals. The individual mean scores for the conjunctivae were 0.67, 0.67 and 0.33 for reddening and 0.00 for chemosis for each of the three animals. The instillation of the test substance resulted in mild, early-onset and transient ocular changes, such as reddening of the conjunctivae and sclerae, discharge and chemosis. These effects were reversible and were no longer evident 48 or 72 h after treatment. No abnormal findings were observed in the cornea or iris of any animal at any of the examinations. No corrosion was observed at any of the measuring intervals. No staining of the treated eyes by the test item was observed and no clinical signs were observed. Thus, the test item did not induce significant or irreversible damage to the rabbit 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 irritation obtained with alcohols, C16-18 and C18-unsatd., ethoxylated (CAS No. 68920-66-1, EC No. 500-236-9) and other members of the Alcohol Ethoxylates (AE) category containing unsaturated constituents meet the criteria for classification according to the CLP Regulation (EC) No. 1272/2008. The substance is therefore classified as Skin Irrit. 2, H315.

With respect to eye irritation, the available data on alcohols, C16-18 and C18-unsatd., ethoxylated (CAS No. 68920-66-1, EC No. 500-236-9) and with members of the AE category with carbon-chain lengths ≥ C12 do not meet the criteria for classification according to the CLP Regulation and are therefore conclusive but not sufficient for classification.