C16-18 (evennumbered), C18 unsaturated alkylamine ethoxylated

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

September 1989 - January 1990

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Substance: CESIO 33. No data on batch no. and composition. Basic data given according to guidelines/standards.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

read-across: supporting information

Reference

Endpoint:

skin irritation: in vivo

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

September 1989 - January 1990

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Substance: CESIO 33. No data on batch no. and composition. Basic data given according to guidelines/standards.

Justification for type of information:

Data has been generated in a category approach, a justification for read across and the explanation of the category approach is available in Chapter 13.2.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

6 animals rather than 3 animals were used

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd., Moston, UK
- Age at study initiation: 12-16 weeks
- Weight at study initiation: 2-3 kg
- Housing: individually in suspended metal cages
- Diet (e.g. ad libitum): ad lib
- Water (e.g. ad libitum): ad lib
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 13-21
- Humidity (%): 47-69
- Air changes (per hr): ca. 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 26 September 1989 To: 4 January 1990 (for all 17 compounds)

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml

Duration of treatment / exposure:

4 hours (Exposure of 3 min was also preformed but no data reported).

Observation period:

up to 14 days

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm gauze patch
- % coverage: not indicated
- Type of wrap if used: gauze patch was secured with surgical adhesive tape (2.5 x 4 cm); the trunk was wrapped in an
elasticated corset.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, by gently swabbing with cotton wool soaked in diethyl ether
- Time after start of exposure: immediately following patch removal


SCORING SYSTEM:
EVALUATION OF SKIN REACTIONS
Erythema and eschar formation
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to slight eschar
formation (injuries in depth) 4

Oedema formation
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well-defined by
definite raising) 2
Moderate oedema (raised approximately 1 mm) 3
Severe oedema (raised more than 1 mm and
extending beyond area of exposure) 4

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.67

Max. score:

3

Reversibility:

not reversible

Remarks on result:

other: scar tissue

Remarks:

At 72 hrs unable to evaluate degree of erythema or oedema due to presence of other adverse dermal reactions

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other:

Remarks:

At 72 hrs unable to evaluate degree of erythema or oedema due to presence of other adverse dermal reactions

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not reversible

Remarks on result:

other:

Remarks:

At 72 hrs unable to evaluate degree of erythema or oedema due to presence of other adverse dermal reactions

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3.5

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other:

Remarks:

At 72 hrs unable to evaluate degree of erythema or oedema due to presence of other adverse dermal reactions

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not reversible

Remarks on result:

other:

Remarks:

From day 7 unable to evaluate degree of erythema or oedema due to presence of other adverse dermal reactions

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3.67

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other:

Remarks:

From day 7 unable to evaluate degree of erythema or oedema due to presence of other adverse dermal reactions

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not reversible

Remarks on result:

other:

Remarks:

From day 7 unable to evaluate degree of erythema or oedema due to presence of other adverse dermal reactions

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

3.67

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other:

Remarks:

From day 7 unable to evaluate degree of erythema or oedema due to presence of other adverse dermal reactions

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not reversible

Remarks on result:

other:

Remarks:

From day 7 unable to evaluate degree of erythema or oedema due to presence of other adverse dermal reactions

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

3.67

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other:

Remarks:

From day 7 unable to evaluate degree of erythema or oedema due to presence of other adverse dermal reactions

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

2.5

Max. score:

3

Reversibility:

not reversible

Remarks on result:

other:

Remarks:

From 72 hrs unable to evaluate degree of erythema or oedema due to presence of other adverse dermal reactions

Irritation parameter:

edema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

3.5

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other:

Remarks:

From 72 hrs unable to evaluate degree of erythema or oedema due to presence of other adverse dermal reactions

Irritant / corrosive response data:

Severe dermal responses were produced. The adverse skin reactions sometimes precluded accurate evaluation of erythema and
oedema. Very slight to well -defined erythema, haemorrhage of the dermal capillaries and slight to moderate oedema were noted
one hour after patch removal. The responses increased in severity and at subsequent observations were identified as well -
defined and moderate to severe oedema, haemorrhage of the dermal capillaries, blanching of the skin, a brown discolouration of theepidermis, scabbing, loss of skin flexibility, a straw-coloured crust (possible hyperkeratinisation), desquamation, thickening of the
skin, reduced re-growth of fur and glossy skin. Scar tissue, indicative of dermal corrosion was noted in five out of six rabbits.

Other effects:

No data.

Summary of dermal irritation (following 4-h application)

Animal no.	Effect	Hour	Days after application							Mean score erythema (24/48/72 h)	Mean score oedema (24/48/72 h)
		1	1	2	3	7	14
25 M	Erythema Oedema	2 2	3 4	2 4	? ?	? ?	? ?			2.5?	4?
28 F	Erythema Oedema	2 2	3 4	3 3	? ?	? ?	0 ?			3?	3.5?
31 M	Erythema Oedema	2 3	3 4	3 4	3 3	? ?	? ?			3	3.67
33 M	Erythema Oedema	2 2	3 4	3 4	3 3	? ?	? ?			3	3.67
73 M	Erythema Oedema	2 2	2 4	2 4	2 3	? ?	? 0			2	3.67
134 F	Erythema Oedema	1 2	2 4	3 3	? ?	? ?	? ?			2.5?	3.5?
Mean all animals										2.67?	3.67?

? Unable to evaluate degree of erythema or oedema due to presence of other adverse dermal reactions

At day 7: scabs, dry straw-coloured crust, sometimes flaking from the skin (possible hyperkeratinisation)

At day 14: desquamation, thickening of the skin, scabs, scar tissue, reduced re-growth of fur, skin glossy in appearance (keratinolysis)

Interpretation of results:

Category 1C (corrosive) based on GHS criteria

Remarks:

Migrated information

Conclusions:

The test material was considered to be corrosive (Category 1C) to the rabbit skin according to OECD-GHS. This was essentially
based on the formation of scar tissue, indicative of dermal corrosion, in 5 out of 6 rabbits.

Executive summary:

A study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method used followed the recommendations of the OECD Guidelines for Testing of Chemicals No. 404 "Acute Dermal Irritation/Corrosion" and Method B4 of the EC. A single

4 -hour, semi-occluded application of the test material to the intact skin of six rabbits produced severe dermal responses. Scar tissue, indicative of dermal corrosion was noted in 5 out of 6 rabbits 14 days after application. The test material was therefore classified as corrosive (Category 1C) to the rabbit skin, according to OECD/GHS criteria.

Cross-reference 2

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

6 animals rather than 3 animals were used

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2,2'-(C16-18 (evennumbered, C18 unsaturated) alkyl imino) diethanol

EC Number:

620-540-6

Cas Number:

1218787-32-6

Molecular formula:

No molecular formula

IUPAC Name:

2,2'-(C16-18 (evennumbered, C18 unsaturated) alkyl imino) diethanol

Test material form:

liquid

Details on test material:

- Chemical name: 2,2'-(C16-18 (evennumbered, C18 unsaturated) alkyl imino) diethanol
- EC number: 620-540-6

To the best of knowledge, the sample used is representative to the boundary composition shared and agreed by each registrant

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd., Moston, UK
- Age at study initiation: 12-16 weeks
- Weight at study initiation: 2-3 kg
- Housing: individually in suspended metal cages
- Diet (e.g. ad libitum): ad lib
- Water (e.g. ad libitum): ad lib
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 13-21
- Humidity (%): 47-69
- Air changes (per hr): ca. 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 26 September 1989 To: 4 January 1990 (for all 17 compounds)

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml

Duration of treatment / exposure:

4 hours (Exposure of 3 min was also preformed but no data reported).

Observation period:

up to 14 days

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm gauze patch
- % coverage: not indicated
- Type of wrap if used: gauze patch was secured with surgical adhesive tape (2.5 x 4 cm); the trunk was wrapped in an
elasticated corset.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, by gently swabbing with cotton wool soaked in diethyl ether
- Time after start of exposure: immediately following patch removal


SCORING SYSTEM:
EVALUATION OF SKIN REACTIONS
Erythema and eschar formation
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to slight eschar
formation (injuries in depth) 4

Oedema formation
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well-defined by
definite raising) 2
Moderate oedema (raised approximately 1 mm) 3
Severe oedema (raised more than 1 mm and
extending beyond area of exposure) 4

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.67

Max. score:

3

Reversibility:

not reversible

Remarks on result:

other: scar tissue

Remarks:

At 72 hrs unable to evaluate degree of erythema or oedema due to presence of other adverse dermal reactions

Results 2

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other:

Remarks:

At 72 hrs unable to evaluate degree of erythema or oedema due to presence of other adverse dermal reactions

Results 3

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not reversible

Remarks on result:

other:

Remarks:

At 72 hrs unable to evaluate degree of erythema or oedema due to presence of other adverse dermal reactions

Results 4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3.5

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other:

Remarks:

At 72 hrs unable to evaluate degree of erythema or oedema due to presence of other adverse dermal reactions

Results 5

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not reversible

Remarks on result:

other:

Remarks:

From day 7 unable to evaluate degree of erythema or oedema due to presence of other adverse dermal reactions

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3.67

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other:

Remarks:

From day 7 unable to evaluate degree of erythema or oedema due to presence of other adverse dermal reactions

Results 7

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not reversible

Remarks on result:

other:

Remarks:

From day 7 unable to evaluate degree of erythema or oedema due to presence of other adverse dermal reactions

Results 8

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

3.67

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other:

Remarks:

From day 7 unable to evaluate degree of erythema or oedema due to presence of other adverse dermal reactions

Results 9

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not reversible

Remarks on result:

other:

Remarks:

From day 7 unable to evaluate degree of erythema or oedema due to presence of other adverse dermal reactions

Results 10

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

3.67

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other:

Remarks:

From day 7 unable to evaluate degree of erythema or oedema due to presence of other adverse dermal reactions

Results 11

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

2.5

Max. score:

3

Reversibility:

not reversible

Remarks on result:

other:

Remarks:

From 72 hrs unable to evaluate degree of erythema or oedema due to presence of other adverse dermal reactions

Results 12

Irritation parameter:

edema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

3.5

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other:

Remarks:

From 72 hrs unable to evaluate degree of erythema or oedema due to presence of other adverse dermal reactions

Irritant / corrosive response data:

Severe dermal responses were produced. The adverse skin reactions sometimes precluded accurate evaluation of erythema and
oedema. Very slight to well -defined erythema, haemorrhage of the dermal capillaries and slight to moderate oedema were noted
one hour after patch removal. The responses increased in severity and at subsequent observations were identified as well -
defined and moderate to severe oedema, haemorrhage of the dermal capillaries, blanching of the skin, a brown discolouration of theepidermis, scabbing, loss of skin flexibility, a straw-coloured crust (possible hyperkeratinisation), desquamation, thickening of the
skin, reduced re-growth of fur and glossy skin. Scar tissue, indicative of dermal corrosion was noted in five out of six rabbits.

Other effects:

No data.

Any other information on results incl. tables

Summary of dermal irritation (following 4-h application)

Animal no.	Effect	Hour	Days after application							Mean score erythema (24/48/72 h)	Mean score oedema (24/48/72 h)
		1	1	2	3	7	14
25 M	Erythema Oedema	2 2	3 4	2 4	? ?	? ?	? ?			2.5?	4?
28 F	Erythema Oedema	2 2	3 4	3 3	? ?	? ?	0 ?			3?	3.5?
31 M	Erythema Oedema	2 3	3 4	3 4	3 3	? ?	? ?			3	3.67
33 M	Erythema Oedema	2 2	3 4	3 4	3 3	? ?	? ?			3	3.67
73 M	Erythema Oedema	2 2	2 4	2 4	2 3	? ?	? 0			2	3.67
134 F	Erythema Oedema	1 2	2 4	3 3	? ?	? ?	? ?			2.5?	3.5?
Mean all animals										2.67?	3.67?

? Unable to evaluate degree of erythema or oedema due to presence of other adverse dermal reactions

At day 7: scabs, dry straw-coloured crust, sometimes flaking from the skin (possible hyperkeratinisation)

At day 14: desquamation, thickening of the skin, scabs, scar tissue, reduced re-growth of fur, skin glossy in appearance (keratinolysis)

Applicant's summary and conclusion

Interpretation of results:

Category 1C (corrosive) based on GHS criteria

Remarks:

Migrated information

Conclusions:

The test material was considered to be corrosive (Category 1C) to the rabbit skin according to OECD-GHS. This was essentially
based on the formation of scar tissue, indicative of dermal corrosion, in 5 out of 6 rabbits.

Executive summary:

A study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method used followed the recommendations of the OECD Guidelines for Testing of Chemicals No. 404 "Acute Dermal Irritation/Corrosion" and Method B4 of the EC. A single

4 -hour, semi-occluded application of the test material to the intact skin of six rabbits produced severe dermal responses. Scar tissue, indicative of dermal corrosion was noted in 5 out of 6 rabbits 14 days after application. The test material was therefore classified as corrosive (Category 1C) to the rabbit skin, according to OECD/GHS criteria.