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Description of key information

Skin irritation (OECD 404), rabbit: not irritating at a specific concentration of 30% (v/v), irritating at concentrations > 30% (v/v)

Eye irritation (OECD 405), rabbit: irritating at a specific concentration of 30% (v/v), severe eye damage at concentrations > 30% (v/v)

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:
2004-11-09 to 2004-11-30
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
other: SPF albino rabbits of the stock Chbb:HM
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: DIMED Schönwalde GmbH, Schönwalde, Germany; Charles River Deutschland GmbH, Kißegg, Germany
- Age at study initiation: 15-24 months
- Weight at study initiation: 2200-3100 g
- Housing: three female rabbits were caged individually in a polyphenyl (PPE) cage
- Diet: pelleted Altromin 2123, Lage, Lippe, ad libitum
- Water: (tap/filtered) water, ad libitum
- Acclimation period: at least 7 days

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

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Controls:
other: untreated site of the same animal served as control
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
Initial test: 3 min, 1 and 4 h
Confirmatory test: 4 h
Observation period:
14 days
Reading time points: 1, 24, 48, 72 h and 7 and 14 days
Number of animals:
3 females
Details on study design:
TEST SIDE:
- Area of exposure: 6.25 cm² on the left side of the back
- Type of wrap: The treated skin was covered with adhesive Gothaplast tape (2.5 cm)

REMOVAL OF TEST SUBSTANCE:
- Washing: Residual test material was removed with mild soap and lukewarm water.
- Time after start of exposure: 3 min, 1 and 4 h

SCORING SYSTEM:
Draize scoring system
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritant / corrosive response data:
- Animal #1 used in the initial test showed a well-defined erythema on the posterior left test field immediately after the application.
- 1 h after the termination of exposure a well-defined erythema was observed on the posterior left test field of animal #1. Animal #2 showed a well-defined erythema on the anterior left test field, whereas a very slight erythema was observed on the anterior left test field of animal #3.
- 24, 48 and 72 h after the termination of exposure animal #1 showed a very slight erythema on the posterior left test field. A well-defined erythema and a very slight oedema were observed on the anterior left test field of animal #2. Animal #3 showed no skin reactions.
- 7 days after the termination of exposure small, white scales were still observed on approximately 60% of the anterior left test area of animal #2, whereas animal #1 showed no skin reactions anymore.
- 14 days after the termination of exposure animal #2 was free of any signs of skin irritation, too.
- The mean value for erythema and oedema formation calculated from these individual scores was 1.0 and 0.3 respectively.

Table 1: Summary of erythema and edema scores

Observation time

Rabbit No.

1

2

3

Erythema

Edema

Erythema

Edema

Erythema

Edema

1 h

2

0

2

0

1

0

24 h

1

0

2

1

0

0

48 h

1

0

2

1

0

0

72 h

1

0

2

1

0

0

Mean value

24 + 48 + 72 h

1

0

2

1

0

0

Mean value

24 + 48 + 72 h (all animals)

1

0

 
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)

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:
2004-11-29 to 2004-12-28
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
other: SPF albino rabbits of the stock Chbb:HM
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: DIMED Schönwalde GmbH, Schönwalde, Germany
- Age at study initiation: approximately 8 months
- Weight at study initiation: 2100-2200 g
- Housing: three male rabbits were caged individually in a polyphenyl (PPE) cage
- Diet: pelleted Altromin 2123, Lage, Lippe, ad libitum
- Water: (tap/filtered) water, ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±3
- Humidity (%): 55±15
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
water
Controls:
other: the untreated eye served as control
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
24 h
Observation period (in vivo):
21 days
reading time points: 1, 24, 48 and 72 h and 7, 14 and 21 days
Number of animals or in vitro replicates:
3 males
Details on study design:
REMOVAL OF TEST SUBSTANCE:
- Washing: The treated eye was rinsed with 20 mL 0.9% sodium chloride solution
- Time after start of exposure: 24 h
SCORING SYSTEM:
- Draize scoring system
TOOL USED TO ASSESS SCORE:
- fluorescein
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 21 days
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 21 days
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 21 days
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.67
Max. score:
3
Reversibility:
fully reversible within: 21 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.67
Max. score:
3
Reversibility:
fully reversible within: 21 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.67
Max. score:
3
Reversibility:
fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritant / corrosive response data:
- 1 h after the application of the test item the animals showed scattered or diffuse areas of opacity with details of iris clearly visible on more than one quarter of the cornea area, a conjunctiva with diffuse, crimson colour and individual vessels not easily discernible, a swelling above normal and a flow of tears around the whole eye were observed.
- 24 h after the application of the test item the animals showed scattered or diffuse areas of opacity with details of iris clearly visible on more than one half of the cornea area, an iris with markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia and existence of reaction to light, a conjunctiva with diffuse beefy red and an obvious swelling with partial eversion of lids were observed.
- 48 h after the application of the test item the animals showed scattered or diffuse areas of opacity with details of iris clearly visible on more than one half of the cornea area, an iris with markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia and existence of reaction to light, a conjunctiva with diffuse beefy red and an obvious swelling with partial eversion of lids were observed.
- 72 h after the application of the test item the animals showed scattered or diffuse areas of opacity with details of iris clearly visible on more than one half of the cornea area, an iris with markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia and existence of reaction to light, a conjunctiva with diffuse, crimson colour and individual vessels not easily discernible as well as an obvious swelling with partial eversion of lids were observed.
- 7 days after the application of the test item the animals showed scattered or diffuse areas of opacity with details of iris clearly visible on more than half of the cornea area, some hyperaemic, conjunctival blood vessels and a swelling above normal were observed.
- 14 days after the application of the test item all animals showed scattered or diffuse areas of opacity with details of iris clearly visible on about one quarter of the cornea area.
- the eye irritating effects were fully reversible within 21 days.

Table 1: Summary of eye irritation study

Rabbit #

 

Time [h]

 

conjunctivae

 

iris

 

cornea

 

 

conjunctivae

 

iris

 

cornea

 

redness

swelling

redness

swelling

1

 

 

 

 

1

2

1

0

1

 

24

3

2

1

1

48

3

2

1

1

72

2

2

1

1

average

2,67

2

1

1

Time to reversion

14 days

14 days

7 days

14 days

2

 

 

 

 

1

2

1

1

1

 

 

24

3

1

1

1

48

3

1

1

1

72

2

1

1

1

average

2.67

1.0

1.0

1.0

Time to reversion

7 days

7 days

7 days

21 days

3

 

 

 

 

1

2

1

1

1

 

 

24

2

1

1

2

48

2

1

1

1

72

1

1

1

1

average

1.67

1.0

1.0

1.33

Time to reversion

14 days

14 days

14 days

14 days
Interpretation of results:
other: Eye irrit. 2, H319. Classification according to Regulation (EC) No. 1272/2008 (CLP/EU GHS).
Conclusions:
SCL:
> 30%: Eye dam. Category 1 (H318)
≤ 30% and > 1%: Eye irrit. Category 2 (H319)
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

The skin irritation properties of Glycine, N-methyl-, N-coco acyl derivatives, sodium salts (CAS 61791-59-1) have been investigated in accordance with OECD TG 404 under GLP conditions (Frey-Tox, 2004a). In the study a 30% aqueous solution (highest achievable concentration) of the test substance was applied to the clipped skin of three female SPF Albino rabbits for 3 min, 1 and 4 h in an initial test and for 4 h in a confirmatory test using semi-occlusive coverage. The treated skin was observed and evaluated at 1, 24, 46 and 72 h as well as on day 7 post-application. One hour post application two animals showed well-defined erythema (grade 2) and one animal showed slight erythema (grade 1) and no edema were observed. 24 to 72 hours post application slight to well-defined erythema were observed in these animals. One animal also developed slight edema (grade 1). The effects were fully reversible within 7 to 14 days. The remaining animal showed slight erythema (grade 1) one hour post-application which was fully reversible within 24 h. No edema was observed in this animal. Hence, under the applied experimental conditions the mean score for erythema and for edema was calculated to be 1.0 and 0.3, respectively. Based on the results of the study the test substance shall not be classified as skin irritating.

 

Eye irritation

The eye irritation properties of Glycine, N-methyl-, N-coco acyl derivatives, sodium salts (CAS 61791-59-1) have been investigated in accordance with OECD TG 405 under GLP conditions (Frey-Tox, 2004b). For the assessment of the eye irritation properties 0.1 mL of a 30% aqueous solution (highest achievable concentration) of the test substance was instilled in the eye of three male Albino rabbits. The eyes were examined and the changes were graded according to the Draize scoring system 1, 24, 48 and 72 hours and 7, 14 and up to 21 days post application. One hour post-application all animals showed cornea opacity (grade 1) and redness (grade 1 or 2) as well as chemosis (grade 1) regarding the conjunctiva. Furthermore, two animals showed an effect on light sensitivity of the iris (grade 1). 24 to 72 hours post-application, mean values of cornea opacity (grade 1), effects on the iris (grade 1) and redness (grade 2.67) and chemosis (grade 2) were observed at two animals. All effects were fully reversible within 14 to 21 days, respectively. Corneal opacity (grade 1.33), iris effects (grade1) and redness/chemosis (grade 1.67/1) of the conjunctiva were observed at the remaining animal 24 to 72 h post-application and were fully reversible within 14 days. In summary, the substance is considered to be irritating to the eyes in the concentration of 30% (v/v). However, since no data for the neat substance or solutions > 30% (v/v) are available, the neat substance is assumed to cause severe damage to eyes in a worst case assumption.

Justification for classification or non-classification

The available data on skin irritation/corrosion of Glycine, N-methyl-, N-coco acyl derivatives, sodium salts (CAS 61791-59-1) which was derived with a 30% (v/v) aqueous solution do not meet the criteria for classification according to Regulation (EC) No. 1272/2008 (CLP). However, as no experimental data are available for higher concentrations, the neat substance is considered to be irritating to the skin (Skin Irrit. 2, H315) in a worst case assumption.

The available data on eye irritation of Glycine, N-methyl-, N-coco acyl derivatives, sodium salts (CAS 61791-59-1) meet that the criteria for classification as Eye Irrit. 2 (H319) at the tested concentration of 30%. However, since no data for the neat substance are available as the tested solution containing 30% Glycine, N-methyl-, N-coco acyl derivatives, sodium salts (CAS 61791-59-1) is the highest achievable concentration, the substance is considered to meet the classification criteria for Eye Damage 1 (H318) at concentrations > 30%. Therefore, the following specific concentration limits with respect to eye irritation / eye damage are established.

SCLs for eye irritation / severe eye damage:

> 30%: Eye Damage 1 (H318)

≤ 30% and ≥ 1%: Eye Irrit. 2 (H319)

< 1%: no classification warranted.