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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

Category classification: 
Skin irritation (OECD 404):
DSD C, R34; CLP Skin Corr. 1B (>30%) 
DSD Xi, R38; CLP Skin Irrit. 2 (EC 931-700-2, 30% a. i.) 
Not classified for skin irritation (CAS 68424-94-2, 16% a.i.; CAS 683-10-3, 10% a.i.)
Eye irritation (OECD 405):
Implicit in classification as corrosive (>30%) 
DSD Xi, R41; CLP Eye Dam. 1 (CAS 68424-94-2, 30% a. i.) 
DSD Xi, R36; CLP Eye Irrit. 2 (CAS 683-10-3, 10%) 
CLP Eye Irrit. 2 (CAS 68424-94-2, 16%)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin 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:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Chemisch pharmazeutische Fabrik Dr. Karl Thomae GmbH, 88400 Biberach; SPF-breeding
- Age at study initiation: 3-5months
- Weight at study initiation: 2.0 - 2.2 kg
- Housing:individually
- Diet (e.g. ad libitum): Altromin 2123 maintenance diet for rabbits, Altromin GmbH, Lage/LIppe, ad libitum; additionally 15 g hay/day
- Water (e.g. ad libitum): tap water from automatic devices, ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 50 ± 20
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Concentration (if solution): 30 % active
Duration of treatment / exposure:
4 hours
Observation period:
14 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: dorsal area of the body
- Type of wrap if used: adhesive patch with 2.5 x 2.5 cm cellulose padding (custom-made by Fa. Beiersdorf AG, Hamburg)


REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with lukewarm tap water
- Time after start of exposure: 4 hours


SCORING SYSTEM: Draize scoring
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Dry, rough skin surface after 72 hours, coarse scales after 72 hours and 7 days, desquamation after 7 days, reversible by day 14
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Dry, rough skin surface after 72 hours, fine scales and desquamation after 7 days, reversible by day 14
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Dry, rough skin surface after 72 hours, fine scales and desquamation after 7 and 14 days
Irritant / corrosive response data:
After removal of the dressing the animals showed very slight to slight edema between 30 minutes and 72 hours, and very slight to moderate erythema up to day 7. The skin surface was dry, rough and showed fine to coarse scales, with desquamation. The irritation effects were fully reversible within 14 days.

According to the criteria of Directive 67/548/EEC and the criteria of Regulation (EC) No 1272/2008 the test substance at a concentration of 30% active has to be classified as irritating to the skin (R38, CLP Skin Irrit. 2).

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
CLP: Skin irrit. 2, H315
DSD: Xi, R38
Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of 3 animals
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
fully reversible within: 14 d
Remarks on result:
other: EC 931-700-2 (30%)
Irritation parameter:
edema score
Basis:
mean
Remarks:
of 3 animals
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 d
Remarks on result:
other: EC 931-700-2 (30%)
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: average of 24 and 72 h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: no individual scores reported. CAS 68424-94-2 (16%)
Irritation parameter:
edema score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: average of 24 and 72 h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: no individual scores reported. CAS 68424-94-2 (16%)
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Remarks on result:
other: CAS 683-10-3 (10%)
Irritation parameter:
edema score
Basis:
mean
Remarks:
of 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Remarks on result:
other: CAS 683-10-3 (10%)
Irritant / corrosive response data:
Information given in the result table correspond to the sources of the key studies. Three further supporting studies are available with EC 931-700-2. None of these studies lead to a classification as a skin irritant but it has to be stated that for these studies no purities on the test substances were given.
Other effects:
EC 931-700-2 (30%): The skin surface was dry, rough and showed fine to coarse scales, with desquamation. The irritation effects were fully reversible within 14 days.
Interpretation of results:
Category 1B (corrosive) based on GHS criteria
Conclusions:
As result of all data given the following conclusion can be made:
Skin irritation (OECD 404):
Skin Corr. 1B (>30%)
Skin Irrit. 2 (16 - 30%)
Executive summary:

Several studies are available from structural analogues CAS 68424 -94 -2, EC 931 -700 -2 and 683 -10 -3. It is concluded that Betaines, C12-14 (even numbered)-alkyldimethyl, potassium salt; aqueous commercial product(s) is corrosive to skin (Cat. 1B) at concentration above 30%. At concentrations between 16% and 30% it has to be classified as skin irritant (Cat. 2) as found from studies with structural analogues at different concentrations. As explained in the justification for type of information, the differences in molecular structure between the target and the source are unlikely to lead to differences in the skin irritation potential that are higher than the typical experimental error of the test method.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Comparable to guideline study with acceptable restrictions (readings at 24 and 72 hours only, test terminated after 72 h, no information regarding reversibility, purity of test substance not reported, 24h occlusive dressing according to former guideline)
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
readings at 24 and 72 hours only, test terminated after 72 h, no information regarding reversibility, purity of test substance not reported, 24h occlusive dressing according to former guideline
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 1.92-2.36kg
- Housing: anodised aluminium cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21±2
- Humidity (%): 60±10
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5mL
- Concentration (if solution): as supplied


Duration of treatment / exposure:
24h
Observation period:
24 and 72h
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: 2.5cm²
- % coverage: 10%
- Type of wrap if used: Lint squares were placed in contact with the animal's skin and secured in position by the attached 'Sleek' adhesive tape. The entire trunk of the animal was then encircled with a length of elastic adhesive bandage 7.5cm wide.

SCORING SYSTEM: Draize
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: average 24 and 72h
Score:
1.83
Max. score:
4
Reversibility:
not fully reversible within: 72h (end of observation time)
Irritation parameter:
edema score
Basis:
mean
Time point:
other: average 24 and 72h
Score:
0.83
Max. score:
4
Reversibility:
not fully reversible within: 72h (end of observation time)
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: average 24 and 72h
Score:
1.5
Max. score:
4
Reversibility:
not fully reversible within: 72h (end of observation time)
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: average 24 and 72h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 72h (end of observation time)
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: average 24 and 72h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 72h (end of observation time)
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
other: average 24 and 72h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 72h (end of observation time)
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
other: average 24 and 72h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 72h (end of observation time)
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
other: average 24 and 72h
Score:
1.5
Max. score:
4
Reversibility:
not fully reversible within: 72h (end of observation time)
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: average 24 and 72h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 72h (end of observation time)
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: average 24 and 72h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 72h (end of observation time)
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: average 24 and 72h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 72h (end of observation time)
Irritation parameter:
edema score
Basis:
animal #4
Time point:
other: average 24 and 72h
Score:
1.5
Max. score:
4
Reversibility:
not fully reversible within: 72h (end of observation time)
Irritation parameter:
edema score
Basis:
animal #5
Time point:
other: average 24 and 72h
Score:
1.5
Max. score:
4
Reversibility:
not fully reversible within: 72h (end of observation time)
Irritation parameter:
edema score
Basis:
animal #6
Time point:
other: average 24 and 72h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 72h (end of observation time)
Irritant / corrosive response data:
Sample C/3169, Empigen BB has well-defined irritating effects to rabbit skin. No corrosive effects were observed.

Table 1: Individual irritation scores:

Skin effect

Erythema

Edema

Scoring

Readings at

Mean

 

Readings at

Mean

 

24h

72h

24h

72h

Animal No. /sex

#1

 

2

 

1

 

1.5

 

1

 

0

 

0.5

#2

2

2

2.0

1

0

0.5

#3

2

2

2.0

1

0

0.5

#4

2

2

2.0

2

1

1.5

#5

2

2

2.0

2

1

1.5

#6

1

2

1.5

1

0

0.5

Although there were no data on reversibility, the decrease of the edema scores from 24 to 72h and the mean scores that were under the guideline values led to no classification according to EU Directive 67/548/EEC and Regulation (EC) No 1272/2008. However the consisting well-defined irritation after 72h and missing data on reversibility makes classification not indisputable.

Interpretation of results:
GHS criteria not met
Conclusions:
CLP: not classified
DSD: not classified
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Comparable to guideline studies with acceptable restrictions (readings at 24 and 72 hours only, test terminated after 72 h, no information regarding reversibility, purity of test substance not reported, 24h occlusive dressing according to former guideline)
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
readings at 24 and 72 hours only, test terminated after 72 h, no information regarding reversibility, purity of test substance not reported, 24h occlusive dressing according to former guideline
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 1.46-2.20kg
- Housing: anodised aluminium cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21±2
- Humidity (%): 60±10
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5mL
- Concentration (if solution): as supplied


Duration of treatment / exposure:
24h
Observation period:
24 and 72h
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: 2.5cm²
- % coverage: 10%
- Type of wrap if used: Lint squares were placed in contact with the animal's skin and secured in position by the attached 'Sleek' adhesive tape. The entire trunk of the animal was then encircled with a
length of elastic adhesive bandage 7.5cm wide.

SCORING SYSTEM: Draize
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: average 24 and 72h
Score:
1.83
Max. score:
4
Reversibility:
not fully reversible within: 72h (end of observation time)
Irritation parameter:
edema score
Basis:
mean
Time point:
other: average 24-72h
Score:
1.08
Max. score:
4
Reversibility:
not fully reversible within: 72h (end of observation time)
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: average 24 and 72h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 72h (end of observation time)
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: average 24 and 72h
Score:
2.5
Max. score:
4
Reversibility:
not fully reversible within: 72h (end of observation time)
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: average 24 and 72h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 72h (end of observation time)
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
other: average 24 and 72h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 72h (end of observation time)
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
other: average 24 and 72h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 72h (end of observation time)
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
other: average 24 and 72h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 72h (end of observation time)
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: average 24 and 72h
Score:
1.5
Max. score:
4
Reversibility:
not fully reversible within: 72h (end of observation time)
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: average 24 and 72h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72h (end of observation time)
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: average 24 and 72h
Score:
1.5
Max. score:
4
Reversibility:
not fully reversible within: 72h (end of observation time)
Irritation parameter:
edema score
Basis:
animal #4
Time point:
other: average 24 and 72h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritation parameter:
edema score
Basis:
animal #5
Time point:
other: average 24 and 72h
Score:
1.5
Max. score:
4
Reversibility:
not fully reversible within: 72h (end of observation time)
Irritation parameter:
edema score
Basis:
animal #6
Time point:
other: average 24 and 72h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72h (end of observation time)
Irritant / corrosive response data:
Sample C/3170, Empigen BB has well-defined to moderate irritating effects to rabbit skin. No corrosive effects were observed.

Tabelle 1: Individual irritation scores:

Skin effect

Erythema

Edema

Scoring

Readings at

Mean

 

Readings at

Mean

 

24h

72h

24h

72h

Animal No. /sex

#1

 

2

 

2

 

2.0

 

2

 

1

 

1.5

#2

3

2

2.5

2

0

1.0

#3

2

2

2.0

2

1

1.5

#4

1

0

0.5

0

0

0.0

#5

2

2

2.0

2

1

1.5

#6

2

2

2.0

2

0

1.0

Although there were no data on reversibility, the decrease of the edema scores from 24 to 72h and the mean scores that were under the guideline values lead to no classification according to EU Directive 67/548/EEC and Regulation (EC) No 1272/2008. However the well-defined irritation that was left after 72h and the missing data on reversibility makes classification not indisputable.

Interpretation of results:
GHS criteria not met
Conclusions:
CLP: not classified
DSD: not classified
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions (purity of test substance not reported, occlusive dressing according to former guideline)
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
purity of test substance not reported, occlusive dressing according to former guideline
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: A. Smith, 7 Kydcomb Road, Warlingham, Surrey
- Weight at study initiation: 2.3-3.0kg
- Housing: individually in grid bottomed metal cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22
- Humidity (%): 53-65
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5mL
- Concentration (if solution): undiluted

Duration of treatment / exposure:
4h
Observation period:
1, 24, 48, 72 and 168h
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: 2.5cmx2.5cm
- Type of wrap if used: A lint pad was placed onto the selected area of skin of an animal and held in position by a strip of 5cm wide 'Sleek' plastic adhesive strapping, this also acting as an occlusive barrier. The trunk of the animal was then encircled with a length of 'Elastoplast' elastic adhesive bandage 7.5cm wide to keep the dosed material in contact with the skin.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, cotton wool soaked in water at 37°C
- Time after start of exposure: 4h


SCORING SYSTEM: Draize
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: average 24, 48 and 72h
Score:
1.17
Max. score:
4
Reversibility:
not fully reversible within: 7 days (end of observation time)
Irritation parameter:
edema score
Basis:
mean
Time point:
other: average 24, 48 and 72h
Score:
0.72
Max. score:
4
Reversibility:
not fully reversible within: 7 days (end of observation time)
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: average 24, 48 and 72h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days (end of observation time)
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: average 24, 48 and 72h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: average 24, 48 and 72h
Score:
0.33
Max. score:
4
Reversibility:
not fully reversible within: 7 days (end of observation time)
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
other: average 24, 48 and 72h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days (end of observation time)
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
other: average 24, 48 and 72h
Score:
1.66
Max. score:
4
Reversibility:
fully reversible within: 7 days (end of observation time)
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
other: average 24, 48 and 72h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 7 days (end of observation time)
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: average 24, 48 and 72h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: desquamation from skin surface at 72h reading
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: average 24,48 and 72h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: average 24, 48 and 72h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritation parameter:
edema score
Basis:
animal #4
Time point:
other: average 24, 48 and 72h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 7 days (end of observation time)
Remarks on result:
other: slight desquamarion from skin surface from 72h to 7 day reading
Irritation parameter:
edema score
Basis:
animal #5
Time point:
other: average 24, 48 and 72h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days (end of observation time)
Irritation parameter:
edema score
Basis:
animal #6
Time point:
other: average 24, 48 and 72h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48h
Remarks on result:
other: slight desquamation from skin surface
Irritant / corrosive response data:
Empigen BB has slightly irritating effects on rabbit skin. No corrosive action was observed during the study.

Table 1: Individual irritation scores:

Skin effect

Erythema

Edema

Scoring

Readings at

Mean 24-72h

Readings at

Mean

24-72h

24h

48h

72h

168h

24h

48h

72h

168h

Animal No. /sex

#1

 

2

 

2

 

2

 

2

 

2.0

 

2

 

2

 

2

 

1

 

2.0

#2

0

0

0

0

0.0

0

0

0

0

0.0

#3

0

0

1

1

0.3

0

0

0

0

0.0

#4

2

2

2

1

2.0

1

1

1

1

1.0

#5

2

2

1

0

1.7

2

1

0

0

1.0

#6

1

1

1

1

1.0

1

0

0

0

0.3

Although there was slight erythema and edema left at the end of the observation period of 7 days, the decrease of the effects by time makes reversibility assumable. Therefore Empigen BB has not to be classified according to DSD and CLP regulation. However missing data on reversibility makes classification not indisputable.

Interpretation of results:
GHS criteria not met
Conclusions:
CLP: not classified
DSD: not classified
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions Occlusive dressing, 48h reading is missing, only 72h observation time, no individual scores reported.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
occlusive dressing, 48h reading is missing, only 72h observation time
GLP compliance:
not specified
Species:
rabbit
Strain:
other: albino, not further specified
Type of coverage:
occlusive
Preparation of test site:
other: shaved and abraded, respectivley
Vehicle:
not specified
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5mL
- Concentration (if solution): 16%


Duration of treatment / exposure:
24h
Observation period:
24 and 72h
Number of animals:
3, non-abraded and additionally abraded on the posterior of the clipped area
Details on study design:
TEST SITE
- Area of exposure: 2x2, unit not specified
- % coverage: 10%
- Type of wrap if used: Webril patches and the entire experimental area sealed with Blenderm Surgical Tape

SCORING SYSTEM: Draize
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: average 24 and 72h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 72h
Remarks on result:
other: no individual scores reported
Irritation parameter:
edema score
Basis:
mean
Time point:
other: average 24 and 72h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 72h
Remarks on result:
other: no individual scores reported
Irritant / corrosive response data:
The scores of the abraded skin areas were the same than for the non-abraded sites.

Coco alkyldimethyl betaines when applied as 16% solids solution to rabbit skin for 24h show only slight irritating potential after 24h that was fully reversible within 72h and has therefore not to be classified according to the criteria of EU Directive 67/548/EEC and the criteria of Regulation (EC) No 1272/2008.

Interpretation of results:
GHS criteria not met
Conclusions:
CLP: not classified
DSD: not classified
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions. Only 10% (v/v) tested.
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
only 10% (v/v) tested
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, Sandbach, Cheshire, U.K., and Nottingham University, School of Agriculture, Sutton Bonington, Leicestershire, U.K.
- Age at study initiation: 12-16 weeks
- Weight at study initiation: 2.44 - 2.61 kg
- Housing: individually housed in suspended metal cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-21°C
- Humidity (%): 65
- Air changes (per hr): 15/h
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5mL
- Concentration (if solution): 10%


Duration of treatment / exposure:
4h
Observation period:
1, 24, 48 and 72h
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2.5cmx2.5cm
- Type of wrap if used: A gauze patch was secured in position with a strip of surgical adhesive tape (BLENDERM: approximate size 25 mm x 40 mm). To prevent the animals from interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset (TUBIGRIP).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, gentle swabbing with cotton wool soaked in distilled water
- Time after start of exposure: 4h

SCORING SYSTEM: Draize
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritant / corrosive response data:
No corrosive effects were noted. Very slight erythema was noted at all treated skin sites one hour after removal of the patches. Very slight edema was also noted at one treated skin site at this time. All treated skin sites appeared normal at subsequent 24, 48 and 72-hour observations.

The test material (10% v/v aqueous solution), was found to be non-irritant to rabbit skin and has therefore not to be classified according to DSD and CLP regulation.

Interpretation of results:
GHS criteria not met
Conclusions:
CLP: not classified
DSD: not classified
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions. Only 72h observation time, purity of test substance not specified.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
only 72h observation time, purity of test substance not specified
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Gorseside Rabbits, Northchurch, Berkhamsted, Hertfordshire
- Housing: individually in grid bottomed metal cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15-20
- Humidity (%): 30-77
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1mL
- Concentration (if solution): as supplied


Duration of treatment / exposure:
single instillation without washout
Observation period (in vivo):
24, 48 and 72h after treatment
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: standard light source
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: average 24, 48 and 72h
Score:
0.22
Max. score:
4
Reversibility:
fully reversible within: 72h
Irritation parameter:
iris score
Basis:
mean
Time point:
other: average 24, 48 and 72h
Score:
0.55
Max. score:
2
Reversibility:
not fully reversible within: 72h (end of observation time)
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: average 24, 48 and 72h
Score:
1.33
Max. score:
3
Reversibility:
not fully reversible within: 72h (end of observation time)
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: average 24, 48 and 72h
Score:
0.83
Max. score:
4
Reversibility:
not fully reversible within: 72h (end of observation time)
Irritant / corrosive response data:
ST0056 shows irritating effects to rabbit eyes. Slight irritation was left in 4 out of 6 animals after 72h observation period. No corrosive effects were observed.

Table 1: Individual eye irritation scores

Rabbit No.

Scoring [h]

Cornea

Iris

Conjunctiva

Redness

Chemosis

748

24

1

1

2

2

 

48

0

0

1

0

 

72

0

0

0

0

 

Mean

0.3

0.3

1.0

0.7

749

24

1

1

1

1

 

48

1

1

1

1

 

72

0

1

0

0

 

Mean

0.7

1.0

0.7

0.7

750

24

0

1

2

1

 

48

0

0

1

0

 

72

0

1

1

1

 

Mean

0.0

0.7

1.3

0.7

752

24

0

0

1

1

 

48

0

0

1

0

 

72

0

0

0

0

 

Mean

0.0

0.0

0.7

0.3

753

24

1

1

2

4

 

48

0

1

2

1

 

72

0

1

1

0

 

Mean

0.3

1.0

1.7

1.7

423

24

0

1

2

2

 

48

0

0

1

1

 

72

0

0

1

0

 

Mean

0.0

0.3

1.3

1.0

Because the effects were decreasing during the observation time (which makes reversibility assumable) and the guideline values were not reached, ST0056 does not have to be classified according to EU Directive 67/548/EEC and Regulation (EC) No 1272/2008.

Interpretation of results:
GHS criteria not met
Conclusions:
CLP: not classified
DSD: not classified
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions. Only 72h observation time, purity of test substance not specified.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
only 72h observation time, purity of test substance not specified
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Gorseside Rabbits, Northchurch, Berkhamsted, Hertfordshire
- Housing: individually in grid bottomed metal cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15-20
- Humidity (%): 30-77
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1mL
- Concentration (if solution): as supplied


Duration of treatment / exposure:
single instillation without washout
Observation period (in vivo):
24, 48 and 72h after treatment
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: standard light source
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: average 24, 48 and 72h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritation parameter:
iris score
Basis:
mean
Time point:
other: average 24, 48 and 72h
Score:
0.28
Max. score:
2
Reversibility:
fully reversible within: 72h
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: average 24, 48 and 72h
Score:
1.05
Max. score:
3
Reversibility:
not fully reversible within: 72h (end of observation time)
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: average 24, 48 and 72h
Score:
0.72
Max. score:
4
Reversibility:
fully reversible within: 72h
Irritant / corrosive response data:
ST0055 shows slight irritating effects to rabbit eyes. No corrosive effects were observed.

Table 1: Individual eye irritation scores

Rabbit No.

Scoring [h]

Cornea

Iris

Conjunctiva

Redness

Chemosis

743

24

0

1

2

0

 

48

0

0

1

0

 

72

0

0

0

0

 

Mean

0.0

0.3

1.0

0.0

744

24

0

1

2

2

 

48

0

0

2

0

 

72

0

0

0

0

 

Mean

0.0

0.3

1.3

0.7

745

24

0

1

1

2

 

48

0

1

1

0

 

72

0

0

0

0

 

Mean

0.0

0.7

0.7

0.7

746

24

0

1

2

4

 

48

0

0

2

1

 

72

0

0

0

0

 

Mean

0.0

0.3

1.3

1.7

747

24

0

0

1

1

 

48

0

0

0

0

 

72

0

0

0

0

 

Mean

0.0

0.0

0.3

0.3

396

24

0

0

2

2

 

48

0

0

2

1

 

72

0

0

1

0

 

Mean

0.0

0.0

1.7

1.0

Although the effects were not reversible in one animal within the observation time of 72h the decrease of the scores and the slight effect that was left do not justify a classification of ST0055 according to EU Directive 67/548/EEC and Regulation (EC) No 1272/2008.

Interpretation of results:
GHS criteria not met
Conclusions:
CLP: not classified
DSD: not classified
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions. No washing, only 7 days observation period
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
No washing, only 7 days observation period
Qualifier:
according to guideline
Guideline:
other: Leberco internal assay number 99763 (Draize method)
GLP compliance:
no
Species:
rabbit
Strain:
other: albino, not further specified
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated left eyes served as controls
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
not washed out
Observation period (in vivo):
7 days (examination every 24 hours for four days and then again on day 7)
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no


SCORING SYSTEM: Draize
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.66
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.66
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not reversible
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not reversible
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not reversible
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 7 days (end of observation period)
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not reversible
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 7 days (end of observation period)
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.66
Max. score:
4
Reversibility:
not fully reversible within: 7 days (end of observation period)
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days (end of observation period)
Irritant / corrosive response data:
The test material caused corneal involvement and iris involvement and conjunctival irritation not clearing on the seventh day of observation.

According to the criteria of the EU Directive 67/548/EEC and the criteria of Regulation (EC) No 1272/2008 the test substance causes serious eye damage (R41 and CLP Eye Dam. 1, respectively).

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
CLP: Eye dam. 1, H318
DSD: Xi, R41
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions. Only 7 days observation period
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
only 7 days observation period
GLP compliance:
no
Species:
rabbit
Strain:
other: albino, not further specified
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated left eyes served as controls
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
not washed out
Observation period (in vivo):
7 days (examination every 24 hours for four days and then again on day 7)
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no


SCORING SYSTEM: Draize
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 7 days (end of observation period)
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: no effects
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: average 24, 48, 72 hours
Score:
0
Max. score:
2
Reversibility:
other: no effects
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: no effects
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.33
Max. score:
3
Reversibility:
not fully reversible within: 7 days (end of observation period)
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.33
Max. score:
3
Reversibility:
not fully reversible within: 7 days (end of observation period)
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48h
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.66
Max. score:
4
Reversibility:
fully reversible within: 48h
Irritant / corrosive response data:
The test material caused corneal involvement and conjunctival irritation not clearing on the seventh day of observation. The test substance induces irritation to rabbit eyes that was remaining after 7 days as slight redness in two animals and slight corneal opacity in one animal.

Table 1: Individual eye irritation scores

Rabbit No. / sex

Scoring

Cornea

Iris

Conjunctiva

Redness

Chemosis

1

24h

1

0

1

1

 

48h

1

0

1

1

 

72h

1

0

1

1

 

4 days

1

0

1

0

 

7 days

0

0

0

0

2

24h

1

0

1

0

 

48h

1

0

1

0

 

72h

1

0

1

0

 

4 days

1

0

1

0

 

7 days

0

0

1

0

3

24h

1

0

2

1

 

48h

1

0

1

1

 

72h

1

0

1

1

 

4 days

1

0

1

1

 

7 days

1

0

1

0

Conclusion: Because of the decrease of the effects over the time a reversibility after 14 or 21 days can be assumed. According to the criteria of EU Directive 67/548/EEC the test substance has not to be classified. According to the criteria of Regulation (EC) No 1272/2008 the test substance is classified as Eye Irrit. 2; H319: Causes serious eye irritation.

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
CLP: Eye irrit. 2, H319
DSD: not classified
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions. Purity of test material not specified, only 72h observation time.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
purity of test material not specified, only 72h observation time
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: A. Smith, Warlingham, Surrey
- Weight at study initiation: 2.2-2.5kg
- Housing: in grid bottomed metal cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 25-71
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated left eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1mL
- Concentration (if solution): as supplied


Duration of treatment / exposure:
the eyes of 3 out of 9 animals were washed 5 seconds after instillation, the other 6 rabbits eyes remained unwashed
Observation period (in vivo):
24, 48 and 72h after instillation
Number of animals or in vitro replicates:
9
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): The eyes of six animals were not washed after dosing with the test material. The treated eyes of the second group of three rabbits were washed five seconds after dosing using 20mL of sterile distilled water warmed to approximately 37°C.
- Time after start of exposure: 5 sec

SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: standard light source
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: average 24, 48 and 72h
Score:
0.06
Max. score:
4
Reversibility:
fully reversible within: 48h
Irritation parameter:
iris score
Basis:
mean
Time point:
other: average 24, 48 and 72h
Score:
0.16
Max. score:
2
Reversibility:
fully reversible within: 48h
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: average 24, 48 and 72h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72h
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: average 24, 48 and 72h
Score:
0.22
Max. score:
4
Reversibility:
fully reversible within: 72h
Irritant / corrosive response data:
ST0045 has irritating effects on rabbit eyes that were fully reversible within the 72h observation time. Iris inflammation and severe conjunctival irritation were observed in the treated eye of one animal of the rinsed group twenty four hours after dosing, one other animal of the group exhibiting slight conjunctival redness. Well defined conjunctival irritation remained in one animal at the forty eight hour examination. Seventy two hours after dosing slight conjunctival irritation remained in this animal.

Table 1: Individual irritation scores of the animals with unrinsed eyes

 

Average irritation score of 24, 48 and 72h

Animal number

Cornea

Iris

Conjunctiva

Chemosis

563

0

0

0.3

0

564

0

0.3

0.6

0

567

0

0.3

0.6

0.33

568

0.33

0

0.6

0

570

0

0

0.6

0.33

571

0

0.33

1.33

0.66

Mean

0.06

0.16

0.67

0.22

According to EU Directive 67/548/EEC and Regulation (EC) No 1272/2008 ST0045 does not have to be classified. However the concentration of the test substance was not determined. The effects remaining in the rinsed eyes group were not considered for classification as these effects were stronger than those observed under more disadvantageous conditions.

Interpretation of results:
GHS criteria not met
Conclusions:
CLP: not classified
DSD: not classified
Endpoint:
eye irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of 3 animals
Time point:
24/48/72 h
Score:
1.44
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: CAS 68424-94-2 (30%)
Irritation parameter:
iris score
Basis:
mean
Remarks:
of 3 animals
Time point:
24/48/72 h
Score:
1.67
Max. score:
2
Reversibility:
not reversible
Remarks on result:
other: CAS 68424-94-2 (30%)
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
of 3 animals
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 7 days (end of observation period)
Remarks on result:
other: CAS 68424-94-2 (30%)
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of 2 animals
Time point:
24/48/72 h
Score:
1.83
Max. score:
4
Reversibility:
not fully reversible within: 7 days (end of observation period)
Remarks on result:
other: CAS 68424-94-2 (30%)
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24, 48, 72 hours
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: CAS 68424-94-2 (30%)
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of 3 animals
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 7 days (end of observation period) for two animals. One animal was fully reversible within 7 days.
Remarks on result:
other: CAS 68424-94-2 (16%)
Irritation parameter:
iris score
Basis:
mean
Remarks:
of 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Remarks on result:
other: CAS 67424-94-2 (16%)
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
of 3 animals
Time point:
24/48/72 h
Score:
1.22
Max. score:
3
Reversibility:
not fully reversible within: 7 days (end of observation period) except one animal which was fully reversible within 7 days
Remarks on result:
other: CAS 67424-94-2 (16%)
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of 3 animals
Time point:
24/48/72 h
Score:
0.66
Max. score:
4
Reversibility:
fully reversible within: 48 h or 7 days
Remarks on result:
other: CAS 67424-94-2 (16%)
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of 3 animals
Time point:
24/48/72 h
Score:
1.11
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: CAS 683-10-3 (10%)
Irritation parameter:
iris score
Basis:
mean
Remarks:
of 3 animals
Time point:
24/48/72 h
Score:
0.78
Max. score:
2
Reversibility:
fully reversible within: 48 h or 7 days
Remarks on result:
other: CAS 683-10-3 (10%)
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
2.22
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
1.78
Max. score:
4
Reversibility:
fully reversible within: 72 h or 7 days
Remarks on result:
other: CAS 683-10-3 (10%)
Irritant / corrosive response data:
Information given in the result table correspond to the sources of the key studies. Eight further supporting studies are available with EC 931-700-2 and CAS 2601-33-4 and CAS 683-10-3. None of these studies lead to a classification as a eye irritant but it has to be stated that for these studies no purities on the test substances were given.
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
As result of all data given the following conclusion can be made:
Eye irritation (OECD 405):
Eye Damage 1 (>16%)
Eye Irrit. 2 (1-16%)
Executive summary:

Several studies are available from structural analogues CAS 68424 -94 -2, CAS 683 -10 -3, EC 931 -700 -2, and CAS 2601-33-4. It is concluded that Betaines, C12-14 (even numbered)-alkyldimethyl, potassium salt; aqueous commercial product(s) is damaging to eyes (Cat. 1) at concentration above 16%. At concentrations between 1% and 16% it has to be classified as eye irritant (Cat. 2) as found from studies with structural analogues at different concentrations. As explained in the justification for type of information, the differences in molecular structure between the target and the source are unlikely to lead to differences in the eye irritation potential that are higher than the typical experimental error of the test method.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

There is no data available on the skin and eye irritating properties of N,N-dimethyl-alkyl-1-amines, reaction products with alkali hydroxide and chloroacetic acid. However, there is reliable data for the structural related substances CAS 68424-94-2, CAS 683-10-3, CAS 2601-33-4 and EC 931-700-2. The target substance and the source substances show pronounced structural and physico-chemical similarities. Therefore, read-across was performed based on an analogue approach. For a detailed justification of the analogue approach, please refer to section 13 of the technical dossier.

The most sensitive study addressing skin irritation was conducted with 30% aqueous solution of EC 931-700-2 for 4 hours under semiocclusive conditions (Kreiling, 1994). This study demonstrated irritating properties that cause a classification as R38 according to the criteria of EU Directive 67/548/EEC (DSD) and Skin Irrit. 2 according to the criteria of Regulation (EC) No 1272/2008 (CLP). Other studies performed with EC 931-700-2 as supplied (not further specified) for 24 hours under occlusive conditions did only indicate slight irritant properties, but not sufficient for a classification (Haynes, 1985; Haynes, 1978a, Haynes, 1978b). For CAS 68424-94-2 two studies were performed with exposure for 24 hours under occlusive conditions, one with a test material containing 16% solids (Levenstein, 1979b), the other one with an unspecified test material (Levenstein, 1979); therefore the latter was not considered any further. Both studies indicated only mild irritating potential. Although not providing individual animal data, the low mean scores for the 3 tested animals for 24 and 72 hours and the complete reversibility within the observation period of 72 hours allow considering the study by Levenstein (1979b) as appropriate for assessment. It demonstrates that there is no skin irritating effect at substance concentrations up to 16%, therefore this study was chosen as additional key study due to its importance for the determination of specific concentration limits. There is only one reliable data source available for CAS 683-10-3 (Jones and Guest, 1987). The test was performed for 4 hours under semiocclusive conditions with 10% test material concentration. This test failed to demonstrate irritating effects on the skin, either.

In addition to the information from animal tests data from several human closed patch tests with CAS 683-10-3 demonstrate skin irritation ranging from mild to strong under occlusive conditions even with concentrations as low as 1% (Basketter, 1997; Haskell Laboratory, 1963).

As there is no experimental data available for any of the analogue substances with concentrations greater than 30%, corrosivity has to be assumed for the target substance as worst case for concentrations exceeding 30%.

Studies performed with EC 931-700-2 demonstrated only slight irritation effects on the eye, but not sufficient for a classification according to the criteria of EU Directive 67/548/EEC or Regulation (EC) No 1272/2008. Two studies were available in which C14 and C12 betaine were tested separately (Haynes, 1988a; Haynes, 1988b). An additional study performed at the same time on C10 betaine is also available (Haynes, 1988c). In these studies a decreasing trend of irritation effects was observed with decreasing C-chain length. Furthermore, a number of supporting studies is available in which no information on C-chain length was provided, all demonstrating only slight effects which were mostly reversible within the observation period of 72 hours. Even if not fully reversible within that period the slight characteristics of the effects made it reasonable to assume full reversibility after a slightly longer observation period.

Two studies for eye irritation are available for CAS 68424-94-2. The first one performed with the commercial product (Levenstein, 1979c), the second one with a test material containing 16% solids (Levenstein, 1979d). In the first study, performed with the commercial product (i.e. 30% active, according to the manufacturer), iritis was observed in 2 of 3 animals exceeding the threshold values for a classification as "causing serious eye damage". Since this is the most sensitive study, it was chosen as key study and will be the basis for classification of the target substance. The result is a classification as R41 according to EU Directive 67/548/EEC and as Eye Dam. 1 according to Regulation (EC) No 1272/2008. The second study for CAS 68424-94-2 was done with a test material containing 16% solids. It was also flagged as a key study as it is important for the setting of specific concentration levels according to Regulation (EC) No 1272/2008. In this study corneal opacity was observed which was still sufficient for a classification as Eye Irrit. 2 according to the CLP criteria, but not according to EU Directive 67/548/EEC. In both studies the observed effects were not or at least not fully reversible within the observation period of 7 days.

Three reliable data sources are available for CAS 683-10-3. The study demonstrating the most sensitive effects was performed with 10% (v/v) test material concentration (Jones and Guest, 1987), which induced irritation effects sufficient for a classification as R36 according to the criteria of EU Directive 67/548/EEC and as Eye Irrit. 2 according to the criteria of Regulation (EC) No 1272/2008. The observed effects were characterised by iritis and corneal opacity. This study was chosen as third key study, since it allows to invent specific concentration limits for classification according to EU Directive 67/548/EEC if considered together with the other two key studies for CAS 68424-94-2 (30% and 16%, Levenstein, 1979c and d, respectively). In a worst case approach a classification as R36, irritating to eyes, has to be assumed according to the EU Directive 67/548/EEC for concentrations between the lower generic concentration limit of 5% (due to a classification of the neat substance as corrosive, R34, because of lack of experimental data) and a concentration of 16%, although the study with 16% failed to demonstrate corresponding effects. However, as 10% substance concentration is the lowest concentration tested, which leads to a classification as R36, one has to assume comparable effects in the range of 10% to 16%, as well.

A second study for CAS 683-10-3 was also performed with a concentration of 10% of a commercially available product, but in contrast to the other studies an alternative scoring system was used (Vinardell et al., 1990). According to those criteria the test material at a concentration of 10% would have to be classified as causing serious damage to the eyes (EU Directive 67/548/EEC, R41), but due to the uncommon scoring system this study was not appropriate for assessment. The third reliable study for CAS 683-10-3 was performed with the test substance as supplied, but did not cause irritation sufficient for classification (Haynes, 1987). Therefore, these studies were not further included in the considerations of eye irritation.

Additionally, industrial medical surveillance data was provided for 25 workers of a production plant for CAS 683-10-3 (InfraServ GmbH & Co. KG, 2009). This routine medical check up is performed every 3 years, and the last one was carried out in 2009. The workers were examined for disorders like irritation of the respiratory tract, the eyes, the skin, and allergic disorders or sensitisation related to contact with the test substance. In contrast to the experimental data no observations have been made in these examinations that were related to the test substance.


Justification for selection of skin irritation / corrosion endpoint:
Hazard assessment is conducted by means of read-across from structural analogues. All available studies are adequate and reliable based on the identified similarities in structure and intrinsic properties between source and target substances and overall quality assessment (refer to the endpoint discussion for further details).

Justification for selection of eye irritation endpoint:
Hazard assessment is conducted by means of read-across from structural analogues. All available studies are adequate and reliable based on the identified similarities in structure and intrinsic properties between source and target substances and overall quality assessment (refer to the endpoint discussion for further details).

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Justification for classification or non-classification

The source substances showed irritating effects on rabbit and human skin and on rabbit eyes. The target substance at a concentration of 30% has to be classified for:

Skin irritation according to EU Directive 67/548/EEC (Xi, R38: Irritating to the skin) and Regulation (EC) No 1272/2008 (Skin Irrit. 2, H315: Causes skin irritation).

Eye irritation according to EU Directive 67/548/EEC (Xi, R41: Risk of serious damage to the eyes) and Regulation (EC) No 1272/2008 (Eye Dam. 1, H318: Causes serious eye damage).

Based on the worst case assumption, as there is no experimental data available for test substance concentrations greater than 30%, the neat target substance has to be classified as corrosive according to EU Directive 67/548/EEC (C, R34: Causes burns) and Regulation (EC) No 1272/2008 (Skin Corr. 1B, H314: Causes severe skin burn and eye damage).