Registration Dossier

Administrative data

Description of key information

The source substance is non-irritant to rabbit skin but is severely irritating to rabbit eyes.

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:
supporting study
Study period:
1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
no
Specific details on test material used for the study:
FAT 41001/C
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH-4414 Fuellinsdorf
- Age at study initiation:12 - 14 weeks
- Weight at study initiation: 2320-2560 g
- Housing: Animals were housed individually in metal cages.
- Diet (e.g. ad libitum): Rabbit food, NAFAG, No. 814 Tox, NAFAG AG, Gossau, SG (Switzerland), ad libitum.
- Water (e.g. ad libitum): Water were provided ad libitum.


ENVIRONMENTAL CONDITIONS
- Temperature (°C):20±3
- Humidity (%): 30-70
- Air changes (per hr):approximately 15 air changes/h
- Photoperiod (hrs dark / hrs light): 12 hours light/day
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48, 72 hours
Number of animals:
3 males
Details on study design:
SCORING SYSTEM:
The index of primary cutaneous irritation was calculated as follows:
- the scores obtained for erythema and edema at 1 hour, 24, 48 and 72 hours after removal of the patch, on the 3 rabbits examined, are summed up
- the sums of total edema and erythema were divided by 12 when all the animals survived.
- the score obtained is defined as the "index of primary cutaneous irritation".
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
7 d
Score:
0.66
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of 3 rabbits
Time point:
24/48/72 h
Score:
0.11
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
mean
Remarks:
of 3 rabbits
Time point:
24/48/72 h
Score:
0.11
Max. score:
4
Reversibility:
fully reversible
Irritant / corrosive response data:
The animals showed a normal body weiqht development.
No other reactions to treatment were recorded durinq the whole observation period.
Other effects:
None

None

Interpretation of results:
GHS criteria not met
Conclusions:
It can be concluded that the test substance is not an irritant or corrosive when applied to the rabbit skin according to GHS criteria; there was a clear tendency of recovery towards the end of the observation period.
Executive summary:

Acute dermal skin irritation/corrosion study in the rabbits was carried out according to OECD guideline 404.

According to the criteria of the study, the test substance was slightly irritant with an overall irritation score of 0.66. According to GHS criteris, the test substance is not an irritant or corrosive when applied to the rabbit skin, There was a clear tendency of recovery towards the end of the observation period.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
no
Specific details on test material used for the study:
FAT 41001/D
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH-4414 Fuellinsdorf
- Age at study initiation:12 - 14 weeks
- Weight at study initiation: 2000-2260 g
- Housing: Animals were housed individually in metal cages.
- Diet (e.g. ad libitum): Rabbit food, NAFAG, No. 814 Tox, NAFAG AG, Gossau, SG (Switzerland), ad libitum.
- Water (e.g. ad libitum): Water were provided ad libitum.


ENVIRONMENTAL CONDITIONS
- Temperature (°C):20±3
- Humidity (%): 30-70
- Air changes (per hr):approximately 15 air changes/h
- Photoperiod (hrs dark / hrs light): 12 hours light/day
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48, 72 hours
Number of animals:
3 females
Details on study design:
SCORING SYSTEM:
After removal of the dressings the skin reaction was assessed on the basis of an evaluation scheme, (cf. Table 1), after 1, 24, 48, 72 hours and during the following observation period.
The score obtained is defined as the "index of primary cutaneous irritation".

INDEX CLASSIFICATION
<0.5 non irritant
0.6 - 3.0 slightly irritant
3.1 - 5.0 irritant
5.1 - 8.0 severely irritant
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 7 days
Score:
0.33
Max. score:
8
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: only 1 animal could be assessed due to strong colouring of the skin
Irritation parameter:
edema score
Basis:
mean
Remarks:
of 3 rabbits
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
The animals showed a normal body weight development.
As in two of three rabbits scoring was not possibile due to intensive blue staining by the test compound, the scoring was performed according the values for edema only.
Interpretation of results:
GHS criteria not met
Conclusions:
It can be concluded that the test substance is non-irritant and not corrosive when applied to the rabbit skin; the test was terminated after 3 observation days.
Executive summary:

Acute dermal skin irritation/corrosion study in the rabbits was carried out in accordance with OECD guideline 404. The animals showed a normal body weight development.

As in two of three rabbits scoring was not possibile due to intensive blue staining by the test compound, the evaluation was performed with the values for edema only.

It can be concluded that the test substance is non-irritant and not corrosive when applied to the rabbit skin; the test was terminated after 3 observation days.

Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that the source and the target substance have very similar physicochemical and (eco)toxicological properties because their chemical structures are nearly identical. An analogue approach has thus been employed. The target substance is the meta-isomer of the dye Reactive Blue 049, where the sulphonate group is bound at the meta-position of the aminobenzene moiety. The source chemical is the reaction mass of both the meta-isomer and the para-isomer of Reactive Blue 049.
The presence of sulphonate groups make both dyes highly water soluble and therefore less critical for human health and environmental issues. Based on their chemical similarity, similar properties are expected in both humans and the environment.

2. SOURCE AND TARGET CHEMICAL(S)
Source: Reactive Blue 49 meta/para (CAS# 72214-18-7 / EC# 276-481-8)
Target: Reactive Blue 49 meta (CAS# 72927-99-2 / EC# 277-040-2)

3. ANALOGUE APPROACH JUSTIFICATION
see attachment under 4.2 Melting point / freezing point
Reason / purpose:
read-across source
Reason / purpose:
read-across source
GLP compliance:
no
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 7 days
Score:
0.33
Max. score:
8
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: only 1 animal could be assessed due to strong colouring of the skin
Irritation parameter:
edema score
Basis:
mean
Remarks:
of 3 rabbits
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
The animals showed a normal body weight development.
As in two of three rabbits scoring was not possibile due to intensive blue staining by the test compound, the scoring was performed according the values for edema only.
Interpretation of results:
GHS criteria not met
Conclusions:
It can be concluded that the test substance is non-irritant and not corrosive when applied to the rabbit skin; the test was terminated after 3 observation days.
Executive summary:

Acute dermal skin irritation/corrosion study in the rabbits was carried out in accordance with OECD guideline 404. The animals showed a normal body weight development. As in two of three rabbits scoring was not possibile due to intensive blue staining by the test compound, the evaluation was performed with the values for edema only. It can be concluded that the test substance is non-irritant and not corrosive when applied to the rabbit skin; the test was terminated after 3 observation days.

The structurally related target substance will show the same behaviour and will therefore be non-irritant to skin as well.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that the source and the target substance have very similar physicochemical and (eco)toxicological properties because their chemical structures are nearly identical. An analogue approach has thus been employed. The target substance is the meta-isomer of the dye Reactive Blue 049, where the sulphonate group is bound at the meta-position of the aminobenzene moiety. The source chemical is the reaction mass of both the meta-isomer and the para-isomer of Reactive Blue 049.
The presence of sulphonate groups make both dyes highly water soluble and therefore less critical for human health and environmental issues. Based on their chemical similarity, similar properties are expected in both humans and the environment.

2. SOURCE AND TARGET CHEMICAL(S)
Source: Reactive Blue 49 meta/para (CAS# 72214-18-7 / EC# 276-481-8)
Target: Reactive Blue 49 meta (CAS# 72927-99-2 / EC# 277-040-2)

3. ANALOGUE APPROACH JUSTIFICATION
see attachment under 4.2 Melting point / freezing point
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
1.56
Max. score:
2
Reversibility:
fully reversible within: 21 days
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
3.67
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritant / corrosive response data:
In two rabbits the eyes were recovered after 21 days. In one rabbit slight reddening and cornea turbidity was still observed on Day 21.
Other effects:
The animals showed a normal body weight development.
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
The test item showed irritating effects to eyes when applied to the rabbit eye mucosa
Executive summary:

In a test performed according to OECD test guideline 405, the test substance was assessed for eye irritation potential. Three male rabbits were treated with 0.1 g of test mateial and observed over 21 days. Under the conditions of the present experiment the test substance was found to be severely irritant when applied to the rabbit eye mucosa.

The structurally related target substance will show the same behaviour and will therefore be classified as a severe eye irritant.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
no
Specific details on test material used for the study:
FAT 41001/C
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH-4414 Fuellinsdorf
- Age at study initiation: 12 - 14 weeks
- Weight at study initiation: ca 2 kg
- Housing: Animals were housed individually in metal cages.
- Diet (e.g. ad libitum):Rabbit food, NAFAG, No. 814 Tox, NAFAG AG, Gossau, SG (Switzerland), ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±3
- Humidity (%):30-70
- Air changes (per hr): 15 air changes/h.
- Photoperiod (hrs dark / hrs light): 12 hours light/day
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
Duration of treatment / exposure:
1 hour
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3 males
Details on study design:
Application of the test article:
0.1 ml of the test article was placed into the conjunctival sac of the right eye of each animal, after gently pulling away the lower lid from the eyeball. The lids were then held together for about one second in order to prevent loss of the test material. The left eye remained untreated and served as the control.
SCORING SYSTEM:
The irritating and/or corrosive potential of the test article (theoretical range: non-irritant - extremely irritant) was assessed on the basis of the maximum irritant effect observed
- in one or several of the ocular tissues (conjunctiva, iris, cornea), observed over the range of observation time
- in one or more animals and taking into account the reversibility of the effect.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0.2
Max. score:
3
Reversibility:
fully reversible within: 72 h
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
The animals showed a normal body weight development.
No other reactions to treatment were recorded during the whole observation period.
Interpretation of results:
GHS criteria not met
Conclusions:
According to GHS criteria, the liquid formulation of Reactive Blue 49 (meta/para) was not irritating to the rabbit eye.
Executive summary:

Under the conditions of the present experiment the test susbtance was not irritant and not corrosive when applied to the rabbit eye mucosa according to CLP criteria. All effects seen, were recoved after 72 hours.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
no
Specific details on test material used for the study:
FAT 41001/D
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH-4414 Fuellinsdorf
- Age at study initiation:1800-1990 g
- Weight at study initiation:12 - 14 weeks
- Housing: Animals were housed individually in metal cages.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C):20±3
- Humidity (%):30-70
- Air changes (per hr):approximately 15 air changes/h.
- Photoperiod (hrs dark / hrs light):12 hours light/day
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g
Duration of treatment / exposure:
1 hour
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
3 males
Details on study design:
SCORING SYSTEM:
The irritating and/or corrosive potential of the test article (theoretical range: non-irritant - extremely irritant) was assessed on the basis of the maximum irritant effect observed
- in one or several of the ocular tissues (conjunctiva, iris, cornea), observed over the range of observation time
- in one or more animals and taking into account the reversibility of the effect.

TOOL USED TO ASSESS SCORE: hand-slit lamp
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
1.56
Max. score:
2
Reversibility:
fully reversible within: 21 days
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
3.67
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritant / corrosive response data:
In two rabbits the eyes were recovered after 21 days. In one rabbit slight reddening and cornea turbidity was still observed on Day 21.
Other effects:
The animals showed a normal body weight development.
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
The test item showed irritating effects to eyes when applied to the rabbit eye mucosa
Executive summary:

In a test performed according to OECD test guideline 405, the test substance was assessed for eye irritation potential. Three male rabbits were treated with 0.1 g of test mateial and observed over 21 days.

Under the conditions of the present experiment the test substance was found to be severely irritant when applied to the rabbit eye mucosa.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The following information is available for the source substance:

A key study was carried out to determine the acute dermal skin irritation/corrosion potential in the rabbits in accordance with OECD guideline 404. The animals showed a normal body weight development.

It can be concluded, that Reactive Blue 49 (purity: 78.8%) is non-irritant and not corrosive when applied to the rabbit skin; the test was terminated after 3 observation days.

A supporting study was carried out to determine the acute dermal skin irritation/corrosion potential in the rabbits according to OECD guideline 404.

Under the conditions of the present experiment, the liquid preparation of Reactive Blue 49 (purity: 26.1 % AS.) was found to be slightly irritant and not corrosive when applied to the rabbit skin according to the study criteria. There was a clear tendency of recovery towards the end of the observation period of 7 days. The calculated dermal irritation index was 0.66. According to GHS criteria, the test substance is not irritating.

A key study was carried out to determine the acute eye irritation/corrosion potential in the rabbits in accordance with OECD guideline 405. Severe eye effects were seen during the study. In two rabbits all signs of irritation were reversed after the 21 day observation period. One rabbit eye still showed slight reddening and cornea opacity on Day 21. Under the conditions of the present experiment Reactive Blue 49 (purity: 78.8%) was found to cause irreversible eye damage when applied to the rabbit eye mucosa.

Under the conditions of the present supporting study the liquid preparation of Reactive Blue 49 (purity: 26.1 % AS) was found to be slightly irritant and not corrosive when applied to the rabbit eye mucosa. There was a clear tendency of recovery towards the end of the observation period of 7 days.

Justification for classification or non-classification

The source substance is non-irritant to rabbit skin but is severely irritating to rabbit eyes. It is anticipated that the structurally related target substance will show the same behaviour. Therefore it will be classified according to CLP with Eye Dam 1 H318.