Registration Dossier

Administrative data

Description of key information

Skin irritation/corrosion: read-across, not irritating (OECD 404, GLP, K, rel. 1).

Eye irritation: read-across, not irritating (OECD 405, GLP, K, rel. 1).

Respiratory irritation: no study available.

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:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Further information is included as attachment to section 13.

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source and target substances have similar physico-chemical, (eco)toxicological and environmental fate properties because of their structural similarity.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
The target substance is one of the constituents of the source substance, together with isomers: the target substance is a mono-constituent, individual optical isomer, while the source substance is defined as a multi-constituent, with three pairs of racemate.

3. ANALOGUE APPROACH JUSTIFICATION
The source substance and the target substance are isomers. Based on structural and physico-chemical similarities, it is considered appropriate to read-across data from the source substance.
Skin irritation was not observed in the in vivo test performed on the source substance.
The study design (OECD 404, GLP) is adequate and reliable for the purpose of the prediction based on read-across. The test material used represents the source substance as described in the hypothesis in terms of purity and impurities. The results of the studies are adequate for the purpose of classification and labelling.
Therefore, based on the considerations above, it can be concluded that the result of the Skin Irritation test conducted with the source substance is highly likely to predict the properties of the target substance and is considered as adequate to fulfil the information requirement of Annex VIII, 8.1.

4. DATA MATRIX
Cf. attachment to section 13.
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across: supporting information
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
probability of mild irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
probability of weak irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
probability of weak irritation
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2.7
Max. score:
4
Reversibility:
fully reversible within:
Remarks:
7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
probability of weak irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
probability of weak irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
probability of weak irritation
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
probability of weak irritation
Irritant / corrosive response data:
One hour after the end of the dosing period, erythema varying in degree from slight to well defined was apparent in all 4 rabbits and very slight oedema was noted in 2 of the 4 animals.
24 hours after patch removal erythema and oedema were observed in all 4 rabbits.
At the 72 hour assessment, irritation has entirely subsided in 2 animals. Erythema was slight to moderate in the remaining 2 rabbits.
7 days after the dosing, erythema and oedema were no longer apparent in any of the animal although skin thickening was noted in one of them.
Other effects:
none

Table 7.3.1/1: Irritant/corrosive response data at each observation time up to removal of animals from the test

 

Score at time point / Reversibility

Erythema

Max. score 4

Oedema

Max. score 4

1 h

2/2/2/1

1/0/1/0

24 h

1/1/1/2

2/1/1/1

48 h

2/1/0/3

1/1/0/1

72 h

3/0/0/3

1/0/0/2

Average 24h, 48h, 72h

2/0.7/0.3/2.7

1.3/0.7/0.3/1.3

Reversibility*)

c

c

Average time (day) for reversion**

7 days

7 days

 *) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

**): correspond to the last day for which skin irritation signs in the last animal were observed

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, the source sustance induced a slight irritation being largely reversible within 7 days of dosing.
Therefore the source substance does not require a classification as irritant to the skin according to the Regulation (EC) No. 1272/2008 (CLP) as scores were below 2.3 and to the GHS as only 2 animals out of 4 had scores between 1.5 and 2.3. The same conclusion applies to the target substance.
Executive summary:

In a dermal irritation study performed according to the OECD guideline No. 404, and in compliance with GLP, 0.5 mL of undiluted source substance was dermally applied on the shaved skin of the dorsal surface of the trunk of 4 New Zealand White rabbits. Test sites were covered with a semi-occlusive dressing for 4 hours. Animals were then observed for 7 days for oedema and erythema. 

Skin irritation was assessed and scored according to the Draize scale at 1, 24, 48 and 72 hrs after the removal of the patch and on day 7.

The mean scores over all the animals tested within 3 scoring times (24, 48 and 72 hrs) were 2.0/0.7/0.3/2.7 for erythema and 1.3/0.7/0.3/1.3 for oedema.

Under the test conditions, the soucre substance induced a slight irritation being largely reversible within 7 days of dosing.

Therefore the source substance does not require a classification as irritant to the skin according to the Regulation (EC) No. 1272/2008 (CLP) as scores were below 2.3 and to the GHS as only 2 animals out of 4 had scores between 1.5 and 2.3. The same conclusion applies to the target substance.

This study is considered as acceptable and satisfies the requirement for skin irritation endpoint.

Read-across justification is attached to Iuclid section 13.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 1991-07-09 to 1991-07-16
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study performed according to OECD test guideline No. 404 and in compliance with GLP with minor deviations (age of animals at study initiation not reported). Except for this minor deviation, the study was fully reliable.
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
age of animals at study initiation not reported
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
age of animals at study initiation not reported
Principles of method if other than guideline:
not applicable
GLP compliance:
yes (incl. QA statement)
Remarks:
UK GLP (inspection date: 1990-06-19 / signature date: 1990-10-05)
Specific details on test material used for the study:
- Lot/batch No.: A/S/31635 (lab code)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Ranch Rabbits, Crawley Down, Sussex.
- Age at study initiation: no data
- Weight at study initiation: 2.6-3.0 kg
- Housing: individually in grid bottomed metal cages.
- Diet (e.g. ad libitum): antibiotic free rabbit diet ad libitum (SQC standard rabbits pellets, produced by Special Diets Services, Witham, Essex)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23 °C. On 3 occasions the temperature exceeded this range by 1°C.
- Humidity (%): 59-69 % with the exception of one occasion when a value of 76 % relative humidity was recorded.
- Air changes (per hr): no data
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: no data
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48, and 72 hours after patch removal. Additional examination on day 7.
Number of animals:
4 animals
Details on study design:
TEST SITE
- Area of exposure: dorsal surface of the trunk
- % coverage: 2.5 cm square (6.25 cm2)
- Type of wrap if used: surgical lint held in position with "Elastoplast" elastic adhesive bandage 7.5 cm wide.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): cotton wool soaked in warm water
- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize scale according to OECD guideline No. 404
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
probability of mild irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
probability of weak irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
probability of weak irritation
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2.7
Max. score:
4
Reversibility:
fully reversible within:
Remarks:
7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
probability of weak irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
probability of weak irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
probability of weak irritation
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
probability of weak irritation
Irritant / corrosive response data:
One hour after the end of the dosing period, erythema varying in degree from slight to well defined was apparent in all 4 rabbits and very slight oedema was noted in 2 of the 4 animals.
24 hours after patch removal erythema and oedema were observed in all 4 rabbits.
At the 72 hour assessment, irritation has entirely subsided in 2 animals. Erythema was slight to moderate in the remaining 2 rabbits.
7 days after the dosing, erythema and oedema were no longer apparent in any of the animal although skin thickening was noted in one of them.
Other effects:
none

Table 7.3.1/1: Irritant/corrosive response data at each observation time up to removal of animals from the test

 

Score at time point / Reversibility

Erythema

Max. score 4

Oedema

Max. score 4

1 h

2/2/2/1

1/0/1/0

24 h

1/1/1/2

2/1/1/1

48 h

2/1/0/3

1/1/0/1

72 h

3/0/0/3

1/0/0/2

Average 24h, 48h, 72h

2/0.7/0.3/2.7

1.3/0.7/0.3/1.3

Reversibility*)

c

c

Average time (day) for reversion**

7 days

7 days

 *) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

**): correspond to the last day for which skin irritation signs in the last animal were observed

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, the test material induced a slight irritation being largely reversible within 7 days of dosing.
Therefore the test material does not require a classification as irritant to the skin according to the Regulation (EC) No. 1272/2008 (CLP) as scores were below 2.3 and to the GHS as only 2 animals out of 4 had scores between 1.5 and 2.3.
Executive summary:

In a dermal irritation study performed according to the OECD guideline No. 404, and in compliance with GLP, 0.5 mL of undiluted test material was dermally applied on the shaved skin of the dorsal surface of the trunk of 4 New Zealand White rabbits. Test sites were covered with a semi-occlusive dressing for 4 hours. Animals were then observed for 7 days for oedema and erythema. 

Skin irritation was assessed and scored according to the Draize scale at 1, 24, 48 and 72 hrs after the removal of the patch and on day 7.

The mean scores over all the animals tested within 3 scoring times (24, 48 and 72 hrs) were 2.0/0.7/0.3/2.7 for erythema and 1.3/0.7/0.3/1.3 for oedema.

Under the test conditions, the test material induced a slight irritation being largely reversible within 7 days of dosing.

Therefore the test material does not require a classification as irritant to the skin according to the Regulation (EC) No. 1272/2008 (CLP) as scores were below 2.3 and to the GHS as only 2 animals out of 4 had scores between 1.5 and 2.3.

This study is considered as acceptable and satisfies the requirement for skin irritation endpoint.

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
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Further information is included as attachment to section 13.

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source and target substances have similar physico-chemical, (eco)toxicological and environmental fate properties because of their structural similarity.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
The target substance is one of the constituents of the source substance, together with isomers: the target substance is a mono-constituent, individual optical isomer, while the source substance is defined as a multi-constituent, with three pairs of racemate.

3. ANALOGUE APPROACH JUSTIFICATION
The source substance and the target substance are isomers. Based on structural and physico-chemical similarities, it is considered appropriate to read-across data from the source substance.
Eye irritation was not observed in the in vivo test performed on the source substance.
The study design (OECD 405, GLP) is adequate and reliable for the purpose of the prediction based on read-across. The test material used represents the source substance as described in the hypothesis in terms of purity and impurities. The results of the studies are adequate for the purpose of classification and labelling.
Therefore, based on the considerations above, it can be concluded that the result of the Eye Irritation test conducted with the source substance is highly likely to predict the properties of the target substance and is considered as adequate to fulfil the information requirement of Annex VIII, 8.2.

4. DATA MATRIX
Cf. attachment to section 13.
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across: supporting information
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal: #1 and #4
Time point:
24/48/72 h
Score:
0.7
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
probability of weak irritation
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Remarks on result:
probability of weak irritation
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
probability of weak irritation
Irritation parameter:
chemosis score
Basis:
animal: #2 and #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
probability of weak irritation
Irritation parameter:
cornea opacity score
Basis:
animal: #1, #2, #3 and #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal: #1, #2, #3 and #4
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
One hour after dosing, some discharge and chemosis and definite conjunctival redness (grade 2-3) were noted in all 4 animals. Between 24 and 48 hours the irritation was reduced with only slight chemosis and/or redness in some animals. At 72 hours, no signs of irritation were detected in any animals. No corneal or iridial irritation occurred in any animal during the study.
Other effects:
No other effect

Table 7.3.2/1: Mean irritant/corrosive response data of 4 animals at each observation time up to removal from the test

 

Score at time point / Reversibility

Cornea

Iris

(/2)

Conjunctivae

Opacity

(/4)

Area

(/4)

Redness

(/3)

Chemosis

(/4)

Discharge

(/3)

1 h

0

0

0

2.25

1.50

1.25

24 h

0

0

0

0.75

0.50

0

48 h

0

0

0

0.50

0.25

0

72 h

0

0

0

0.00

0.00

0

Reversibility*)

-

-

-

c.

c.

c.

Average time (unit) for reversion

-

-

-

72 h

72 h

24 h

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

Table 7.3.2/2: Individual irritant/corrosive response data at each observation time up to removal from the test

 

Score at time point / Reversibility

Cornea

Iris

(/2)

Conjunctivae

Opacity

(/4)

Area

(/4)

Redness

(/3)

Chemosis

(/4)

Discharge

(/3)

1 h

0 / 0 / 0 / 0

0 / 0 / 0 / 0

0 / 0 / 0 / 0

3 / 2 / 2 / 2

2 / 1 / 1 / 2

1 / 1 / 1 / 2

24 h

0 / 0 / 0 / 0

0 / 0 / 0 / 0

0 / 0 / 0 / 0

1 / 1 / 0 / 1

1 / 0 / 0 / 1

0 / 0 / 0 / 0

48 h

0 / 0 / 0 / 0

0 / 0 / 0 / 0

0 / 0 / 0 / 0

1 / 0 / 0 / 1

1 / 0 / 0 / 0

0 / 0 / 0 / 0

72 h

0 / 0 / 0 / 0

0 / 0 / 0 / 0

0 / 0 / 0 / 0

0 / 0 / 0 / 0

0 / 0 / 0 / 0

0 / 0 / 0 / 0

Average 24h, 48h, 72h

0 / 0 / 0 / 0

0 / 0 / 0 / 0

0 / 0 / 0 / 0

0.7 / 0.3 / 0.0 / 0.7

0.7 / 0.0 / 0.0 / 0.3

0 / 0 / 0 / 0

Reversibility*)

-

-

-

 c.

c. 

c. 

Average time (unit) for reversion

-

-

-

 72 h

72 h 

24 h 

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, the source substance is not classified as irritating to eyes according to the criteria of the Regulation (EC) No 1272/2008 (CLP) and of the GHS. The same conclusion applies to the Target substance.
Executive summary:

In an eye irritation study performed according to the OECD guideline No. 405, and in compliance with GLP, 0.1 mL of undiluted source substance was instilled into the right eye of 4 female New Zealand White Rabbits. The eyes were not rinsed after the instillation of the test item. The left eye of each rabbit served as control. Animals were observed at 1, 24, 48 and 72 hours after dosing under a standard light source. The reactions in the conjunctiva (redness, chemosis and discharge), the iris and the cornea (opacity and area involved) were scored according to the Draize scale. 

 

The calculated mean score for each individual lesion for all animals within 3 scoring times (24, 48 and 72 hrs) were as follows: 0.3 for chemosis; 0.4 for redness; 0.0 for discharge, iris and corneal lesions.

The calculated mean score for each individual lesion for each individual animal within 3 scoring times (24, 48 and 72 hrs) were as follows: 0.7/0.0/0.0/0.3 for chemosis; 0.7/0.3/0.0/0.7 for redness; 0/0/0/0 for discharge, iris and corneal lesions.

The effects observed were all reversible within 72 hours.

 

Under the test conditions, the source substance is not classified as irritating to eyes according to the criteria of the Regulation (EC) No. 1272/2008 (CLP) and of the GHS. The same conclusion applies to the Target substance.

This study is considered as acceptable and satisfies the requirement for eye irritation endpoint.

Read-across justification is attached to Iuclid section 13.

 

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 1991-08-20 to 1991-08-30
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study performed according to OECD test guideline No. 405 and in compliance with GLP with minor deviations (age of animals at study initiation not reported). Except for this minor deviation, the study was fully reliable.
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
age of animals at study initiation not reported
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
age of animals at study initiation not reported
Principles of method if other than guideline:
not applicable
GLP compliance:
yes (incl. QA statement)
Remarks:
UK GLP compliance programme (inspection date: 1990-06-19 / signature date: 1990-10-05)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Ranch Rabbits, Crawley Down, Sussex.
- Age at study initiation: no data
- Weight at study initiation: 2.8-3.2 kg
- Housing: individually in grid bottomed metal cages.
- Diet (e.g. ad libitum): antibiotic free rabbit diet ad libitum (SQC Stanrab, produced by Special Diets Services, Witham, Essex)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-21 °C.
- Humidity (%): 59-69 % with the exception of one occasion when a value of 76 % relative humidity was recorded.
- Air changes (per hr): no data
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: no data
Vehicle:
unchanged (no vehicle)
Controls:
other: the contralateral eye remained untreated
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): not applicable

VEHICLE
Not applicable
Duration of treatment / exposure:
The eye was not rinsed after the instillation of the test item.
Observation period (in vivo):
Examination made 1, 24, 48 and 72 hours following instillation
Number of animals or in vitro replicates:
4 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): not applicable
- Time after start of exposure: not applicable

SCORING SYSTEM: Draize scale according to the OECD guideline No. 405

TOOL USED TO ASSESS SCORE: standard light source designed to comply with the requirements of BS 950 Part 1 (Artificial Daylight for the Assessment of Colour)
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal: #1 and #4
Time point:
24/48/72 h
Score:
0.7
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
probability of weak irritation
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Remarks on result:
probability of weak irritation
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
probability of weak irritation
Irritation parameter:
chemosis score
Basis:
animal: #2 and #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
probability of weak irritation
Irritation parameter:
cornea opacity score
Basis:
animal: #1, #2, #3 and #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal: #1, #2, #3 and #4
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
One hour after dosing, some discharge and chemosis and definite conjunctival redness (grade 2-3) were noted in all 4 animals. Between 24 and 48 hours the irritation was reduced with only slight chemosis and/or redness in some animals. At 72 hours, no signs of irritation were detected in any animals. No corneal or iridial irritation occurred in any animal during the study.
Other effects:
No other effect

Table 7.3.2/1: Mean irritant/corrosive response data of 4 animals at each observation time up to removal from the test

 

Score at time point / Reversibility

Cornea

Iris

(/2)

Conjunctivae

Opacity

(/4)

Area

(/4)

Redness

(/3)

Chemosis

(/4)

Discharge

(/3)

1 h

0

0

0

2.25

1.50

1.25

24 h

0

0

0

0.75

0.50

0

48 h

0

0

0

0.50

0.25

0

72 h

0

0

0

0.00

0.00

0

Reversibility*)

-

-

-

c.

c.

c.

Average time (unit) for reversion

-

-

-

72 h

72 h

24 h

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

Table 7.3.2/2: Individual irritant/corrosive response data at each observation time up to removal from the test

 

Score at time point / Reversibility

Cornea

Iris

(/2)

Conjunctivae

Opacity

(/4)

Area

(/4)

Redness

(/3)

Chemosis

(/4)

Discharge

(/3)

1 h

0 / 0 / 0 / 0

0 / 0 / 0 / 0

0 / 0 / 0 / 0

3 / 2 / 2 / 2

2 / 1 / 1 / 2

1 / 1 / 1 / 2

24 h

0 / 0 / 0 / 0

0 / 0 / 0 / 0

0 / 0 / 0 / 0

1 / 1 / 0 / 1

1 / 0 / 0 / 1

0 / 0 / 0 / 0

48 h

0 / 0 / 0 / 0

0 / 0 / 0 / 0

0 / 0 / 0 / 0

1 / 0 / 0 / 1

1 / 0 / 0 / 0

0 / 0 / 0 / 0

72 h

0 / 0 / 0 / 0

0 / 0 / 0 / 0

0 / 0 / 0 / 0

0 / 0 / 0 / 0

0 / 0 / 0 / 0

0 / 0 / 0 / 0

Average 24h, 48h, 72h

0 / 0 / 0 / 0

0 / 0 / 0 / 0

0 / 0 / 0 / 0

0.7 / 0.3 / 0.0 / 0.7

0.7 / 0.0 / 0.0 / 0.3

0 / 0 / 0 / 0

Reversibility*)

-

-

-

 c.

c. 

c. 

Average time (unit) for reversion

-

-

-

 72 h

72 h 

24 h 

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, the test material is not classified as irritating to eyes according to the criteria of the Regulation (EC) No 1272/2008 (CLP) and of the GHS.
Executive summary:

In an eye irritation study performed according to the OECD guideline No. 405, and in compliance with GLP, 0.1 mL of undiluted test material was instilled into the right eye of 4 female New Zealand White Rabbits. The eyes were not rinsed after the instillation of the test item. The left eye of each rabbit served as control. Animals were observed at 1, 24, 48 and 72 hours after dosing under a standard light source. The reactions in the conjunctiva (redness, chemosis and discharge), the iris and the cornea (opacity and area involved) were scored according to the Draize scale. 

 

The calculated mean score for each individual lesion for all animals within 3 scoring times (24, 48 and 72 hrs) were as follows: 0.3 for chemosis; 0.4 for redness; 0.0 for discharge, iris and corneal lesions.

The calculated mean score for each individual lesion for each individual animal within 3 scoring times (24, 48 and 72 hrs) were as follows: 0.7/0.0/0.0/0.3 for chemosis; 0.7/0.3/0.0/0.7 for redness; 0/0/0/0 for discharge, iris and corneal lesions.

The effects observed were all reversible within 72 hours.

 

Under the test conditions, the test material is not classified as irritating to eyes according to the criteria of the Regulation (EC) No. 1272/2008 (CLP) and of the GHS.

This study is considered as acceptable and satisfies the requirement for eye irritation endpoint.

 

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation/corrosion:

A key study was identified on a source substance (Toxicol, 1992, rel. 1). This dermal irritation study was performed according to the OECD guideline No. 404, and in compliance with GLP. The mean scores over all the 4 animals tested within 3 scoring times (24, 48 and 72 hrs) were 2.0/0.7/0.3/2.7 for erythema and 1.3/0.7/0.3/1.3 for oedema. Under the test conditions, the source substance induced a slight irritation being largely reversible within 7 days of dosing and therefore does not require classification for skin irritation.

The same conclusion applies to the target substance.

(see Iuclid section 13 for read-across justification).

Eye irritation:

A key study was identified on a source substance (Toxicol, 1992, rel. 1). This eye irritation study was performed according to the OECD guideline No. 405, and in compliance with GLP. The calculated mean score for each individual lesion for all 4 animals within 3 scoring times (24, 48 and 72 hrs) were as follows: 0.3 for chemosis; 0.4 for redness; 0.0 for discharge, iris and corneal lesions. The calculated mean score for each individual lesion for each individual animal within 3 scoring times (24, 48 and 72 hrs) were as follows: 0.7/0.0/0.0/0.3 for chemosis; 0.7/0.3/0.0/0.7 for redness; 0/0/0/0 for discharge, iris and corneal lesions. The effects observed were all reversible within 72 hours. The source substance does not require classification for eye irritation.

The same conclusion applies to the target substance.

(see Iuclid section 13 for read-across justification).

Justification for classification or non-classification

Harmonised classification:

The substance has no harmonised classification according to the Regulation (EC) No. 1272/2008 (CLP).

Self-classification:

Based on the available information on the source substance, no additional self-classification is proposed regarding both skin and eye irritation according to the CLP as scores were below 2.3 and to the GHS as only 2 animals out of 4 had scores between 1.5 and 2.3.

Based on the available information on the source substance, no additional self-classification is proposed regarding eye irritation according to the CLP and to the GHS.

No data was available regarding respiratory irritation, however the substance not being classified for skin and eye irritation, no classification is expected for respiratory irritation.