Registration Dossier

Administrative data

Description of key information

Skin irritation/corrosion: not irritating (similar to US-FHSA guideline, K, rel. 2).
Eye irritation: not irritating (similar to OECD 405, K, rel.2).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From November 14 to 17, 1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study performed according to US-FHSA guideline. Deviations from standard method: no data on test animals, 24 h exposure instead of 4h, occlusive dressing instead of semi-occlusive, observation at 24 and 72 h only (no 48h scoring), reversibility not assessed during a 14-day observation period. However, since only minimal responses persisted until the 72-h time point (maximum score = 1), the study results can be used for classification purpose (Ref: CLP Guidance). A repeat study is unlikely to show worse effects; therefore, this study was considered sufficiently robust to cover this endpoint.
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study
Qualifier:
according to guideline
Guideline:
other: Section 1500.41 - Hazardous Substances and articles, administration and Enforcement Regulations, Federal Register, Vol. 38, No. 187, P. 27019, 27 September 1973.
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
no
Remarks:
(pre-GLP)
Species:
rabbit
Strain:
not specified
Details on test animals or test system and environmental conditions:
No data
Type of coverage:
occlusive
Preparation of test site:
other: one side intact, the other side abraded
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g on each site
Duration of treatment / exposure:
24 h
Observation period:
24 and 72 h
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: Side of the animals
- Type of wrap if used: Treated areas were covered with gauze patches and an impervious material was wrapped snugly around the trunk of each animal.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No

SCORING SYSTEM: Draize method
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: mean 24 and 72 h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: Intact skin
Irritation parameter:
erythema score
Basis:
animal: #2, #4 & #6
Time point:
other: mean 24 and 72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: intact skin
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: mean 24 and 72 h
Score:
0.5
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: intact skin
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
other: mean 24 and 72 h
Score:
0
Max. score:
4
Remarks on result:
other: intact skin
Irritation parameter:
edema score
Basis:
animal: #1, #4, #5 & #6
Time point:
other: mean 24 and 72 h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible
Remarks:
72 h
Remarks on result:
other: Intact skin
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: mean 24 and 72 h
Score:
0.5
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: intact skin
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: mean 24 and 72 h
Score:
0
Max. score:
4
Remarks on result:
other: intact skin
Irritant / corrosive response data:
- Slight erythema and oedema were observed.
Other effects:
No data

Table 7.3.1/1: Mean irritant/corrosive response data for each animal at each observation time up to removal of animals from the test (intact skin)

 

Score at time point / Reversibility

Erythema

Max. score 4

Oedema

Max. score 4

24 h

1 / 1 / 0/ 1 / 0 / 1

1 / 0 / 0/ 1 / 1 / 1

72 h

0 / 1 / 1/ 1 / 0 / 1

0 / 1 / 0 / 0 / 0 / 0

Average 24h, 72h

0.5 / 1 / 0.5 / 1 / 0 / 1

0.5 / 0.5 / 0 / 0.5 /0.5 / 0.5

Reversibility*)

nc.

Nc.

Average time for reversion

-

-

 

Table 7.3.1/2: Mean irritant/corrosive response data for each animal at each observation time up to removal of animals from the test (abraded skin)

 

Score at time point / Reversibility

Erythema

Max. score 4

Oedema

Max. score 4

24 h

1 / 1 / 0/ 1 / 1 / 1

1 / 0 / 0/ 1 / 0 / 1

72 h

0 / 1 / 1/ 1 / 0 / 1

0 / 1 / 0 / 0 / 0 / 0

Average 24h, 72h

0.5 / 1 / 0.5 / 1 / 0.5 / 1

0.5 / 0.5 / 0 / 0.5 /0 / 0.5

Reversibility*)

nc.

Nc.

Average time for reversion

-

-

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions, the test material is not classified as irritant to the skin according to the Annex VI of the Regulation (EC) No. 1272/2008.
Executive summary:

In a dermal irritation study performed according to US-FHSA guideline, 0.5 g of undiluted test material was dermally applied on the intact or abraded side surface of 6 albino rabbits. Test sites were covered with an occlusive dressing for 24 h. Skin irritation was assessed and scored according to the Draize scale at 24 and 72 h after the removal of the patch.

Under the test conditions, the test material induced slight erythema and oedema. Although reversibility was not assessed, responses were minimal at the 72 -hour time points. According to the CLP Guidance, it is therefore possible to use this study for classification by calculating the mean values for erythema and oedema on the basis of 24 and 72 -h time points.

The individual scores for each animal within 3 scoring times (24, 48 and 72 hours) were 0.5 / 1 / 0.5 / 1 / 0 / 1 for erythema and 0.5 / 0.5 / 0 / 0.5 /0.5 / 0.5 for oedema).

Therefore, the test material is not classified as irritant to the skin according to the Annex VI of the Regulation (EC) No. 1272/2008.

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
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From November 13 to 20, 1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given: comparable to standard OECD test guideline No. 405 with the following deviations: 6 animals tested instead of 3. This deviation does not affect the reliability of this study.
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study
Qualifier:
according to guideline
Guideline:
other: Section 1500.42 - Hazardous Substances and Articles, Administration and Enforcement Regulations, Federal Register, Vol. 38. No. 187, P. 27019, 27 September 1973
Deviations:
no
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
(6 animal tested)
Principles of method if other than guideline:
Not applicable
GLP compliance:
no
Remarks:
(pre-GLP)
Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
Healthy young albino rabbits were used.
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g
Duration of treatment / exposure:
- Eyes of the animals were not rinsed.
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
6 animals
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): No

SCORING SYSTEM: According to the "Illustrated Guide for Grading Eye Irritation by Hazardous Substance"

TOOL USED TO ASSESS SCORE: No data
Irritation parameter:
cornea opacity score
Basis:
animal: #1, #2, #3, #4, #5 & #6
Time point:
other: mean 24, 48 and 72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal: #1, #2, #3, #4, #5 & #6
Time point:
other: mean 24, 48 and 72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
animal: #1 & #4
Time point:
other: mean 24, 48 and 72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal: #1, #3, #5 & #6
Time point:
other: mean 24, 48 and 72 h
Score:
1.33
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: mean 24, 48 and 72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal: #2 & #5
Time point:
other: mean 24, 48 and 72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 5 days
Irritation parameter:
chemosis score
Basis:
animal: #3 & #4
Time point:
other: mean 24, 48 and 72 h
Score:
2.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
other: mean 24, 48 and 72 h
Score:
1.67
Max. score:
4
Reversibility:
fully reversible within: 5 days
Irritant / corrosive response data:
- Animals showed conjunctival reactions (redness, chemosis and discharge) which were reversible within 7 days.
Other effects:
None

Table 7.3.2/1: Eye irritation response data for each animal at each observation time

Score at time point

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

0 / 0 / 0 / 0 / 0 / 0

3 / 3 / 3 / 3 / 3 / 3

3 / 3 / 3 / 3 / 3 / 3

3 / 3 / 3 / 3 / 3 / 3

24 h

0 / 0 / 0 / 0 / 0 / 0

0 / 0 / 0 / 0 / 0 / 0

0 / 0 / 0 / 0 / 0 / 0

3 / 2 / 2 / 3 / 2 / 2

3 / 2 / 3 / 3 / 2 / 3

3 / 2 / 3 / 3 / 3 / 3

48 h

0 / 0 / 0 / 0 / 0 / 0

0 / 0 / 0 / 0 / 0 / 0

0 / 0 / 0 / 0 / 0 / 0

2 / 1 / 1 / 2 / 1 / 1

2 / 1 / 2 / 2 / 1 / 2

2 / 2 / 2 / 2 / 2 / 2

72 h

0 / 0 / 0 / 0 / 0 / 0

0 / 0 / 0 / 0 / 0 / 0

0 / 0 / 0 / 0 / 0 / 0

1 / 1 / 1 / 1 / 1 / 1

1 / 1 / 2 / 2 / 1 / 0

0 / 1 / 1 / 1 / 1 / 0

Day 5

0 / 0 / 0 / 0 / 0 / 0

0 / 0 / 0 / 0 / 0 / 0

0 / 0 / 0 / 0 / 0 / 0

1 / 0 / 1 / 0 / 0 / 0

2 / 0 / 1 / 0 / 0 / 1

0 / 0 / 1 / 0 / 0 / 0

Day 7

0 / 0 / 0 / 0 / 0 / 0

0 / 0 / 0 / 0 / 0 / 0

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 24, 48 and 72 h

0 / 0 / 0 / 0 / 0 / 0

0 / 0 / 0 / 0 / 0 / 0

0 / 0 / 0 / 0 / 0 / 0

2 / 1.33 / 1.33 / 2 / 1.33 / 1.33

2 / 1.33 / 2.33 / 2.33 / 1.33 / 1.67

1.67 / 1.67 / 2 / 2 / 2 / 1.67

Reversibility

 -

 -

-

Completely

reversible

Completely reversible

Completely reversible

Average time (unit) for reversion

-

-

-

7 days

7 days

7 days

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions, the test material induced mild to moderate irritation being reversible within 7 days. Therefore, the test material is not classified as irritant to the eyes.
Executive summary:

In an eye irritation study performed similarly to OECD guideline No. 405, 0.1 g of undiluted test material was instilled into the right eye of 6 albino rabbits while the left eye remained untreated and served as control. The eyes were not rinsed after the instillation of test material. Animals were observed at 1, 24, 48 and 72 h after instillation of test material into eyes and then on Days 5 and 7. The reactions in the conjunctivae (redness, chemosis and discharge), the iris and the cornea (opacity and area involved) were scored according to the grading system outlined in the “Illustrated Guide for Grading Eye Irritation by Hazardous material”.

The calculated mean score for each animal within 3 scoring times (24, 48 and 72 h) were 2 / 1.33 / 1.33 / 2 / 1.33 / 1.33 for redness, 2 / 1.33 / 2.33 / 2.33 / 1.33 / 1.67 for chemosis, 0/0/0/0/0/0 for iris lesions and for corneal opacity.

The observed conjunctival reactions were fully reversible within 7 days. Under the test conditions, the test material is not classified as irritating to the eyes according to the annex VI of the Regulation EC No. 1272/2008 (CLP).

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:

A key study was identified (Biosearch, 1979). This dermal irritation study was performed according to US-FHSA guideline. Deviations from standard OECD method are as follow: 24 h exposure instead of 4h, occlusive dressing instead of semi-occlusive dressing, observation at 24 and 72 h only (no 48h scoring), reversibility not assessed during a 14-day observation period. However, since only minimal responses persisted until the 72 -h time point (maximum score = 1), the study results can be used for classification purpose (Ref: CLP Guidance). A repeat study is unlikely to show worse effects; therefore this study was considered sufficiently robust to cover this endpoint.

Under the test conditions, the test material induced slight erythema and oedema.

The individual scores for each animal within 3 scoring times (24, 48 and 72 hours) were 0.5 / 1 / 0.5 / 1 / 0 / 1 for erythema and 0.5 / 0.5 / 0 / 0.5 /0.5 / 0.5 for oedema).

Therefore, the test material is not classified as irritant to the skin.

Eye irritation:

A key study was identified (Biosearch, 1979, rel.2). This eye irritation study was conducted similarly to OECD Guideline No. 405, with one deviation (6 animals tested instead of 3) that does not affect the reliability of the study.

The calculated mean score for each animal within 3 scoring times (24, 48 and 72 h) were 2 / 1.33 / 1.33 / 2 / 1.33 / 1.33 for redness, 2 / 1.33 / 2.33 / 2.33 / 1.33 / 1.67 for chemosis, 0/0/0/0/0/0 for iris lesions and for corneal opacity.

The conjunctival reactions were fully reversible within 7 days.

Therefore, the test material is not classified as irritant to the eyes.


Justification for selection of skin irritation / corrosion endpoint:
The key study performed on the registered substance in rats was pre-guideline and pre-GLP, but was performed according to US-FHSA guideline. This study was considered sufficiently robust to cover this endpoint.

Justification for selection of eye irritation endpoint:
The key study performed on the registered substance in rats was pre-guideline and pre-GLP, but was performed similarly to OECD Guideline No. 405. This study was considered sufficiently robust to cover this endpoint.

Justification for classification or non-classification

Harmonized classification:

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

Self-classification:

Based on the available data no additional self-classification is proposed regarding skin irritation according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP).

Regarding eye irritation, no additional self-classification is proposed according to the Annex VI of the Regulation (EC) No. 1272/2008 since only 2 out of 6 animals showed a mean score of 2 for conjunctival erythema, and only 3 out of 6 showed a mean score of ≥ 2 for conjunctival oedema (chemosis).

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.