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Administrative data

Description of key information

Skin irritation: Non irritating (US-FHSA, non-GLP, Rel.2, K).
Eye irritation: Irritating (US-FHSA, non-GLP, Rel. 2, K).

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 July 10 to 13, 1979
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 new study is unlikely to show worse effects; therefore, this study was considered sufficiently robust to cover this endpoint.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
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 and environmental conditions:
No data
Type of coverage:
occlusive
Preparation of test site:
other: one side intact
Vehicle:
unchanged (no vehicle)
Controls:
not required
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 animal's back
- 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: animal #1, #2, #3, #4, #5
Time point:
other: mean 24 and 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72h
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
other: mean 24 and 72 h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 72h
Irritation parameter:
edema score
Basis:
animal: animal #1, #2, #3, #4, #5
Time point:
other: mean 24 and 72 h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 72h
Irritation parameter:
edema score
Basis:
animal #6
Time point:
other: mean 24 and 72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
Slight erythema and edema were observed.
Other effects:
No data

Table 7.3.1/1: Irritant/corrosive response data for each animal 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

24 h

1 / 1 / 1 / 1 / 1 / 1

0 / 0 / 0 / 0 / 0 / 0

72 h

1 / 1 / 1 / 1 / 1 / 0

1 / 1 / 1 / 1 / 1 / 0

Average 24h and 72h

1 / 1 / 1 / 1 / 1 / 0.5

0.5 / 0.5 / 0.5 / 0.5 / 0.5 / 0

Reversibility*)

n.c. (animal #1, #2, #3, #4, #5)

n.c. (animal #1, #2, #3, #4, #5)

Average time for reversion

-

-

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

Interpretation of results:
not classified
Remarks:
Migrated information Slightly irritating 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 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 2 scoring times (24 and 72 hours) were 1 / 1 / 1 / 1 / 1 / 0.5 for erythema and 0.5 / 0.5 / 0.5 / 0.5 / 0.5 / 0 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:
1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study performed according to US-FHSA guideline. Study comparable to test guideline OECD No. 405. No details on test animals and environmental conditions. Effects observed were not fully reversible within 7 days but a beginning of recovery was observed and, based on an expert judgment, a full reversion can be expected within an observation period of 21 days.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
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
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:
TEST ANIMALS: Healthy young adult albino rabbits were used.

IN-LIFE DATES: From July 09 to 16, 1979
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:
Test material was not washed from the eyes.
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
Test material was not washed from the eyes.

SCORING SYSTEM: According to “Illustrated guide for grading eye irritation by hazardous substances”.

TOOL USED TO ASSESS SCORE: No data
Irritation parameter:
cornea opacity score
Basis:
animal: #1, #2 & #6
Time point:
other: mean 24, 48 and 72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal: #3 & #4
Time point:
other: mean 24, 48 and 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
other: mean 24, 48 and 72 h
Score:
1.67
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal: #1, #2
Time point:
other: mean 24, 48 and 72 h
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: mean 24, 48 and 72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #4
Time point:
other: mean 24, 48 and 72 h
Score:
1.33
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #5
Time point:
other: mean 24, 48 and 72 h
Score:
1.67
Max. score:
2
Reversibility:
fully reversible within: 5 days
Irritation parameter:
iris score
Basis:
animal #6
Time point:
other: mean 24, 48 and 72 h
Score:
1.67
Max. score:
2
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal: #1, #2, #3 & #6
Time point:
other: mean 24, 48 and 72 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
other: mean 24, 48 and 72 h
Score:
2.67
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
other: mean 24, 48 and 72 h
Score:
2
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:
3.33
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: mean 24, 48 and 72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: mean 24, 48 and 72 h
Score:
1.67
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
other: mean 24, 48 and 72 h
Score:
2.67
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
other: mean 24, 48 and 72 h
Score:
2.33
Max. score:
4
Reversibility:
fully reversible within: 5 days
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
other: mean 24, 48 and 72 h
Score:
2.67
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritant / corrosive response data:
Animals showed corneal, iridal and conjunctival reactions (redness, chemosis and discharge) which were not reversible in 7 days observation period.
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)

24 h (Day 1)

2 / 2 / 1 / 1 / 2 / 2

3 / 4 / 4 / 4 / 4 / 4

1 / 1 / 1 / 2 / 2 / 2

2 / 2 / 2 / 3 / 2 / 2

4 / 4 / 2 / 3 / 3 / 3

3 / 3 / 3 / 3 / 3 / 3

48 h (Day 2)

2 / 2 / 1 / 1 / 2 / 2

4 / 4 / 4 / 4 / 4 / 4

1 / 1 / 1 / 1 / 2 / 1

2 / 2 / 2 / 3 / 2 / 2

3 / 4 / 1 / 3 / 2 / 3

3 / 3 / 2 / 3 / 3 / 3

72 h (Day 3)

2 / 2 / 1 / 1 / 1 / 2

4 / 4 / 4 / 4 / 4 / 4

1 / 1 / 1 / 1 / 1 / 2

2 / 2 / 2 / 2 / 2 / 2

3 / 4 / 2 / 2 / 2 / 2

3 / 3 / 2 / 2 / 3 / 3

Day 5

1 / 2 / 1 / 1 / 1 / 1

4 / 4 / 4 / 4 / 4 / 4

1 / 1 / 1 / 1 / 0 / 1

2 / 2 / 1 / 1 / 1 / 1

2 / 2 / 1 / 1 / 0 / 1

2 / 2 / 2 / 1 / 1 / 1

Day 7

1 / 1 / 0 / 0 / 0 / 1

4 / 4 / 0 / 0 / 0 / 4

1 / 1 / 0 / 0 / 0 / 1

2 / 1 / 1 / 0 / 0 / 1

2 / 1 / 0 / 0 / 0 / 1

2 / 1 / 0 / 1 / 0 / 1

Average 24, 48 and 72 h

2.00 / 2.00 / 1.00 / 1.00 / 1.67 / 2.00

3.67 / 4.00 / 4.00 / 4.00 / 4.00 / 4.00

1.00 / 1.00 / 1.00 / 1.33 / 1.67 / 1.67

2.00 / 2.00 / 2.00 / 2.67 / 2.00 / 2.00

3.33 / 4.00 / 1.67 / 2.67 / 2.33 / 2.67

3.00 / 3.00 / 2.33 / 2.67 / 3.00 / 3.00

Reversibility

Not reversible

Not reversible

Not reversible

Not

reversible

Not reversible

Not reversible

Average time (unit) for reversion

-

-

-

-

-

-

Interpretation of results:
highly irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions, the test material has a classification of Category 2 (H319: Causes serious eye irritation) according to the Regulation (EC) No. 1272/2008 (CLP).
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. Test material was not washed from the eyes. Animals were observed at 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 “Illustrated guide for grading eye irritation by hazardous substances”.

 

The calculated mean score for each animal within 3 scoring times (24, 48 and 72 h) were 2.00 / 2.00 / 2.00 / 2.67 / 2.00 / 2.00 for redness, 3.33 / 4.00 / 1.67 / 2.67 / 2.33 / 2.67 for chemosis, 1.00 / 1.00 / 1.00 / 1.33 / 1.67 / 1.67 for iris lesions and 2.00 / 2.00 / 1.00 / 1.00 / 1.67 / 2.00 for corneal opacity.

Those scores do not allow to classify the substance for serious eye damage (0/6 rabbits show a mean score per animal of ≥ 3 for corneal opacity and 2/6 animals show a mean score per animal of > 1.5 for iritis). Animals showed corneal and conjunctival reactions (redness, chemosis and discharge) which were not fully reversible within 7 days but the observation period was only 7 days instead of 21 days in current in vivo studies and a beginning of recovery was observed and, based on an expert judgment, a full reversion can be expected within an observation period of 21 days. Therefore, based on the effects observed and the measured scores, the substance is a severe eye irritant.

 

Under the test conditions, the test material has a classification of Category 2 (H319: Causes serious eye irritation) according to the Regulation (EC) No. 1272/2008 (CLP).

 

Although some details on test animals and experimental conditions were missing, this study is considered as acceptable and satisfies the requirement for eye irritation endpoint.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

A key study was identified (Biosearch, 1979, rel.2). 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 new 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 2 scoring times (24 and 72 hours) were 1 / 1 / 1 / 1 / 1 / 0.5 for erythema and 0.5 / 0.5 / 0.5 / 0.5 / 0.5 / 0 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). In this eye irritation study conducted similarly to OECD Guideline No. 405, 0.1 mL of undiluted test material was instilled into the conjunctival sac of one eye of 6 New Zealand White rabbits while the remained untreated eye served as control. The eyes were not rinsed after the instillation of test material. Animals were observed at 24, 48 and 72 h after instillation of test material into eyes and then on Days 5 and 7. The calculated mean score for each animal within 3 scoring times (24, 48 and 72 h) were 2.00 / 2.00 / 2.00 / 2.67 / 2.00 / 2.00 for redness, 3.33 / 4.00 / 1.67 / 2.67 / 2.33 / 2.67 for chemosis, 1.00 / 1.00 / 1.00 / 1.33 / 1.67 / 1.67 for iris lesions and 2.00 / 2.00 / 1.00 / 1.00 / 1.67 / 2.00 for corneal opacity. Those scores do not allow to classify the substance for serious eye damage (0/6 rabbits show a mean score per animal of ≥ 3 for corneal opacity and 2/6 animals show a mean score per animal of > 1.5 for iritis). Animals showed corneal and conjunctival reactions (redness, chemosis and discharge) which were not fully reversible within 7 days but the observation period was only 7 days instead of 21 days in current in vivo studies and a beginning of recovery was observed and, based on an expert judgment, a full reversion can be expected within an observation period of 21 days. Therefore, based on the effects observed and the measured scores, the substance is a severe eye irritant.

Justification for selection of skin irritation / corrosion endpoint:
Only one study available (US-FHSA, non-GLP, Klimisch score=2)

Justification for selection of eye irritation endpoint:
Only one study available (US-FHSA, non-GLP, Klimisch score=2)

Effects on eye irritation: highly irritating

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).

Based on the available data the test material is classified as "Category 2: Causes serious eye irritation" according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP).

No data was available regarding respiratory irritation.