Registration Dossier

Administrative data

Description of key information

Skin: Rabbit. Irritant. Standardized test protocol. Reliability = 2

Eye: Rabbit. Seriously eye damaging. Standardized test protocol. Reliability = 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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
Acceptable, well documented publication/ study report which meets basic scientific principles.
Qualifier:
no guideline followed
Principles of method if other than guideline:
To determine the irritation potential of the test substance, rabbits were exposed dermally to the test substance for 24 hours under occlusive conditions.
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Breeder: W. Ostrop / Meerbusch
The animals were caged single and had "mümmel z" (ssniff / Soest) for diet and water ad libitum.
Temperature 16 - 18 °C, Humidity 40 %
12 h light/12 h dark cycle
Acclimatization period 7 - 14 d.
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
water
Amount / concentration applied:
500 mg in water
Duration of treatment / exposure:
24 h
Observation period:
8 d
Number of animals:
3
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24-72 h
Score:
2.8
Max. score:
4
Reversibility:
other: animals died
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24-72 h
Score:
2.3
Max. score:
3
Reversibility:
other: animals died
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24-72 h
Score:
5.8
Irritant / corrosive response data:
The test substance caused strong erythema and edema after a 24 h treatment. The irritation index of 5.8 gives indication that the substance is strongly irritating to the skin.
Other effects:
72 h after application all animals were dead because of hematuria, splenic congestion, bloody intestine lymph nodes, petechia at the thymus, soaked liver - alltogether, a strong substance-related toxicity was found.

Readings

Animal

Erythema

Edema

Additional findings

24 h

1

4

3

2

2

3

3

2

2

72 h

1

4

3

2

2

2

3

3

1

8 d

1

dead

dead

2

dead

dead

3

dead

dead

Mean

24, 48, 72 h

1

4

3

2

2

2.5

3

2.5

1.5

Mean 24, 48, 72 h

1-3

2.8

2.3

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
The test substacne caused strong erythema and edema after a 24 h treatment. The irritation index was 5.8.
Executive summary:

To determine the irritation potential of the test substance, rabbits were exposed dermally to the test substance for 24 hours under occlusive conditions. The test substance caused strong erythema and edema after a 24 h treatment. The irritation index of 5.8 gives indication that the substance is strongly irritating to the skin.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
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:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
according to
Guideline:
other: Code of Federal Regulations, Title 16, Section 1500.42
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Breeder: W. Ostrop / Meerbusch
The animals were caged single and had "mümmel z" (ssniff / Soest) diet and water ad libitum.
Temperature 16 - 18°C, Humidity 40 %
12 h Light/12 h Dark-Cycle
Acclimatization period 7 - 14 d
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye of the same animal
Amount / concentration applied:
100 µL
Duration of treatment / exposure:
single treatment
Observation period (in vivo):
8 days
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): not rinsed

SCORING SYSTEM: OECD/Draize score
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24-72 h
Score:
1
Max. score:
4
Reversibility:
not reversible
Remarks:
within 8 days
Remarks on result:
other: see table in IUCLID for details
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24-72 h
Score:
1
Max. score:
2
Reversibility:
not reversible
Remarks:
within 8 days
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24-72 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24-72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Irritant / corrosive response data:
The test substance caused a light corneal opacity, iritis, strong erythema and edema of the conjunctivae and increased lacrimation. The clear irritation effects at the eye were only partly reversible within 8 days.

Readings

Animal

Cornea

Iris

Conjunctiva

Additional findings

op

ar

red

ch

di

24 h

1

1

4

1

3

4

3

2

1

4

1

3

4

3

3

1

4

1

3

4

3

48 h

1

1

4

1

3

4

3

2

1

4

1

3

4

3

3

1

4

1

3

4

3

72 h

1

1

4

1

3

4

3

2

1

4

1

3

4

3

3

1

4

1

3

4

3

8 d

1

1

2

1

2

2

3

2

1

2

1

3

2

3

3

1

4

1

3

4

3

Mean

24 -72 h

1

1

4

1

3

4

3

2

1

4

1

3

4

3

3

1

4

1

3

4

3

Mean

24-72 h

1-3

1

4

1

3

4

3

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
Regarding the results of the study, the test substance caused irreversible damage to the eyes.
Executive summary:

The eye irritation potential of the test substance was conducted following methods reported in Code of Federal Regulations, Title 16, Section 1500.42. The test substance (100 µL) was instilled into one eye of 3 rabbits. The other untreated eye served as control. Effects were recorded for up to 8 days after administration. The test substance caused a light corneal opacity, iritis, strong erythema and edema of the conjunctivae and increased lacrimation. The test substance clear irritation effects at the eye were only partly reversible within 8 days.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In a Draize test following a standard test protocol, shaved skin areas of three New Zealand White rabbits received 500 mg of the test substance (purity unknown) in water for 24 hours. During the relevant reading period of 24 -72 hours, the mean erythema score was 2.8 and the mean edema score was 2.3 (scoring system according to the OECD/Draize scheme). The observation period was finished after the 72 hour reading since all animals are were dead because of haematuria, splenic congestion, bloody intestine lymph nodes, petechia at the thymus, soaked liver – all together a strong substance-related toxicity. Under the conditions of the test, the test substance was considered as irritant to the skin.

 

In a study following Fed. Reg. protocol, 100 mg of the unchanged test substance (purity unknown) was administered to the eyes of three New Zealand White rabbits; the eyes were not rinsed. During the relevant reading period 24 -72 hours, the overall scores for corneal opacity, iritis, conjunctivae redness and chemosis were 1.0, 1.0, 3.0 and 4.0, respectively (according to the OECD/Draize scheme). Discharge was also observed (mean score 3.0). Effects were only partly reversible during the observation period; therefore, the test substance was considered as causing serious damage to the eyes.

Justification for classification or non-classification

Based on effects observed in the skin and eye irritation studies, the test substance is classified for skin and eye irritation as Cat 2 (H315: Causes skin irritation) and Cat 1 (H318: Causes serious eye damage), respectively according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.