Registration Dossier

Administrative data

Description of key information

Skin irritation, rabbit: corrosive

Eye irritation, rabbit: severe damages to the eye

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
Qualifier:
no guideline followed
Principles of method if other than guideline:
- Principle of test: The test substance was assessed for skin irritation in rabbits.
- Short description of test conditions: Two animals were exposed to 500 mg of the test substance on the flank for 24 h. Animals were observed for 7 days.
- Parameters analysed / observed: reddening and swelling
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 3 - 4 kg
- Housing: individually
Type of coverage:
not specified
Preparation of test site:
not specified
Vehicle:
not specified
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 g
Duration of treatment / exposure:
24 h
Observation period:
7 days
Number of animals:
2
Details on study design:
TEST SITE
- Area of exposure: flank
- Type of wrap if used: Band-Aids

REMOVAL OF TEST SUBSTANCE
- Washing: with water, soap and vegetable oil
- Time after start of exposure: 24 h

OBSERVATION TIME POINTS
directly after test substance removal, after 24 and 48 h and after 7 days

SCORING SYSTEM:
- Method of calculation: Draize scoring system
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48 h
Score:
2.5
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48 h
Score:
2.5
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritant / corrosive response data:
Necrotic changes of the skin in the area of treatment were observed on the first, second and seventh day of the observation period.

Table 1: Grades for Dermal Irritation

Animal no.

Erythema

Edema

0 h*

24 h

48 h

7 d

0 h*

24 h

48 h

7 d

41

4

4

4

4

4

3

2

2

51

4

4

4

4

4

3

2

2

* directly after test substance removal

Interpretation of results:
Category 1 (corrosive) based on GHS criteria
Conclusions:
The findings clearly indicate that the test compound caused irreversible damage to the skin which in terms of classification according to Regulation (EC) No 1272/2008 implies classification as Skin Corr. 1, H314.
Executive summary:

A study for dermal irritation in the rabbit was conducted with the test substance. Two New Zealand White rabbits received 0.5 g of the test substance to the flank for 24 h. After exposure duration the test substance was removed by washing with water, soap and vegetable oil. The treated skin surface was examined directly after test substance removal, at 24 and 48 h as well as at 7 days after removal. The Draize scale was used for scoring the skin reactions. Deep reddening (erythema score 4) was noted in both animals at all reading time points. Both animals exhibited severe swelling at the application site (score 4) after test substance removal which was not fully reversible up to the end of the 7-day observation period (score 3 at 24 h, score 2 at 48 h and 7 days after test substance removal in both animals). Necrotic changes of the skin in the area of treatment were observed on the first, second and seventh day of the observation period. Thus, under the conditions of this study, the test substance is corrosive to the skin which in terms of classification according to Regulation (EC) No 1272/2008 implies classification as Skin Corr. 1, H314: Causes severe skin burns and eye damage.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

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:
no guideline followed
Principles of method if other than guideline:
- Principle of test: The test substance was assessed for mucous membrane irritation in rabbits.
- Short description of test conditions: The test substance was applied into the conjunctiva sack of two animals (50 mg). Animals were observed for 7 days.
- Parameters analysed / observed: reddening and swelling of conjunctiva, corneal opacity, iritis
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 3 - 4 kg
- Housing: individually
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.05 g
Duration of treatment / exposure:
single application without washing
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
2
Details on study design:
SCORING SYSTEM: Draize scoring system
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.67
Max. score:
2
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.33
Max. score:
3
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.67
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.33
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritant / corrosive response data:
An increasing amount of discharge from the eye was observed during the entire period of observation after the examination.

Table 1:Results of eye irritation study

Rabbit No.

Organ investigated

hours/days after application and rinsing

1 h

24 h

48 h

72 h

7 d

1

Cornea*

2/4

2/4

2/4

2/4

2/4

Iris

1

1

2

2

2

Conjunctivae (redness)

2

1

2

3

2

Conjunctivae (swelling)

2

1

2

2

2

2

Cornea*

3/4

4/3

4/3

4/3

4/3

Iris

2

2

2

2

2

Conjunctivae (redness)

3

2

2

3

3

Conjunctivae (swelling)

3

3

2

2

2

* area/degree of damage (area: 1 = ¼, 2 = ½, 3 = ¾, 4 = whole region of cornea)

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
Severe damages to the eye were observed after test substance exposure and examination at day 7 provided no evidence for any reversibility to be expected. Thus, the test substance causes severe damages to the eyes, which in terms of classification according to Regulation (EC) No 1272/2008 implies classification as Eye Dam. 1 H318.
Executive summary:

A study for eye irritation in the rabbit was conducted with the test substance. The test substance (50 mg) was instilled into the conjunctival sac of one male and one female New Zealand White rabbit. Ocular reactions were scored at 1, 24, 48 and 72 h as well as 7 days after test substance administration. The Draize system was used for scoring eventual lesions. Cornea opacity (score 4) was noted in ½ of the whole region of the cornea at all reading points after administration in 1/2 animal. With regard to the second animal, cornea opacity (score 4) was observed in ¾ of the whole region while at 24, 48 and 72 h as well as at 7 days after administration the whole region of the cornea was affected (score 3). Iritis (score 1 – 2 in animal 1 and score 2 in animal 2) was observed in both animals at every observation. Redness of the conjunctivae was noted in both animals at 1, 24, 48, 72 h and 7 days (score 1 – 3). Swelling of the conjunctivae (score 1 – 3) was also noted through the whole observation period. Thus, under the conditions of this study, the test substance causes severe damages to the eyes, which in terms of classification according to Regulation (EC) No 1272/2008 implies classification as Eye Dam. 1, H318: Causes serious eye damage.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acceptable data regarding skin irritation/ corrosion and eye irritation/ corrosion are available for the test substance.

Skin:

A study for dermal irritation in the rabbit was conducted with the test substance. Two New Zealand White rabbits received 0.5 g of the test substance to the flank for 24 h (Thyssen, 1983). After exposure duration the test substance was removed by washing with water, soap and vegetable oil. The treated skin surface was examined directly after test substance removal, at 24 and 48 h as well as at 7 days after removal. The Draize scale was used for scoring the skin reactions. Deep reddening (erythema score 4) was noted in both animals at all reading time points. Both animals exhibited severe swelling at the application site (score 4) after test substance removal which was not fully reversible up to the end of the 7-day observation period (score 3 at 24 h, score 2 at 48 h and 7 days after test substance removal in both animals). Necrotic changes of the skin in the area of treatment were observed on the first, second and seventh day of the observation period. Thus, under the conditions of this study, the test substance is corrosive to the skin which in terms of classification according to Regulation (EC) No 1272/2008 implies classification as Skin Corr. 1, H314: Causes severe skin burns and eye damage.

 

Eye:

A study for eye irritation in the rabbit was conducted with the test substance (Thyssen, 1983). The test substance (50 mg) was instilled into the conjunctival sac of one male and one female New Zealand White rabbit. Ocular reactions were scored at 1, 24, 48 and 72 h as well as 7 days after test substance administration. The Draize system was used for scoring eventual lesions. Cornea opacity (score 4) was noted in ½ of the whole region of the cornea at all reading points after administration in 1/2 animal. With regard to the second animal, cornea opacity (score 4) was observed in ¾ of the whole region while at 24, 48 and 72 h as well as at 7 days after administration the whole region of the cornea was affected (score 3). Iritis (score 1 – 2 in animal 1 and score 2 in animal 2) was observed in both animals at every observation. Redness of the conjunctivae was noted in both animals at 1, 24, 48, 72 h and 7 days (score 1 – 3). Swelling of the conjunctivae (score 1 – 3) was also noted through the whole observation period. Thus, under the conditions of this study, the test substance causes severe damages to the eyes, which in terms of classification according to Regulation (EC) No 1272/2008 implies classification as Eye Dam. 1, H318: Causes serious eye damage.

Justification for classification or non-classification

The available data on skin irritation meet the criteria for classification according to Regulation (EC) 1272/2008. The test substance is classified as Skin Corr. 1, H314: Causes severe skin burns and eye damage.

The available data on eye irritation meet the criteria for classification according to Regulation (EC) 1272/2008. The test substance is classified as Eye Dam., Category 1, H318: Causes serious eye damage.