Registration Dossier

Administrative data

Description of key information

Skin irritation / corrosion: corrosive (rabbit);

Eye irritation: corrosive (rabbit)

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:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well documented report which meets basic scientific principles.
Principles of method if other than guideline:
BASF test: Two animals were treated for 1, 5 or 15 min using occlusive conditions. An application site of 2.5x2.5 cm was covered with the liquid test substance. The animals were observed for 8 days and skin changes were recorded daily. For a final evaluation, the findings from 24 and 48 hours from the raw data were taken into account.
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 3.0 and 3.1 kg
Type of coverage:
occlusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated skin of the same animal served as control
Amount / concentration applied:
pure
Duration of treatment / exposure:
1, 5 and 15 min
Observation period:
8 days
Number of animals:
2
Details on study design:
TEST SITE
- Area of exposure: 2.5x2.5 cm

REMOVAL OF TEST SUBSTANCE
- Washing (if done): conc. Lutrol and 50 % Lutrol solution
- Time after start of exposure: 1, 5 or 15 min post exposure
Irritation parameter:
other: Necrosis-score
Basis:
mean
Remarks:
1, 5 and 15 min exposure
Time point:
24 h
Score:
3
Max. score:
3
Reversibility:
not reversible
Irritation parameter:
other: Necrosis-score
Basis:
mean
Remarks:
1, 5 and 15 min exposure
Time point:
other: 8 d
Score:
3
Max. score:
3
Reversibility:
not reversible
Irritant / corrosive response data:
Slight erythema (grade 2), slight edema (grade 1), partly extended beyond the area of exposure were observed in all animals on the day of application. After a 1 min exposure necrosis (grade 3) was observed. A 5 min or 15 min exposure led to leathery-like full thickness necrosis (grade 3).
Interpretation of results:
Category 1A (corrosive) based on GHS criteria
Conclusions:
The test substance caused severe necrosis after an 1-min exposure. The first scoring was made 24 h after the application of the test substance. As it cannot be excluded that the corrosive effects already occurred during an observation period ≤ 1 h, the test substance is assigned to category 1A .
Executive summary:

In a primary skin irritation study (BASF test), the undiluted test substance was applied to the back of two Vienna White rabbits for 1, 5 or 15 min using occlusive conditions. An application site of 2.5 x 2.5 cm was covered with the liquid test substance. The animals were observed for 8 days and skin changes were recorded daily.

After a 1-min exposure necrosis (grade 3) was observed. A 5-min or 15-min exposure led to leathery-like full thickness necrosis (grade 3). Additionally, slight erythema (grade 2) and slight edema (grade 1), partly extending beyond the area of exposure were observed in all animals on the day of application.

Endpoint:
skin irritation: in vivo
Type of information:
not specified
Adequacy of study:
other information
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Secondary literature.
Principles of method if other than guideline:
Method: no data
GLP compliance:
not specified
Species:
rabbit
Strain:
not specified
Type of coverage:
open
Preparation of test site:
not specified
Vehicle:
not specified
Controls:
not specified
Amount / concentration applied:
Concentration: 5 mg
Duration of treatment / exposure:
24 hour(s)
Observation period:
no data
Number of animals:
no data

Severe (not further specified).

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable publication but only limited data is given.
Principles of method if other than guideline:
see details in remarks on material and methods
GLP compliance:
no
Species:
rabbit
Strain:
not specified
Type of coverage:
not specified
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.01 ml
Duration of treatment / exposure:
24 hour(s)
Observation period:
no data
Number of animals:
5
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24 h
Score:
6
Max. score:
10
Reversibility:
not reversible

The severity of the reaction was graded 6 by the authors, indicating necrosis when test substance was applied undiluted.

Interpretation of results:
Category 1 (corrosive) based on GHS criteria
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Referenceopen allclose all

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:
other: Acceptable, well documented report which meets basic scientific principles.
Principles of method if other than guideline:
BASF test:
50 µl of the test substance were applied to the conjunctival sac of one eye in 2 animals. The animals were observed after 10 min, 1 and 3 h on the day of treatment and up to 8 days afterwards. Findings were recorded daily. The eyes were not washed out after 24 hours as specified in OECD Guideline 405.
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.74 and 2.89 kg
Vehicle:
unchanged (no vehicle)
Controls:
other: The adjacent eye served as saline control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 50 µl
Observation period (in vivo):
8 days
Number of animals or in vitro replicates:
2
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 1 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 8 d
Score:
4
Max. score:
4
Reversibility:
not reversible

The application of the test substance caused corrosion to the exposed eyes predominantly expressed by severe corneal opacity and chemosis.

Severe corneal opacity is considered to be an irreversible effect to ophthalmic tissue. At the end of the observation period after 8 days beginning staphyloma, corneal opacity, partially necrotic lid margins and suppuration was noted.

The original gradings were converted into the numerical grading according to the OECD Draize system.

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
Under the conditions of this study the test substance caused severe damage to the rabbit eye.
Executive summary:

In an eye irritation study (internal test method) in rabbits, 50 µL of the undiluted test substance were applied to the conjunctival sac of one eye in 2 rabbits. The animals were observed after 10 min, 1 and 3 h on the day of treatment and up to 8 days afterwards. Findings were recorded daily. The eyes were not washed out after 24 hours.

The application of the test substance caused corrosion to the exposed eyes predominantly expressed by severe corneal opacity and chemosis.

At the end of the observation period after 8 days beginning staphyloma, corneal opacity, partially necrotic lid margins and suppuration were noted.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable publication but only limited data is given.
Principles of method if other than guideline:
see details in remarks on material and methods
GLP compliance:
no
Species:
rabbit
Strain:
not specified
Vehicle:
other: either undiluted or diluted in water or propylene glycol
Controls:
not specified
Duration of treatment / exposure:
24 h
Observation period (in vivo):
24 h
Number of animals or in vitro replicates:
5
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24 h
Score:
8
Max. score:
10
Reversibility:
not reversible

The reaction was graded 8 on a scale of 10, with the value 1 indicating at most a very small area of necrosis due to 0.5 ml of undiluted chemical, grade 5 indicates a so-called severe burn from 0.005ml, and the value 10 indicates a severe burn from 0.5 ml of a 1% solution in either water or propylene glycol.

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation / corrosion:

In a primary skin irritation study (BASF 1966), the undiluted test substance was applied to the back of two Vienna White rabbits for 1, 5 or 15 min under occlusive conditions. An application site of 2.5 x 2.5 cm was covered with the liquid test substance. The animals were observed for 8 days and skin changes were recorded daily.

After a 1 min exposure necrosis (grade 3) was observed. A 5 min or 15 min exposure led to leathery-like full thickness necrosis (grade 3). Additionally, slight erythema (grade 2) and slight edema (grade 1), partly extending beyond the area of exposure were observed in all animals on the day of application.

Corrosive effects to skin were also found in two other studies where only limited data is provided.

Additionally, internal reports of accidental poisonings showed signs of skin irritation to varying degrees, supporting the local damaging properties of the test substance (see IUCLID section 7.10.3)

 

Eye irritation:

In an eye irritation study (internal test method) in rabbits, 50 µL of the undiluted test substance were applied to the conjunctival sac of one eye in 2 rabbits. The animals were observed after 10 min, 1 and 3 h on the day of treatment and up to 8 days afterwards. Findings were recorded daily. The eyes were not washed out after 24 hours.

The application of the test substance caused corrosion to the exposed eyes predominantly expressed by severe corneal opacity and chemosis.

At the end of the observation period after 8 days beginning staphyloma, corneal opacity, partially necrotic lid margins and suppuration was noted.

A further studies with only limited data provided, confirmed these severe corrosive effects.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance has to be classified as corrosive to the skin (cat. 1A) and severly eye damaging (cat. 1) under Regulation (EC) No. 1272/2008, as amended for the 13th time in Regulation (EU) 2018/1480.