Registration Dossier

Administrative data

Description of key information

Skin: not irritating (rabbit, 1975, occlusive application for 1 min, 5 min, 15 min and 20 h)

Eyes: not irritating (rabbit, 1974, comparable to OECD TG 405)

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:
limited documentation, only 2 animals used, 72-hrs reading missing, observation period only 8 days
Principles of method if other than guideline:
Two animals were treated for 1, 5, 15 min or 20 h 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. 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 or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 3.11 and 3.57 kg
Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): ca. 0.5 mL

Duration of treatment / exposure:
1min, 5 min, 15 min and 20 h, respectively
Observation period:
8 days
Number of animals:
2
Details on study design:
TEST SITE
- Area of exposure: 2.5*2.5 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:
erythema score
Remarks:
1 min exposure
Basis:
animal #1
Time point:
other: 24 h - 48 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Remarks on result:
other: Erythema extending beyond the area of application; scaling at study termination.
Irritation parameter:
erythema score
Remarks:
1 min exposure
Basis:
animal #2
Time point:
other: 24 h - 48 h
Score:
1.5
Max. score:
4
Reversibility:
fully reversible within: 8 days
Remarks on result:
other: Erythema extending beyond the area of application; scaling at study termination.
Irritation parameter:
erythema score
Remarks:
5 min exposure
Basis:
animal #1
Time point:
other: 24 h - 48 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Remarks on result:
other: Erythema extending beyond the area of application; scaling at study termination.
Irritation parameter:
erythema score
Remarks:
5 min exposure
Basis:
animal #2
Time point:
other: 2 h - 48 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 8 days
Remarks on result:
other: Erythema extending beyond the area of application; scaling at study termination.
Irritation parameter:
erythema score
Remarks:
15 min exposure
Basis:
animal #1
Time point:
other: 24 h - 48 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Remarks on result:
other: Erythema extending beyond the area of application; scaling at study termination.
Irritation parameter:
erythema score
Remarks:
15 min exposure
Basis:
animal #2
Time point:
other: 24 h - 48 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 8 days
Remarks on result:
other: Erythema extending beyond the area of application; scaling at study termination.
Irritation parameter:
edema score
Remarks:
1, 5 and 15 min exposure
Basis:
mean
Remarks:
out of both animals
Time point:
other: 24 h - 48 h
Score:
0
Max. score:
4
Reversibility:
other: no symptoms
Irritation parameter:
erythema score
Remarks:
20 h exposure
Basis:
animal #1
Time point:
other: 24 h - 48 h
Score:
2.5
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Remarks on result:
other: Erythema extending beyond the area of application; scaling extending beyond the area of application at study termination.
Irritation parameter:
erythema score
Remarks:
20 h exposure
Basis:
animal #2
Time point:
other: 24 h - 48 h
Score:
2.5
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Remarks on result:
other: Erythema extending beyond the area of application; scaling extending beyond the area of application at study termination.
Irritation parameter:
edema score
Remarks:
20 h exposure
Basis:
animal #1
Time point:
other: 24 h - 48 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 5 days
Irritation parameter:
edema score
Remarks:
20 h exposure
Basis:
animal #2
Time point:
other: 24 h - 48 h
Score:
0
Max. score:
4
Reversibility:
other: no symptons

Table 1: Mean erythema score after 24 and 48 h (72 h reading is missing)

Exposure time 24 h 48 h 72 h mean
animal 1 animal 2 animal 1 animal 2 animal 1 animal 2 animal 1 animal 2
1 min 2 1 2 2 - - 2 1.5
5 min 2 1 2 1 - - 2 1
15 min 2 1 2 1 - - 2 1
20 h 2 2 3 3 - - 2.5 2.5

Table 2: Mean edema score after 24 and 48h (72 h reading is missing)

Exposure time 24 h 48 h 72 h mean
animal 1 animal 2 animal 1 animal 2 animal 1 animal 2 animal 1 animal 2
1 min 0 0 0 0 - - 0 0
5 min 0 0 0 0 - - 0 0
15 min 0 0 0 0 - - 0 0
20 h 0 0 2 0 - - 1 0

The original BASF grading was converted into the numerical grading according the OECD Draize system.

Interpretation of results:
GHS criteria not met
Conclusions:
After exposure times of 1, 5, 15 min and 20 h the test material caused slight to moderate reddening of the dorsal rabbit skin extending beyond the area of exposure. After 20 h of exposure 1 animal showed slight edema after 48 h. At the end of the observation period of 8 days the animals showed at all exposure times scale formation which was extending beyond the area of exposure in the 20 h application. According to the criteria laid down in the Regulation (EC) No. 1272/2008, the substance does not need to be classified and labeled as skin irritating.
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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
study protocol is in principle similar to OECD TG 405, with acceptable restrictions (only 50 µL instilled, only 2 animals used, observation period only 8 days)
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
Only 50 µL instilled, only 2 animals used, observation period only 8 days.
Principles of method if other than guideline:
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. The report describes findings after 1 and 24 hours and at the end of the observation period. For final evaluation, the findings after 48 and 72 hours from the raw data were taken into account.
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 3.06 and 3.19 kg
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent negative control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 50 µL
Duration of treatment / exposure:
single application
Observation period (in vivo):
8 days
Number of animals or in vitro replicates:
2
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24 h - 48 h - 72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 8 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24 h - 48 h - 72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 8 days
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24 h - 48 h - 72 h
Score:
0
Max. score:
4
Reversibility:
other: no symptoms
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24 h - 48 h - 72 h
Score:
0
Max. score:
2
Reversibility:
other: no symptoms
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24 h - 48 h - 72 h
Score:
0
Max. score:
4
Reversibility:
other: no symptoms

Table 1: Eye irritation parameter observed in two treated animals

Exposure time Opacity Iritis Erythema Chemosis
animal 1 animal 2 animal 1 animal 2 animal 1 animal 2 animal 1 animal 2
1 h 0 0 0 0 1 1 0 0
24 h 0 0 0 0 1 1 0 0
48 h 0 0 0 0 1 1 0 0
72 h 0 0 0 0 1 1 0 0
8 d 0 0 0 0 0 0 0 0
Mean value over 24/48/72 h 0 0 0 0 1 1 0 0

The original BASF grading was converted into the numerical grading according to the OECD Draize system.

Interpretation of results:
GHS criteria not met
Conclusions:
After exposure times of 25, 48 and 72 h the application of the test material caused slight reversible erythema to the eyes of the exposed animals.
At the end of the observation period of 8 days all effects were reversible.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

In a study according to an internal protocol undiluted test substance was applied under occlusive conditions to the skin of rabbits for one minute, 5 minutes, 15 minutes and 20 hours, respectively. Occlusive exposure caused slight to moderate reddening of the dorsal rabbit skin extending beyond the area of exposure. Mean erythema scores (24-48 h) were 1.75 (1 min), 1.5 (5 min), 1.5 (15 min) and 2.5 (20 h). Mean edema scores (24-48 h) were 0 (1 min), 0 (5 min), 0 (15 min) and 0.5 (20 h). Since the readings after 72 h were missing from the raw data, only readings after 24 and 48 h were taken into consideration for scoring.

At the end of the observation period of 8 days erythema and edema had fully reversed. The animals showed scale formation at all exposure times. In case of the 20 h application scaling was extending beyond the area of exposure.

Since application for 20h under occlusive dressing gives overpredictive results as compared to the specifications of the OECD TG 404, only the effects after 1, 5, and 15 min application were considered for estimating the skin irritation potential of the substance. Taking all the relevant data into account, the test substance is not considered irritating to rabbit skin.

 

 

Eye irritation:

In a study comparable to OECD TG 405 undiluted test substance was instilled into one eye of two rabbits. The adjacent eyes were treated with saline and served as control. The eyes were not washed out after 24 hours as specified in OECD Guideline 405. Mean scores for cornea, iris, conjunctivae and chemosis (24-48-72 hours) were 0, 0, 1, and 0, respectively. All effects were fully reversible within 8 days.

Thus, the substance is not irritating to the eyes of rabbits.

 

 

Respiratory irritation:

No respiratory irritation was reported in the studies performed. There is some evidence from the described inhalation hazard test that the test material vapours may be slightly irritating to the mucous membranes of rats (1975; reliability 2). However, the observations do not indicate respiratory irritation.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008, as amended for the thirteenth time in Regulation (EU) No 2018/1480. As a result the substance is not considered to be classified for irritation under Regulation (EC) No. 1272/2008.