Registration Dossier

Administrative data

Description of key information

Skin irritation

The Primary Irritation Index (PII) of CR SB87 was 0 and CR SB87 was categorized as non-irritant (OECD TG404).

 

Eye irritation

CR SB87was not any irritant to the eye (OECD TG405).

 

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 April 11, 2016 to October 13, 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
- Source: WEI XIN HANG
- Weight at study initiation: 2.7354 to 2.8912 kg
- Housing: individually in a stainless steel wire mesh cage
- Water: ad libitum
- Acclimation period: 7 days
- Temperature (°C): 21 ± 2 °C
- Humidity (%): 55 ± 15%
- Photoperiod: 12hrs dark / 12hrs light
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
physiological saline
Controls:
yes, concurrent vehicle
Amount / concentration applied:
- Amount(s) applied (volume or weight with unit): 0.5 g test article was moistened with 0.5 mL normal saline
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48 and 72 hours
Number of animals:
Three
Details on study design:
- Area of exposure: upper left and lower right dorsal area
- Washing (if done): with distilled water
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation

Table 1. Body weight of the rabbits

Animal ID

Sex

Body weight (kg)

Day 1

Day 4

40

Female

2.8912

2.9300

46

Female

2.7354

2.7776

47

Female

2.8201

2.8605

Table 2. Individual skin reactions

Animal I.D.

Observation time (hours)

Grading (erythema / edema)

Test area

Control area

40

1

0/0

0/0

0/0

0/0

24 ± 1

0/0

0/0

0/0

0/0

48 ± 1

0/0

0/0

0/0

0/0

72 ± 1

0/0

0/0

0/0

0/0

46

1

0/0

0/0

0/0

0/0

24 ± 1

0/0

0/0

0/0

0/0

48 ± 1

0/0

0/0

0/0

0/0

72 ± 1

0/0

0/0

0/0

0/0

47

1

0/0

0/0

0/0

0/0

24 ± 1

0/0

0/0

0/0

0/0

48 ± 1

0/0

0/0

0/0

0/0

72 ± 1

0/0

0/0

0/0

0/0

Table 3. Individual animal primary irritation scores

Animal I.D.

Scoresa

Primary Irritation Scores (PIS)b

Test area

Control area

40

0

0

0

46

0

0

0

47

0

0

0

Primary Irritation Index (PII)c= 0

a Sum of scores at all time intervals on backside skin in each rabbit and divided the sum by the total number of observation.

b PIS = (scores of test area) – (scores of control area).

c PII = Sum of PIS÷number of animals.

Interpretation of results:
GHS criteria not met
Conclusions:
According to OECD 404 test method and Evaluation table for single dermal irritation, the PII for CR SB87 was 0 and CR SB87 was categorized as non-irritant. Therefore, CR SB87 was not met a category based on GHS criteria.
Executive summary:

This test using the procedures outlined in the SuperLab Study Plan for M62-151100117001EN which is based on the SOP for the OECD 404 (SOPP-305) and OECD 404 (OECD, 2015). The sites were grades for erythema and edema at 1, 24, 48 and 72 hours after the patches removal. No clinical signs of toxicity were found. Body weight changes were within the normal range in all animals. All animals was no formation of erythema, eschar or edema on the test area within 72 hours after patch removal. The Primary Irritation Index for CR SB87 was calculated to be 0. On the basis of the test results given above and according toEvaluation table for single dermal irritation, the response of CR SB87 was categorized as non-irritant.

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:
From April 11, 2016 to October 15, 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
- Source: WEI XIN HANG
- Weight at study initiation: 2.1086-2.3962 kg
- Housing: individually in a stainless steel wire mesh cage
- Water: ad libitum
- Acclimation period: 7 days
- Temperature (°C): 21 ± 2 °C
- Humidity (%): 55 ± 15%
- Photoperiod: 12-hrs dark / 12-hrs light
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
- Amount(s) applied (volume or weight with unit): 0.1 g
Duration of treatment / exposure:
1 hours
Observation period (in vivo):
1, 24, 48 and 72 hours
Number of animals or in vitro replicates:
Three
Irritation parameter:
cornea opacity score
Basis:
animal: #43, #45 and #48
Time point:
24/48/72 h
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal: #43, #45 and #48
Time point:
24/48/72 h
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal: #43, #45 and #48
Time point:
24/48/72 h
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal: #43, #45 and #48
Time point:
24/48/72 h
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Remarks on result:
probability of weak irritation

Table 1. Body weight of the rabbits

Animal ID

Sex

Body weight (kg)

Day 1

Day 4

43

Female

2.2104

2.2492

45

Female

2.1086

2.1508

48

Female

2.3962

2.4366

Table 2. Individual response of the test rabbits

Animal I.D.

Timea (hour)

 

Grades of the irritation reaction

Cornea

Conjunctivae

Iris

Opacity

Area

Redness

Chemosis

Discharge

43

1

Testb

0

0

0

3

2

0

Controlc

0

0

0

0

0

0

24 ± 1

Test

0

0

0

2

1

0

Control

0

0

0

0

0

0

48 ± 1

Test

0

0

0

1

0

0

Control

0

0

0

0

0

0

72 ± 1

Test

0

0

0

0

0

0

Control

0

0

0

0

0

0

45

1

Test

0

0

0

1

2

0

Control

0

0

0

0

0

0

24 ± 1

Test

0

0

0

1

1

0

Control

0

0

0

0

0

0

48 ± 1

Test

0

0

0

0

0

0

Control

0

0

0

0

0

0

72 ± 1

Test

0

0

0

0

0

0

Control

0

0

0

0

0

0

48

1

Test

0

0

0

1

2

0

Control

0

0

0

0

0

0

24 ± 1

Test

0

0

0

1

1

0

Control

0

0

0

0

0

0

48 ± 1

Test

0

0

0

0

0

0

Control

0

0

0

0

0

0

72 ± 1

Test

0

0

0

0

0

0

Control

0

0

0

0

0

0

a Observation time was started after application of the test article                                  

b Left eye of the test rabbits

c Right eye of the test rabbits

Interpretation of results:
GHS criteria not met
Conclusions:
According to OECD 405 test method, CR SB87 showed that weak irritant to the eye. Therefore, CR SB87 was not met a category based on GHS criteria.
Executive summary:

This test using the procedures outlined in the SuperLab Study Plan for M62-151100126001EN which is based on the SOP for the OECD 405 (SOPP-306) and OECD 405 (OECD, 2012). CR SB87 was given by a single ocular application at 0.1 g amount to NZW female rabbits and followed by ocular examination within 72 hours and a 4 days clinical observation period. There were no test article effects on body weight. Reversible conjunctival chemosis and discharge was observed within 72 hours after test article application. On the basis of the test results given above, the response of the test article was weak irritant to the eye.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Skin irritation

The sites were grades for erythema and edema at 1, 24, 48 and 72 hours after the patches removal.No clinical signs of toxicity were found. Body weight changes were within the normal range in all animals. All animals was no formation of erythema, eschar or edema on the test area within 72 hours after patch removal. The Primary Irritation Index for CR SB87 was calculated to be 0. On the basis of the test results given above and according toEvaluation table for single dermal irritation, the response of CR SB87 was categorized as non-irritant.

 

Eye irritation

CR SB87 was given by a single ocular application at 0.1 g amount toNZW female rabbits and followed by ocular examination within 72 hours and a 4 days clinical observation period. There were no test article effects on body weight. Reversible conjunctivalchemosisanddischargewas observed within 72 hours after test article application.On the basis of the test results given above, the response of the test article was not any irritant to the eye.