Registration Dossier

Administrative data

Description of key information

Skin irritation

The Primary Irritation Index (PII) of CR SB08 was 0 and CR SB08 was categorized as non-irritant (OECD TG404).

 

Eye irritation

CR SB08was 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 February 16, 2016 to June 27, 2016
Reliability:
1 (reliable without restriction)
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: 2.5382 to 3.1200 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:
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

13

Female

3.1200

3.1897

14

Female

2.5382

2.6098

15

Female

2.8504

2.9203

Table 2. Individual skin reactions

Animal I.D.

Observation time (hours)

Grading (erythema / edema)

Test area

Control area

13

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

14

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

15

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

13

0

0

0

14

0

0

0

15

0

0

0

Primary Irritation Index (PII)c= 0

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

bPIS = (scores of test area) – (scores of control area).

cPII = 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 SB08 was 0 and CR SB08 was categorized as non-irritant. Therefore, CR SB08 was not met a category based on GHS criteria.
Executive summary:

This test using the procedures outlined in the SuperLab Study Plan for M62-151100069001EN which is based on the SOP for the OECD 404(SOPP-305) and OECD 404 (OECD, 2002). 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 SB08 was calculated to be 0. On the basis of the test results given above and according to Evaluation table for single dermal irritation, the response of CR SB08 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 February 16, 2016 to June 27, 2016
Reliability:
1 (reliable without restriction)
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: 2.8282-2.9954 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: #18, #19 and #20
Time point:
24/48/72 h
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal: #18, #19 and #20
Time point:
24/48/72 h
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal: #18, #19 and #20
Time point:
24/48/72 h
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal: #18, #19 and #20
Time point:
24/48/72 h
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

18

Female

2.9954

3.0392

19

Female

2.6542

2.6986

20

Female

2.8282

2.9162

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

18

1

Testb

0

0

0

1

0

0

Controlc

0

0

0

0

0

0

24 ± 1

Test

0

0

0

0

0

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

19

1

Test

0

0

0

1

0

0

Control

0

0

0

0

0

0

24 ± 1

Test

0

0

0

0

0

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

20

1

Test

0

0

0

1

0

0

Control

0

0

0

0

0

0

24 ± 1

Test

0

0

0

0

0

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

aObservation time was started after application of the test article

bLeft eye of the test rabbits

cRight eye of the test rabbits

Interpretation of results:
GHS criteria not met
Conclusions:
According to OECD 405 test method, CR SB08 showed that no irritant to the eye. Therefore, CR SB08 was not met a category based on GHS criteria.
Executive summary:

This test using the procedures outlined in the SuperLab Study Plan for M62-151100078001EN which is based on the SOP for the OECD 405 (SOPP-306) and OECD 405 (OECD, 2012). There were no test article effects on body weight.Reversiblechemosiswith score of 1 was observed within 1 hours after test article application.CR SB08 was given by a single ocular application at 0.1 g amount to NZW female rabbits and followed by ocular examination within 72 hoursand a 4 days clinical observation period. Conjunctivachemosiswith score 1 was determined within 24 hours and fully recovered. On the basis of the test results given above, the response of the test article was not any irritant to the eye.

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

Additional information

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 SB08 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 SB08 was categorized as non-irritant.

 

Eye irritation

There were no test article effects on body weight. Reversiblechemosisof conjunctivae with score of 1 was observed within 1 hours after test article application.CR SB08 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. Conjunctivachemosiswith score 1 was determined within 24 hours and fully recovered.On the basis of the test results given above, the response of the test article was not any irritant to the eye.

Justification for classification or non-classification