Registration Dossier

Administrative data

Description of key information

Skin irritation

CR SB32N2 was not irritant to the skin (OECD TG404).

 

Eye irritation       

CR SB32N2 was not 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 06, 2017 to May 18, 2017
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: the animal health research institute, council of agriculture, executive yuan
- Age at study initiation: approximately 4 to 5 months
- Weight at study initiation: 2924 to 3276 g
- Housing: individually in a stainless steel wire mesh cage
- Water: ad libitum
- Acclimation period: at least 5 days
- Temperature (°C): 21 ± 2 °C
- Humidity (%): 50 ± 20%
- Photoperiod: 12hrs dark / 12hrs light
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
water
Remarks:
Water for injection (WFI)
Controls:
yes, concurrent vehicle
Amount / concentration applied:
- Amount(s) applied (volume or weight with unit): 0.5 g test article was moistened with 0.4 mL water for injection
Duration of treatment / exposure:
4-4.5 hours
Observation period:
1, 24, 48 and 72 hours
Number of animals:
three
Details on study design:
- Area of exposure: left dorsal area
- Washing (if done): with lukewarm 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)
Time point:
24/48/72 h
Score:
0
Remarks on result:
no indication of irritation

Table 1. Individual Body Weights and Clinical Observations

Animal ID

Body weight (g)

Body weight change (g)

Clinical observation

D1

D4

D4-D1

1

2956

2955

-1

Normal

2

2924

3057

133

Normal

3

3276

3354

78

Normal

Table 2. Individual Scores and Total Scores for Skin Irritation During 72 hours

Animal ID

Observation point

Erythema

Edema

Control Site

1

1 h

0

0

24 h

0

0

48 h

0

0

72 h

0

0

2

1 h

0

0

24 h

0

0

48 h

0

0

72 h

0

0

3

1 h

0

0

24 h

0

0

48 h

0

0

72 h

0

0

Test Site

1

1 h

0

0

24 h

0

0

48 h

0

0

72 h

0

0

2

1 h

0

0

24 h

0

0

48 h

0

0

72 h

0

0

3

1 h

0

0

24 h

0

0

48 h

0

0

72 h

0

0

Total irritation score = 0

PII = 0

Total irritation score = The sum of irritation score got from test site at 24, 48 and 72h minus the sum of irritation score got from control site at the same time points.

Interpretation of results:
GHS criteria not met
Conclusions:
According to OECD 404 test method and Draize Dermal Classification System, the PII for CR SB32N2 in intact skin was 0 and CR SB32N2 was categorized as non-irritant. CR SB32N2 was not met classification on GHS criteria.
Executive summary:

This test using the procedures outlined in the QPS Taiwan Study Plan for T65316009-IR which is based on the SOP for the OECD 404 (CTPS-TE00440) 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. Neither erythema nor edema was observed within 72 hours. The Primary Irritation Index for CR SB32N2 was calculated to be 0. On the basis of the test results given above and according to Draize Dermal Classification System, the response of CR SB32N2 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 06, 2017 to May 18, 2017
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: the animal health research institute, council of agriculture, executive yuan
- Age: approximately 4-5 months
- Weight at study initiation: 2812-3208 g
- Housing: individually in a stainless steel wire mesh cage
- Water: ad libitum
- Acclimation period: at least 5 days
- Temperature (°C): 21 ± 2 °C
- Humidity (%): 50 ± 20%
- 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
Observation period (in vivo):
1, 24, 48, 72 hours and 7, 14 day
Number of animals or in vitro replicates:
Three
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal: #1 and #3
Time point:
24/48/72 h
Score:
0.66
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal: #2 and #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 24 hours
Remarks on result:
no indication of irritation

Table 1. Individual Body Weights and Clinical Observations

Animal ID

Body weight (g)

Body weight change (g)

(D4-D1)

Clinical observation

D1

D4

4

2812

2840

28

Normal1

5

3169

3130

-39

Normal2

6

3208

3247

39

Normal2

1: D1-D14

2: D1-D7

 

Table 2. Eye Irritation Scores at Observation Point on Treated Eye

Animal I.D.

Observation point

Cornea (D/A)1

Iris

Conjunctivae (R/D)2

4

1 h

0/-

03

1/1

24 h

0/-

03

1/1

48 h

0/-

03

1/0

72 h

0/-

03

0/0

Day 7

-

03

-

Day 14

-

Normal

-

5

1 h

0/-

03

1/1

24 h

0/-

03

1/0

48 h

0/-

03

0/0

72 h

0/-

03

0/0

Day 7

-

Normal

-

6

1 h

0/-

03

1/1

24 h

0/-

03

1/0

48 h

0/-

03

1/0

72 h

0/-

03

0/0

Day 7

-

Normal

-

1(D/A) = (Degree of density/Area of opacity)                                                                

2(R/D) = (Redness/Chemosis)

3Iris stained, deep pink

-: Not available

Interpretation of results:
GHS criteria not met
Conclusions:
According to OECD 405 test method, CR SB32N2 showed that was not positive irritant to the eye. Therefore, CR SB32N2 was not met a category based on GHS criteria.
Executive summary:

This test using the procedures outlined in the QPS Taiwan Study Plan for T65316008-IR which is based on the SOP for the OECD 405 (CTPS-TE00441) and OECD 405 (OECD, 2012). CR SB32N2 was given by a single ocular application at 0.1 g amount to NZW female rabbits and followed by ocular examination and clinical observation no more than 14 days. There were no test article effects on body weight. No irritation reaction in cornea and iris. Reversible conjunctiva redness and chemosis were 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 judged as a positive 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

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. Neither erythema nor edema was observed within 72 hours. The Primary Irritation Index forCR SB32N2was calculated to be 0. On the basis of the test results given above and according to Draize Dermal Classification System, the response of CR SB32N2 was categorized as non-irritant.

 

Eye irritation

CR SB32N2 was given by a single ocular application at 0.1 g amount to NZW female rabbits and followed by ocular examination and clinical observation no more than 14 days. There were no test article effects on body weight. No irritation reaction in cornea and iris. Reversible conjunctiva redness and chemosis were 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 judged as a positive irritant to the eye.

Justification for classification or non-classification