Registration Dossier

Administrative data

Description of key information

Skin irritation

CJ305was not irritant to the skin (OECD TG439).

 

Eye irritation       

CJ305 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 vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From November 29, 2016 to June 09, 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
GLP compliance:
yes
Test system:
human skin model
Remarks:
EPISKIN Small Model
Source species:
human
Cell type:
other: reconstructed epidermis of normal human keratinocytes
Cell source:
other: Adult donors
Control samples:
yes, concurrent negative control
yes, concurrent positive control
Irritation / corrosion parameter:
other: % mean cell viability
Value:
100.2
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
no indication of irritation

Table 1. Optical Density (OD) and the calculated Non Specific Colour % (NSCliving%) of the Additional Control Tissues

Additional control

Optical Density (OD)

NSC %

 

Measured

Blank corrected

Treated with CJ305

1

0.048

0.002

1.0

2

0.059

0.013

mean

0.007

Notes:

1. Mean blank value was 0.046.

2. Optical density means the mean value of the duplicated wells for each sample (rounded to three decimal places).

3. NSC %:Non Specific Colour %

Table 2. Optical Density (OD) and the calculated relative viability % of the samples

Substance

Optical Density (OD)

Viability

(% RV)

SD

 

Measured

Blank corrected

Negative Control:

Phosphate buffered saline

1

0.826

0.780

107.1

6.1

2

0.746

0.699

96.0

3

0.752

0.706

96.9

mean

0.728

100.0

Positive Control:

5% (w/v) SDS solution

1

0.101

0.055

7.5

1.5

2

0.106

0.060

8.2

3

0.085

0.039

5.3

mean

0.051

7.0

Test Item:

CJ305

1

0.766

0.720

98.8

1.6

2

0.789

0.742

101.9

3

0.773

0.726

99.7

mean

0.729

100.2

Notes:

1. Mean blank value was 0.046.

2. Optical density means the mean value of the duplicated wells for each sample (rounded to three decimal places).
Interpretation of results:
GHS criteria not met
Conclusions:
According to OECD 439 test method, CJ305 was non-irritant to skin. CJ305 was not met classification on GHS criteria.
Executive summary:

This test using the procedures outlined in the CiToxLAB Study Plan for 16/377-043B and OECD 439 (OECD, 2015). An in vitro skin irritation test of CJ305 was performed in a reconstructed human epidermis model. EPISKINTM(SM) is designed to predict and classify the irritation potential of chemicals by measuring its cytotoxic effect as reflected in the MTT assay. All data met the validity criteria. The mean cell viability of CJ305 was 100.2% compared to the negative control. This is above the threshold of 50%. Therefore, CJ305 was considered as being non-irritant to skin.

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 December 23, 2016 to April 13, 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 2-3 months
- Weight at study initiation: 2189-2410 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 and 72 hours, 7 and 14 days
Number of animals or in vitro replicates:
Three
Irritation parameter:
cornea opacity score
Basis:
animal: #01
Time point:
24/48/72 h
Score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal: #02
Time point:
24/48/72 h
Score:
0.66
Reversibility:
fully reversible within: 72hours
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal: #03
Time point:
24/48/72 h
Score:
0.33
Reversibility:
fully reversible within: 48 hours
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
animal: #01, 02 and 03
Time point:
24/48 h
Score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal: #01
Time point:
24/48/72 h
Score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal: #02
Time point:
24/48/72 h
Score:
0.33
Reversibility:
fully reversible within: 48hours
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal: #03
Time point:
24/48/72 h
Score:
1
Reversibility:
fully reversible within: Day 7
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal: #01
Time point:
24/48/72 h
Score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal: #02 and 03
Time point:
24/48/72 h
Score:
0.33
Reversibility:
fully reversible within: 48hours
Remarks on result:
positive 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

01

2189

2262

73

Normal1

02

2410

2483

73

Normal1

03

2327

2406

79

Normal2

1: D1-D7

2: D1-D14

 

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

Animal I.D.

Observation point

Cornea (D/A5)1

Iris

Conjunctivae (R/D)2

01

1 h4

0/-

0

2/1

24 h

0/-

03

0/0

48 h

0/-

03

0/0

72 h

0/-

03

0/0

D7

-

Normal

-

02

1 h

0/-

0

2/1

24 h

1/1

03

1/1

48 h

1/1

03

0/0

72 h

0/-

03

0/0

D7

-

Normal

-

03

1 h

0/-

0

2/1

24 h

1/1

03

1/1

48 h

0/-

03

1/0

72 h

0/-

03

1/0

D7

0/-

03

0/0

D14

-

Normal

-

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

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

3Red colored iris

4Eye rinsed with saline at this time point

5Area of corneal opacity involved: 1=less than one-quarter; 2=greater than one-quarter but less than half; 3=greater than half but less than three-quarter; 4=greater than three-quarter, up to whole area

-: Not available

Interpretation of results:
GHS criteria not met
Conclusions:
According to OECD 405 test method, CJ305 showed that positive irritant to the eye. Therefore, CJ305 was not met a category based on GHS criteria.
Executive summary:

This test using the procedures outlined in the QPS Taiwan Study Plan for T65316004-IR which is based on the SOP for the OECD 405 (CTPS-TE00441) and OECD 405 (OECD, 2012). CJ305 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 iris. Reversible corneal opacity, conjunctiva redness and chemosis were observed within 7 days. On the basis of the test results given above, CJ305 showed the light irritation to eyes. However, the result has not met a category based on GHS criteria.

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

Additional information

Skin irritation

An in vitro skin irritation test of CJ305 was performed in a reconstructed human epidermis model. EPISKINTM(SM) is designed to predict and classify the irritation potential of chemicals by measuring its cytotoxic effect as reflected in the MTT assay. All data met the validity criteria. The mean cell viability of CJ305 was 100.2% compared to the negative control. This is above the threshold of 50%. Therefore, CJ305 was considered as being non-irritant to skin.

 

Eye irritation

CJ305 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 iris. Reversible corneal opacity, conjunctiva redness and chemosis were observed within 7 days. On the basis of the test results given above, CJ305 showed the light irritation to eyes. However, the result has not met a category based on GHS criteria.

Justification for classification or non-classification