2-[{6-[(4-amino-6-chloro-1,3,5-triazin-2-yl)(methyl)amino]-1-hydroxy-3-sulfonaphthalen-2-yl}diazenyl]naphthalene-1,5-disulfonic acid, lithium sodium salts

Endpoint summary

Description of key information

Skin irritation

CJ302 is not classified as skin irriatant (OECD TG404).

 

Eye irritation

CJ 302 was not judged as a positive 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 Decenber 29, 2015 to February 18, 2016 Single exposure, 72 hours observation (reversible changes)

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

- Source: Kitayama Labes Co., Ltd. (Japan)
- Age at study initiation: approximately 5 to 6 months
- Weight at study initiation: 2891 to 3910 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

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 0.3 mL water for injection

Duration of treatment / exposure:

4-4.5 hours

Observation period:

1, 24, 48, 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:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

1

Remarks on result:

probability of weak irritation

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #3

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)

Score:

0.22

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of mild 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	2891	2931	40	Normal
2	3910	3929	19	Normal
3	3031	3049	18	Normal

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

Animal ID	1				2				3
	Score on each observation point (hour)
	1	24	48	72	1	24	48	72	1	24	48	72
Control site
Erythema	0	0	0	0	0	0	0	0	0	0	0	0
Edema	0	0	0	0	0	0	0	0	0	0	0	0
Total irritation score for vehicle*	0				0				0
Test site
Erythema	1	1	1	0	0	0	0	0	0	0	0	0
Edema	0	0	0	0	0	0	0	0	0	0	0	0
Total irritation score for vehicle*	2				0				0
PII**	0.22

* The sum of scores at 24, 48 and 72 hours.

** (Total irritation score for test article-Total irritation score for vehicle)/9

Interpretation of results:

GHS criteria not met

Conclusions:

According to OECD 404 test method and Draize Dermal Classification System, the result does not meet the CLP criteria. Therefore, CJ302 is not classified.

Executive summary:

This test using the procedures outlined in the QPS Taiwan Study Plan for T65315014-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. Erythema with score 1 was observed in one animal during 48 hours after patch removal. The Primary Irritation Index for CJ302 was calculated to be 0.22. On the basis of the test results given above and according to Draize Dermal Classification System, the response of CJ302 was not classified.

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 15, 2016 to June 1, 2016. single exposure, 96 hours observation period (revsersible)

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

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 at study initiation: 4-5 months
- Weight at study initiation: 3274-3503 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): 100 mg

Duration of treatment / exposure:

1 hour

Observation period (in vivo):

1, 24, 48 and 72 hours

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:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 48hr

Remarks on result:

probability of weak 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	3491	3511	20	Normal
2	3274	3397	123	Normal
3	3503	3552	49	Normal

Table 2. Eye Irritation Scores at Observation Point (hours) on Treated Eye

Animal ID	1				2				3
	Score on each observation point (hour)
	1	24	48	72	1	24	48	72	1	24	48	72
Cornea
Degree of density	0	0	0	0	0	0	0	0	0	0	0	0
Iris	0	0	0	0	0	0	0	0	0	0	0	0
Conjunctiva
Redness	1	0	0	0	1	0	0	0	1	0	0	0
Chemosis	1	1	0	0	0	1	0	0	1	0	0	0

Interpretation of results:

GHS criteria not met

Conclusions:

According to OECD 405 test method, CJ302 showed that no positive irritant to the eye. Therefore, CJ302 was not met GHS criteria.

Executive summary:

This test using the procedures outlined in the QPS Taiwan Study Plan for T65315008-IR which is based on the SOP for the OECD 405 (CTPS-TE00441) and OECD 405 (OECD, 2012). There were no test article effects on mortality, clinical observations and body weight. Reversible redness of conjunctivae and chemosis with score of 1 were observed within 24 hours after test article application.CJ302 was given by a single ocular application at 100 mg amount to NZW male rabbits and followed by ocular examination within 72 hours and a 4 days clinical observation period. Conjunctiva redness and chemosis with score 1 were determined within 24 hours and fully recovered. 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. The Primary Irritation Index for CJ302 was calculated to be 0.22. On the basis of the test results given above and according to Draize Dermal Classification System, the result does not meet the CLP criteria. Therefore, CJ302 is not classified.

 

Eye irritation

There were no test article effects on mortality, clinical observations and body weight. Reversible redness of conjunctivae and chemosis with score of 1 were observed within 24 hours after test article application.CJ302 was given by a single ocular application at 100 mg amount toNZW male rabbits and followed by ocular examination within 72 hours and a 4 days clinical observation period. Conjunctiva redness and chemosis with score 1 were determined within 24 hours and fully recovered. 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.