7-[{4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-2-(carbamoylamino)phenyl}diazenyl]naphthalene-1,3,6-trisulfonic acid, lithium sodium salts

Endpoint summary

Description of key information

Skin irritation

The Primary Irritation Index (PII) of CJ312 was 0 and CJ 312 was categorized as non skin irritant (OECD TG404).

 

Eye irritation

CJ 312was 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 March 09, 2016 to June 01, 2016

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: the animal health research institute, council of agriculture, executive yuan
- Age at study initiation: approximately 4 to 5 months
- Weight at study initiation: 3422 to 3462 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)

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
10	3422	3706	284	Normal
11	3428	3607	179	Normal
12	3462	3627	165	Normal

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

Animal ID	10				11				12
	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	0	0	0	0	1	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
PII**	0

* 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 PII for CJ312 in intact skin was 0 and CJ312 was categorized as non-irritant. CJ312 was not met classification on GHS criteria.

Executive summary:

This test using the procedures outlined in the QPS Taiwan Study Plan for T65315018-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. Score 1 erythema was observed in one animal at 1 hour after patch removal. The Primary Irritation Index for CJ312 was calculated to be 0.On the basis of the test results given above and according to Draize Dermal Classification System, the response of CJ312 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 28, 2016 to June 01, 2016

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: 3124-4041 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 - <= 1

Max. score:

0.67

Reversibility:

fully reversible within: 72 hours

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. 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
16	3879	3913	34	Normal
17	3124	3118	-6	Normal
18	4041	4049	-8	Normal

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

Animal ID	16				17				18
	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	0^1	0^1	0^1	0	0^1	0^1	0^1	0	0^1	0^1	0^1	0
Conjunctive
Redness	1	0	0	0	1	0	0	0	1	1	1	0
Chemosis	0	0	0	0	0	0	0	0	0	0	0	0

1: Iris discoloration

Interpretation of results:

GHS criteria not met

Conclusions:

According to OECD 405 test method, CJ312 showed that no positive irritant to the eye. Therefore, CJ312 was not met GHS criteria.

Executive summary:

This test using the procedures outlined in the QPS Taiwan Study Plan for T65315012-IR which is based on the SOP for the OECD 405 (CTPS-TE00441) and OECD 405 (OECD, 2012).There were no CJ312 effects on mortality, clinical observations and body weight.Reversible redness of conjunctivae with score of 1 was observed within 48 hours after CJ312 application. Moreover, iris discoloration was observed.CJ312 was given by a single ocular application at 100 mg amount toNZW male rabbits and followed by ocular examinationwith 72 hours and a 4days clinical observation period. Conjunctiva redness with score 1 was determined within 48 hours and filly recovered. On the basis of the test results given above, the response of CJ312was 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. Score 1 erythema was observed in one animal at 1 hour after patch removal. The Primary Irritation Index for CJ312 was calculated to be 0.On the basis of the test results given above and according to Draize Dermal Classification System, the response of CJ312 was categorized as non-irritant.

 

Eye irritation

There were no CJ312 effects on mortality, clinical observations and body weight.Reversible redness of conjunctivae with score of 1 was observed within 48 hours after CJ312 application. Moreover, iris discoloration was observed.CJ312 was given by a single ocular application at 100 mg amount toNZW male rabbits and followed by ocular examinationwith 72 hours and a 4days clinical observation period. Conjunctiva redness with score 1 was determined within 48 hours and filly recovered. On the basis of the test results given above, the response of CJ312 was not judged as a positive irritant to the eye.