5-({4-chloro-6-[ethyl(phenyl)amino]-1,3,5-triazin-2-yl}amino)-4-hydroxy-3-[(1-sulfo-2-naphthyl)diazenyl]naphthalene-2,7-disulfonic acid, lithium sodium salts

Endpoint summary

Description of key information

Skin irritation

The Primary Irritation Index (PII) of CJ306 was 0 and CJ 306 was categorized as non-irritant to the skin (OECD TG404).

 

Eye irritation

CJ 306 was 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 April 26, 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 3 to 4 months
- Weight at study initiation: 2646 to 3014 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

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 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:

primary dermal irritation index (PDII)

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Table 1. Individual Body Weights and Clinical Observations Table 1. Individual Body Weights and Clinical Observations

Animal ID	Body weight (g)		Body weight change (g)	Clinical observation
	D1	D4	D4-D1
1	2646	2769	123	Normal
2	2786	2853	67	Normal
3	3014	3046	32	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	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
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 CJ306 in intact skin was 0 and CJ306 was categorized as non-irritant. Therefore, CJ306 was not met classification on GHS criteria.

Executive summary:

This test using the procedures outlined in the QPS Taiwan Study Plan for T65315016-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. All scores of erythema and edema were 0 during 72 hours after patch removal. The Primary Irritation Index for CJ306 was calculated to be 0. On the basis of the test results given above and according to Draize Dermal Classification System, the response of CJ306 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 15, 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: 2918-3614 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 hrs

Observation period (in vivo):

1 hr, 24 hr, 48 hr, 72 hr, 7 day, 14 day

Number of animals or in vitro replicates:

Three

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

2 more reaction ones

Time point:

24/48/72 h

Score:

1.9

Max. score:

2

Reversibility:

fully reversible within: 14 day

Remarks on result:

positive indication of irritation

Irritation parameter:

iris score

Basis:

mean

Remarks:

2 more reation ones

Time point:

24/48/72 h

Score:

0.5

Max. score:

1

Reversibility:

fully reversible within: 72 hr

Remarks on result:

probability of weak irritation

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

2 higher rection ones

Time point:

24/48/72 h

Score:

2.3

Max. score:

3

Reversibility:

fully reversible within: 14 days

Remarks on result:

positive indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

2 more reaction ones

Time point:

24/48/72 h

Score:

2.6

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

positive 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	2957	3011	54	Normal
11	2918	2913	-5	Normal
12	3614	3661	47	Normal

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

Animal ID	10						11						12
	Score on each observation point
	1 hr	24hr	48hr	72 hr	7 day	14 day	1 hr	24 hr	48 hr	72 hr	7 day	14 day	1 hr	24 hr	48 hr	72 hr	7 day	14 day
Cornea
Degree of density	3	2	2	2	1	0	0	1	2	2	2	0	0	0	0	0	0	0
Area^1of opacity	3	4	1	3	2	0	0	2	1	2	2	0	0	0	0	0	0	0
Iris	NA	1	0	0	0^2	0	0	1	1	0^2	0^2	0	0	0^2	0	0^2	0^2	0
Conjunctiva
Redness	2	3	2	2	1	0	0	3	3	1	1	0	1	1	1	1	1	0
Chemosis	2	4	4	2	0	0	1	3	2	1	1	0	2	1	1	0	1	0

¹:Score 1: 1/4 (or less) not zero; Score 2: greater than 1/4 but less than 1/2; Score 3: greater that 1/2, but less than 3/4; Score 4: greater than 3/4, up to whole area.

²:Iris discoloration

NA: the iris could not be observed since cornea opacity

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

According to OECD 405 test method, CJ306 showed that positive irritant to the eye and reversible. Therefore, CJ306 was categorized as irritating to eyes (Category 2) base on GHS criteria.

Executive summary:

This test using the procedures outlined in the QPS Taiwan Study Plan for T65315010-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.CJ306 was given by a single ocular application at 100 mg amount toNZW male rabbits andfollowed by ocular examination and clinical observation for 14 days. Reversible corneal opacity, hyperemia of iris, and conjunctiva redness and chemosis were observed within 14 days.On the basis of the test results given above, the response of the test article was judged as a positive irritant to the eye.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (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 CJ306 was calculated to be 0. On the basis of the test results given above and according to Draize Dermal Classification System, the response of CJ306 was categorized as non-irritant.

 

Eye irritation

There were no test article effects on mortality, clinical observations and body weight.CJ306 was given by a single ocular application at 100 mg amount toNZW male rabbits and followed by ocular examination and clinical observation for 14 days. Reversible corneal opacity, hyperemia of iris, and conjunctiva redness and chemosis were observed within 14 days.On the basis of the test results given above, the response of the test article was judged as a positive irritant to the eye.