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

Eye irritation

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

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

EC Number:

943-066-4

Molecular formula:

Not applicable; this UVCB substance contains: C27H19ClN7O10S3.xLi.yNa, (x + y) = 3; 0 < (x,y) < 3 with 753.9 < MW < 802.0 g/mol (UVCB substance) and traces of NaCl.

IUPAC Name:

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

Test material form:

solid: particulate/powder

Test animals / tissue source

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

Test system

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

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal: #01

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Results 2

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

Results 3

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

Results 4

Irritation parameter:

iris score

Basis:

animal: #01, 02 and 03

Time point:

24/48 h

Score:

0

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal: #01

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Results 6

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

Results 7

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

Results 8

Irritation parameter:

chemosis score

Basis:

animal: #01

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Results 9

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

Any other information on results incl. tables

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	Normal^1
02	2410	2483	73	Normal^1
03	2327	2406	79	Normal^2

1: D1-D7

2: D1-D14

 

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

Animal I.D.	Observation point	Cornea (D/A^5)^1	Iris	Conjunctivae (R/D)^2
01	1 h^4	0/-	0	2/1
	24 h	0/-	0^3	0/0
	48 h	0/-	0^3	0/0
	72 h	0/-	0^3	0/0
	D7	-	Normal	-
02	1 h	0/-	0	2/1
	24 h	1/1	0^3	1/1
	48 h	1/1	0^3	0/0
	72 h	0/-	0^3	0/0
	D7	-	Normal	-
03	1 h	0/-	0	2/1
	24 h	1/1	0^3	1/1
	48 h	0/-	0^3	1/0
	72 h	0/-	0^3	1/0
	D7	0/-	0^3	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

Applicant's summary and conclusion

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.