1-amino-4-({3-[(4-chloro-6-{[(3 or 4)-sulfophenyl]amino}-1,3,5-triazin-2-yl)amino]-2,4,6-trimethyl-5-sulfophenyl}amino)-9,10-dioxo-9,10-dihydroanthracene-2-sulfonic 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 April 15, 2016 to June 01, 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

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:

trilithium(1+) trisodium 1-amino-4-{[3-({4-chloro-6-[(3-sulfonatophenyl)amino]-1,3,5-triazin-2-yl}amino)-2,4,6-trimethyl-5-sulfonatophenyl]amino}-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate 1-amino-4-{[3-({4-chloro-6-[(4-sulfonatophenyl)amino]-1,3,5-triazin-2-yl}amino)-2,4,6-trimethyl-5-sulfonatophenyl]amino}-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate

Molecular formula:

Not applicable; this UVCB substance contains: C32H23ClN7O11S3.xLi.yNa, (x + y) = 3; 0 < (x,y) < 3 with 834.0 < MW < 882.1 g/mol (UVCB substance), C38H28N8O14S4.xLi.yNa, (x + y) = 4; 0 < (x,y) < 4 with 976.6 < MW < 1040.8 g/mol (UVCB substnace), and traces of NaCl and Na2SO4.

IUPAC Name:

trilithium(1+) trisodium 1-amino-4-{[3-({4-chloro-6-[(3-sulfonatophenyl)amino]-1,3,5-triazin-2-yl}amino)-2,4,6-trimethyl-5-sulfonatophenyl]amino}-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate 1-amino-4-{[3-({4-chloro-6-[(4-sulfonatophenyl)amino]-1,3,5-triazin-2-yl}amino)-2,4,6-trimethyl-5-sulfonatophenyl]amino}-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate

Test material form:

solid: particulate/powder

Remarks:

migrated information: 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 at study initiation: 4-5 months
- Weight at study initiation: 2946-3750 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): 100 mg

Duration of treatment / exposure:

1 hr

Observation period (in vivo):

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

Number of animals or in vitro replicates:

three

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

mean of 2 higher reacted ones

Time point:

24/48/72 h

Score:

1.5

Max. score:

2

Reversibility:

fully reversible within: 14 day

Remarks on result:

probability of weak irritation

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

mean of 2 higher reacted ones

Time point:

24/48/72 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 14 d

Remarks on result:

probability of weak irritation

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

mean of 2 higher reacted ones

Time point:

24/48/72 h

Score:

2.35

Max. score:

3

Reversibility:

fully reversible within: 14 d

Remarks on result:

probability of mild irritation

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

mean of 2 higher reacted ones

Time point:

24/48/72 h

Score:

1.5

Max. score:

2

Reversibility:

fully reversible within: 14 d

Remarks on result:

probability of weak 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)	Clinical observation
	D1	D4	D4-D1
7	3750	3772	22	Normal
8	2966	2876	-90	Normal
9	2946	2888	-58	Normal

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

Animal ID	7					8										9
	Score on each observation point
	1 hr	24 hr	48 hr	72 hr	7 day	1 hr	24 hr		48 hr		72 hr		7 day		14 day	1 hr	24 hr	48 hr	72 hr	7 day
Cornea
Degree of density	0	0	0	0	0	1	2		1		1		0		0	1	2	2	1	0
Area^1of opacity	0	0	0	0	0	3	3		1		1		0		0	3	2	1	1	0
Iris	0	0^2	0^2	0^2	0^2	0	1^2		0^2		0^2		0^2		0^2	0	1^2	0^2	0^2	0^2
Conjunctive
Redness	0	2	1	2	0	2	3		3		3		1		0	2	2	1	2	0
Chemosis	2	1	0	0	0	3	2		2		1		0		0	3	2	1	1	0

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

2: Iris discoloration

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

According to OECD 405 test method, CJ304 showed that a positive irritant to the eye and reversible. Therefore, CJ304 was categorized as irritant to eye (Category 2) based on GHS criteria.

Executive summary:

This test using the procedures outlined in the QPS Taiwan Study Plan for T65315009-IR which is based on the SOP for the OECD 405 (CTPS-TE00441) and OECD 405 (OECD, 2012).There were no effects on mortality.Slight body weight decreased was observed but all animals were clinically normal. Grade 2 corneal opacity in over 50% of area, grade 1 hyperemia of iris and grade 3 diffused redness and eversion of conjunctiva were observed in rabbits during 72 h after dosing.Until D14, all eye irritation effects were not observed. Moreover, iris discoloration was observed.CJ304 was given by a single ocular application at 100 mg amount to NZW 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 articlewas judged as a positive irritant to the eye.