5-((4-chloro-6-((8-hydroxy-3,6-disulfo-7-((2-sulfo-4-((2(sulfooxy)ethyl)sulfonyl)phenyl)diazenyl)naphthalen-1-yl)amino)-1,3,5-triazin-2-yl)amino)-4-hydroxy-3-((Z)-(3-sulfophenyl)diazenyl)naphthalene-2,7-disulfonic acid

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Justification for type of information:

data is from experimental report.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1978

Report date:

1978

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: method described in the 'Code of Federal Regulations', Title 16, Section 1500.42.

Principles of method if other than guideline:

Eye irritation test was conducted by using the given test chemical on rodents.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

octasodium 2,2'-[(2,2'-disulphonato[1,1'-biphenyl]-4,4'-diyl)bis[imino(6-chloro-1,3,5-triazine-4,2-diyl)imino(1-hydroxy-3-sulphonatonaphthalene-6,2-diyl)azo]]bisnaphthalene-1,5-disulphonate

Cas Number:

68110-30-5

Molecular formula:

C58H30Cl2N14Na8O26S8

IUPAC Name:

octasodium 2,2'-[(2,2'-disulphonato[1,1'-biphenyl]-4,4'-diyl)bis[imino(6-chloro-1,3,5-triazine-4,2-diyl)imino(1-hydroxy-3-sulphonatonaphthalene-6,2-diyl)azo]]bisnaphthalene-1,5-disulphonate

Test material form:

solid

Details on test material:

Name of the test chemical: Octasodium 2,2'-[(2,2'-disulphonato[1,1'-biphenyl]-4,4'-diyl)bis[imino(6-chloro-1,3,5-triazine-4,2-diyl)imino (1-hydroxy-3-sulphonatonaphthalene-6,2-diyl)azo]]bisnaphthalene-1,5-disulphonate
Molecular formula: C58H30Cl2N14Na8O26S8
Molecular weight: 1850.3 g/mol
Smiles Notation: [Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].c1(c(cc(cc1)Nc1nc(nc(n1)Cl)Nc1cc2cc(c(c(c2cc1)O)\N=N\c1c(c2cccc(c2cc1)S(=O)(=O)[O-])S(=O)(=O)[O-])S(=O)(=O)[O-])S(=O)(=O)[O-])c1c(cc(cc1)Nc1nc(nc(n1)Cl)Nc1cc2cc(c(c(c2cc1)O)\N=N\c1c(c2cccc(c2cc1)S(=O)(=O)[O-])S(=O)(=O)[O-])S(=O)(=O)[O-])S(=O)(=O)[O-]
InChI: 1S/C58H38Cl2N14O26S8.8Na/c59-53-65-55(61-27-7-11-31-25(19-27)21-45(105(89,90)91)47(49(31)75)73-71-39-17-15-35-37(51(39)107(95,96)97)3-1-5-41(35)101(77,78)79)69-57(67-53)63-29-9-13-33(43(23-29)103(83,84)85)34-14-10-30(24-44(34)104(86,87)88)64-58-68-54(60)66-56(70-58)62-28-8-12-32-26(20-28)22-46(106(92,93)94)48(50(32)76)74-72-40-18-16-36-38(52(40)108(98,99)100)4-2-6-42(36)102(80,81)82;;;;;;;;/h1-24,75-76H,(H,77,78,79)(H,80,81,82)(H,83,84,85)(H,86,87,88)(H,89,90,91)(H,92,93,94)(H,95,96,97)(H,98,99,100)(H2,61,63,65,67,69)(H2,62,64,66,68,70);;;;;;;;/q;8*+1/p-8/b73-71+,74-72+;;;;;;;;
Substance Type: Organic
Physical State: Solid

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Sex: male
- Weight at study initiation: 2.5 - 3.5 kg bodyweight
- Housing:were housed individually in suspended galvanized and stainless steel cages (from Cope and Cope Ltd.), measuring 0.6 x 0.6 x 0.4 m high and fitted with mesh floors and automatic watering
- Diet (e.g. ad libitum): complete pelleted rabbit diet; Diet RAG modified, from Labsure Animal Foods, Poole, Dorset; ad libitum
- Water (e.g. ad libitum): water; ad libitum
- Acclimation period:All rabbits were held for a minimum period of seven days before entering the study.
- Identification: Each animal was weighed and allocated by random selection to the appropriate test group, in which it was identified by numbered ear-tag.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Room temperature was controlled within the range 15 0 ± 2 0 C
- Photoperiod (hrs dark / hrs light):lighting was restricted to 14 hours in each period of 24 hours

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

100mg

Duration of treatment / exposure:

single exposure

Observation period (in vivo):

The eyes were examined and the grades of ocular reaction were graded at 1 hour, 24 hours, 48 hours and 72 hours after instillation

Duration of post- treatment incubation (in vitro):

no data available

Number of animals or in vitro replicates:

6 male rabbits

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not washed
- Time after start of exposure: The treated eyes were not washed after instillation of the test chemical

SCORING SYSTEM: Draize method for scoring of ocular lesions

Results and discussion

In vivo

Results

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Score:

2.6

Reversibility:

fully reversible within: 7 days

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Single ocular instillation of test chemical, without rinse, into the conjunctival sac resulted in immediate pain reactions varying from practically no initial pain i.e. a few blinks only in one animal, to moderate initial pain in two animals with rubbing of eyes with paws. Three rabbits presented an intermediate response with reflex closure of the eyes without rubbing. Subsequent eye irritation consisted of occasional minor redness and chemosis of the conjunctiva up to 24 hours after treatment in five rabbits. The sixth animal showed greater irritation, with initial discharge at one hour, grade 2 chemosis up to 48 hours, persistent grade 1 conjunctival redness to Day 7 and corneal opacity for four days, never exceeding one-half the total area and clearing by Day 7. These responses resulted in an Irritation Score of 2.6.

Any other information on results incl. tables

Scoring of Ocular responses elicited by single instillation of 100mg of the test chemical, without rinse

 

 

Animal number	Time		Hour				days			Pain evaluation class
	Region of eye	Response
			1	24	48	72	4	7	14
305	Cornea	Opacity A	0	0	0	0	0	0		1
		Area B
		Ulceration I
		Stippling II
		SCORE = A*B*C*5	0	0	0	0	0	0
	IRIS	Value A	0	0	0	0	0	0
		Score = A*5	0	0	0	0	0	0
	CONJUNCTIVA	Redness A	0	1	0	0	0	0
		Chemosis B	1	0	0	0	0	0
		Discharge C Necrosis or ulceration	0	0	0	0	0	0
		Score = 2 (A+B+C)	2	2	0	0	0	0
	Total score		2	2	0	0	0	0
027	Cornea	Opacity A	0	0	0	0	0	0		2
		Area B
		Ulceration I
		Stippling II
		SCORE = A*B*C*5	0	0	0	0	0	0
	IRIS	Value A	0	0	0	0	0	0
		Score = A*5	0	0	0	0	0	0
	CONJUNCTIVA	Redness A	0	1	0	0	0	0
		Chemosis B	0	0	0	0	0	0
		Discharge C Necrosis or ulceration	0	0	0	0	0	0
		Score = 2 (A+B+C)	0	2	0	0	0	0
	Total score		0	2	0	0	0	0
830	Cornea	Opacity A	0	0	0	0	0	0		3
		Area B		2	1	2	2
		Ulceration I
		Stippling II
		SCORE = A*B*C*5	0	10	5	10	15	15
	IRIS	Value A	0	0	0	0	0	0
		Score = A*5	0	0	0	0	0	0
	CONJUNCTIVA	Redness A	1	1	1	1	1	1
		Chemosis B	2	2	0	0	0	0
		Discharge C Necrosis or ulceration	1	0	0	0	0	0
		Score = 2 (A+B+C)	8	6	2	2	2	2
	Total score		8	16	7	17	17	0
832	Cornea	Opacity A	0	0	0	0	0	0		3
		Area B
		Ulceration I
		Stippling II
		SCORE = A*B*C*5	0	0	0	0	0	0
	IRIS	Value A	0	0	0	0	0	0
		Score = A*5	0	0	0	0	0	0
	CONJUNCTIVA	Redness A	0	0	0	0	0	0
		Chemosis B	1	0	0	0	0	0
		Discharge C Necrosis or ulceration	0	0	0	0	0	0
		Score = 2 (A+B+C)	2	0	0	0	0	0
	Total score		2	0	0	0	0	2
838	Cornea	Opacity A	0	0	0	0	0	0		2
		Area B
		Ulceration I
		Stippling II
		SCORE = A*B*C*5	0	0	0	0	0	0
	IRIS	Value A	0	0	0	0	0	0
		Score = A*5	0	0	0	0	0	0
	CONJUNCTIVA	Redness A	0	0	0	0	0	0
		Chemosis B	0	0	0	0	0	0
		Discharge C Necrosis or ulceration	0	0	0	0	0	0
		Score = 2 (A+B+C)	0	0	0	0	0	0
	Total score		0	0	0	0	0	0
981	Cornea	Opacity A	0	0	0	0	0	0		2
		Area B
		Ulceration I
		Stippling II
		SCORE = A*B*C*5	0	0	0	0	0	0
	IRIS	Value A	0	0	0	0	0	0
		Score = A*5	0	0	0	0	0	0
	CONJUNCTIVA	Redness A	0	1	0	0	0	0
		Chemosis B	1	0	0	0	0	0
		Discharge C Necrosis or ulceration	0	0	0	0	0	0
		Score = 2 (A+B+C)	2	2	0	0	0	0
	Total score		2	2	0	0	0	0
Primary irritation score									2.56

 

 

Applicant's summary and conclusion

Interpretation of results:

other: not irritating

Conclusions:

Single ocular instillation of test chemical, without rinse, into the conjunctival sac resulted in immediate pain reactions varying from practically no initial pain i.e. a few blinks only in one animal, to moderate initial pain in two animals with rubbing of eyes with paws. Three rabbits presented an intermediate response with reflex closure of the eyes without rubbing. Subsequent eye irritation consisted of occasional minor redness and chemosis of the conjunctiva up to 24 hours after treatment in five rabbits. The sixth animal showed greater irritation, with initial discharge at one hour, grade 2 chemosis up to 48 hours, persistent grade 1 conjunctival redness to Day 7 and corneal opacity for four days, never exceeding one-half the total area and clearing by Day 7. These responses resulted in an Irritation Score of 2.6. Hence, based on the observations and scores, it was considered to be not irritating to rabbit eyes.

Executive summary:

A study was performed according to method described in the 'Code of Federal Regulations', Title 16, Section 1500.42 to predict the potential for damage to the conjunctiva, cornea and iris in a single exposure of the given test chemical for indeterminate duration in the rabbit. 100 mg of the undiluted test chemical was instilled into the left eye of 6 male New Zealand White rabbits. The untreated eyes served as controls.The treated eyes remained unwashed throughout the study. The eyes were examined and the grades of ocular reaction were graded at 1 hour, 24 hours, 48 hours and 72 hours after instillation.The eyes were also evaluated for Pain upon instillation of the test chemical. The ocular reactions were graded according to the method of Draize. For each animal, the scores for the cornea, iris and conjunctiva were added for each of the 24, 48 and 72 hour time periods to give a total score/animal/time period. Then the total scores so obtained were added together and divided by 18.The resultant value was the Irritation Score. Single ocular instillation of test chemical, without rinse, into the conjunctival sac resulted in immediate pain reactions varying from practically no initial pain i.e. a few blinks only in one animal, to moderate initial pain in two animals with rubbing of eyes with paws. Three rabbits presented an intermediate response with reflex closure of the eyes without rubbing. Subsequent eye irritation consisted of occasional minor redness and chemosis of the conjunctiva up to 24 hours after treatment in five rabbits. The sixth animal showed greater irritation, with initial discharge at one hour, grade 2 chemosis up to 48 hours, persistent grade 1 conjunctival redness to Day 7 and corneal opacity for four days, never exceeding one-half the total area and clearing by Day 7. These responses resulted in an Irritation Score of 2.6. Hence, based on the observations and scores, it  was considered to be not irritating to rabbit eyes.