Registration Dossier

Administrative data

Description of key information

Skin Irritation:

On the basis of available studies for the structurally similar read across substances, the weight of evidence approach was applied to assess the dermal irritation potential of Tetrasodium 3-[[5-[[4-chloro-6-[[3-[[2-(sulphonatooxy)ethyl]sulphonyl]phenyl]amino]-1,3,5-triazin-2-yl]amino]-2-sulphonatophenyl] azo]-4-hydroxy-5-[(1-oxopropyl)amino]naphthalene-2,7-disulphonate.Tetrasodium 3-[[5-[[4-chloro-6-[[3-[[2-(sulphonatooxy)ethyl]sulphonyl]phenyl]amino]-1,3,5-triazin-2-yl]amino]-2-sulphonatophenyl] azo]-4-hydroxy-5-[(1-oxopropyl)amino]naphthalene-2,7-disulphonate was estimated to be not irritating to skin.

Eye Irritation:

On the basis of available studies for the structurally similar read across substances, the weight of evidence approach was applied to assess the ocular irritation potential of Tetrasodium 3-[[5-[[4-chloro-6-[[3-[[2-(sulphonatooxy)ethyl]sulphonyl]phenyl]amino]-1,3,5-triazin-2-yl]amino]-2-sulphonatophenyl] azo]-4-hydroxy-5-[(1-oxopropyl)amino]naphthalene-2,7-disulphonate.Tetrasodium 3-[[5-[[4-chloro-6-[[3-[[2-(sulphonatooxy)ethyl]sulphonyl]phenyl]amino]-1,3,5-triazin-2-yl]amino]-2-sulphonatophenyl] azo]-4-hydroxy-5-[(1-oxopropyl)amino]naphthalene-2,7-disulphonate was estimated to be not irritating to rabbit eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Weight of evidence based on the structurally similar chemicals
Justification for type of information:
Weight of evidence based on the structurally similar chemicals
Reason / purpose:
read-across: supporting information
Reason / purpose:
read-across: supporting information
Qualifier:
according to
Guideline:
other: Weight of evidence based on structurally similar chemicals
Principles of method if other than guideline:
The weight of evidence report has been prepared based on the read across substances identified based on structural and functional similarity to assess the ocular irritation potential of Tetrasodium 3-[[5-[[4-chloro-6-[[3-[[2-(sulphonatooxy)ethyl]sulphonyl]phenyl]amino]-1,3,5-triazin-2-yl]amino] -2-sulphonatophenyl]azo]-4-hydroxy-5-[(1-oxopropyl)amino]naphthalene-2,7-disulphonate
GLP compliance:
not specified
Species:
rat
Strain:
Sprague-Dawley
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: National Institute of Biosciences, Pune.
- Females nulliparous and non-pregnant: No data available
- Age at study initiation: Young adult male and female rats aged between 8 – 12 weeks were used.
- Weight at study initiation: The weight range of approximately 216.9 to 251.9 grams at initiation of dosi
ng.
Body weights at the start :
Male
Mean : 241.18 g (= 100 %)
Minimum : 235.8 g (- 2.23 %)
Maximum : 251.9 g (+ 4.44 %)
Total No. of animals : 5
Female
Mean : 221.08 g (= 100 %)
Minimum : 216.9 g (- 1.89 %)
Maximum : 228.5 g (+ 3.36 %)
Total No. of animals : 5
- Identification: Each rat was individually identified by the cage number.
- Fasting period before study: No data available
- Housing: The rats were individually housed in polycarbonate cages with paddy husk as bedding.
- Diet (e.g. ad libitum): Rodent feed supplied by the Nutrivet Life Sciences, Pune, was provided ad libitum
from individual feeders.
- Water (e.g. ad libitum): Water was provided ad libitum from individual bottles attached to the cages. All water was from a local source and passed through the reverse osmosis membrane before use.
- Acclimation period: 5 days.
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
2000 mg/kg bw
Duration of treatment / exposure:
24 hours
Observation period:
14 days
Number of animals:
3
Details on study design:
The study is based on weight of evidence approach from the read across values
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
14 d
Score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No signs of irritation observed
Interpretation of results:
other: not irritating
Conclusions:
On the basis of available studies for the structurally similar read across substances, the weight of evidence approach was applied to assess the dermal irritation potential of Tetrasodium 3-[[5-[[4-chloro-6-[[3-[[2-(sulphonatooxy)ethyl]sulphonyl]phenyl]amino]-1,3,5-triazin-2-yl]amino]-2-sulphonatophenyl] azo]-4-hydroxy-5-[(1-oxopropyl)amino]naphthalene-2,7-disulphonate.Tetrasodium 3-[[5-[[4-chloro-6-[[3-[[2-(sulphonatooxy)ethyl]sulphonyl]phenyl]amino]-1,3,5-triazin-2-yl]amino]-2-sulphonatophenyl] azo]-4-hydroxy-5-[(1-oxopropyl)amino]naphthalene-2,7-disulphonate was estimated to be not irritating to skin.
Executive summary:

Based on the available studies for the structurally similar read across chemicals, weight of evidence approach was applied to assess the dermal irritation potential of Tetrasodium 3-[[5-[[4 -chloro-6-[[3-[[2-(sulphonatooxy)ethyl]sulphonyl]phenyl]amino]-1,3,5-triazin-2-yl]amino]-2-sulphonatophenyl] azo]-4-hydroxy-5-[(1-oxopropyl)amino]naphthalene-2,7-disulphonate.

Experimental studies were designed and conducted to determine the dermal reaction profile of the structurally similar read across chemicals in Sprague Dawley rats. The study was performed as per OECD Guidelines 402 and complying to the GLP procedures. Ten rats (5 male and 5 female) were used for conducting dermal irritation /corrosion study.

The animals were kept in their cages for at least 5 days prior to administration for acclimatization to the laboratory condition and after acclimatization period, animals were randomly selected. Approximately 24 hours before application, the hair of each rat was closely clipped from the trunk (dorsal surface and sides from scapular to pelvic area) with an electric clipper, so as to expose at least 10% of the body surface area. The test item was applied directly onto the exposed skin of the animal, taking care to spread the test item evenly over the entire area of approximately 10% of the total body surface area or as much of the area as can reasonably be covered. The test item was held in contact with the skin using a porous gauze dressing and non irritating tape around the animal to cover the exposure site for first 24 hours exposure period. Elizabethan collar was placed on each animal for first 24 hours after application of the test item.

 

These collars prevent ingestion of test item. Following 24 hours of exposure, the wrapping was removed and the test site wiped free of excess test item. Distilled water was used to remove residual test item.The test chemicals were applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. The overall irritation score of the structurally similar read across chemicals were determined to be 0 and no erythema and edema (skin irritation) were observed at the end of 14 days observation period after patch removal.

 

Hence, it was concluded that the structurally similar read across chemicals were Non-Irritating to the skin of Sprague Dawley rats under the experimental conditions tested and classified as “Category-Not Classified” as per CLP Classification.

 

Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that the target chemical will also tend to behave in a similar that of the read across substances. Therefore the target chemical was estimated to be not irritating to skin and it can be further classified under the category “Not Classified” as per CLP regulation.

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:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Weight of evidence based on structurally similar substances
Justification for type of information:
Weight of evidence based on structurally similar substances
Reason / purpose:
read-across: supporting information
Reason / purpose:
read-across: supporting information
Qualifier:
according to
Guideline:
other: Weight of evidence based on structurally similar substances
Principles of method if other than guideline:
The weight of evidence report has been prepared based on the read across substances identified based on structural and functional similarity to assess the ocular irritation potential of Tetrasodium 3-[[5-[[4-chloro-6-[[3-[[2-(sulphonatooxy)ethyl]sulphonyl]phenyl]amino]-1,3,5-triazin-2-yl]amino]-2-sulphonatophenyl] azo]-4-hydroxy-5-[(1-oxopropyl)amino]naphthalene-2,7-disulphonate
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of test material: Tetrasodium 3-[[5-[[4-chloro-6-[[3-[[2-(sulphonatooxy)ethyl]sulphonyl]phenyl]amino]-1,3,5-triazin-2-yl]amino] -2-sulphonatophenyl]azo]-4-hydroxy-5-[(1-oxopropyl)amino]naphthalene-2,7-disulphonate
- IUPAC name: Tetrasodium 3-[[5-[[4-chloro-6-[[3-[[2-(sulphonatooxy)ethyl]sulphonyl]phenyl]amino]-1,3,5-triazin-2-yl]amino]-2-sulphonatophenyl] azo]-4-hydroxy-5-[(1-oxopropyl)amino]naphthalene-2,7-disulphonate
- Molecular formula: C30H27ClN8O17S5.4Na
- Molecular weight: 1055.29 g/mole
- Smiles :[Na+].[Na+].[Na+].[Na+].c1c(c(c(c2c(cc(cc12)S(=O)(=O)[O-])NC(CC)=O)O)\N=N\c1c(ccc(c1)Nc1nc(nc(n1)Cl)Nc1cc(ccc1)S(=O)(=O) CCOS(=O)(=O)[O-])S(=O)(=O)[O-])S(=O)(=O)[O-]
- Inchl: 1S/C30H27ClN8O17S5.4Na/c1-2-24(40)34-21-14-19(58(44,45)46)10-15-11-23(60(50,51)52)26(27(41)25(15)21)39-38-20-13-17(6-7-22(20) 59(47,48)49)33-30-36-28(31)35-29(37-30)32-16-4-3-5-18(12-16)57(42,43)9-8-56-61(53,54)55;;;;/h3-7,10-14,41H,2,8-9H2,1H3,(H,34,40)(H,44,45,46)(H,47,48,49)(H,50,51,52)(H,53,54,55)(H2,32,33,35,36,37);;;;/q;4*+1/p-4/b39-38+;;;;
- Substance type: Organic
- Physical state: Solid crystalline
Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
no data available
Vehicle:
other: aqueous suspension; water
Controls:
not specified
Amount / concentration applied:
1. 2 instillations of 10% (0.2ml)
2. 0.2 ml of a 10% aqueous solution (20 mg)
Duration of treatment / exposure:
1. The test substance was installed into conjunctival sac of rabbits 5 times per week for 4 weeks.
2. test material was applied twice daily, five times weekly
Observation period (in vivo):
1. 4 weeks
2. 4 weeks
Duration of post- treatment incubation (in vitro):
no data available
Number of animals or in vitro replicates:
1. not specified
2. 6 or more albino rabbits
Details on study design:
The study is based on weight of evidence approach from the read across values
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 4 weeks
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No signs of irritation observed
Interpretation of results:
other: not irritating
Conclusions:
On the basis of available studies for the structurally similar read across substances, the weight of evidence approach was applied to assess the ocular irritation potential of Tetrasodium 3-[[5-[[4-chloro-6-[[3-[[2-(sulphonatooxy)ethyl]sulphonyl]phenyl]amino]-1,3,5-triazin-2-yl]amino]-2-sulphonatophenyl] azo]-4-hydroxy-5-[(1-oxopropyl)amino]naphthalene-2,7-disulphonate.Tetrasodium 3-[[5-[[4-chloro-6-[[3-[[2-(sulphonatooxy)ethyl]sulphonyl]phenyl]amino]-1,3,5-triazin-2-yl]amino]-2-sulphonatophenyl] azo]-4-hydroxy-5-[(1-oxopropyl)amino]naphthalene-2,7-disulphonate was estimated to be not irritating to rabbit eyes.
Executive summary:

Based on the available studies for the structurally similar read across chemicals, weight of evidence approach was applied to assess the ocular irritation potential of Tetrasodium 3-[[5-[[4 -chloro-6-[[3-[[2-(sulphonatooxy)ethyl]sulphonyl]phenyl]amino]-1,3,5-triazin-2-yl]amino]-2-sulphonatophenyl] azo]-4-hydroxy-5-[(1-oxopropyl)amino]naphthalene-2,7-disulphonate.

The local eye irritative potential of the structurally similar read across chemical was investigated in rabbits’ eye to assess the degree of eye irritancy caused by the chemical.

Each rabbit received 2 installations of 0.2 ml of a 10% aqueous suspension of the test chemical into the conjunctival sac of rabbits 5 times per week for 4 weeks. The chemical produced only minimal irritative effects after 2 hours which could not confirmed the irritation potential. Hence, on the basis of findings, the test chemical can be considered as not irritating to the rabbits’ eye.

 

The above result is supported by a study conducted to determine the irritation potential of another structurally similar read across chemical on rabbit eyes.

0.2 ml of a 10% aqueous solution (20 mg) or suspension of the test material was applied twice daily, five times weekly, for four weeks to the conjunctival sac of one eye of each of a group of six or more albino rabbits (40 applications). One hour after each application, the eyes were examined for evidence of staining and the irritation was scored according to Draize.

The overall irritation score after 20 days of observation was 0.0. Hence, the test chemical was considered to be not irritating to rabbit eyes.

Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that the target chemical will also tend to behave in a similar that of the read across substances. Therefore the target chemical was estimated to be not irritating to eyes and it can be further classified under the category “Not Classified” as per CLP regulation.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

The results of the experimental studies from the structurally similar read across substances indicate a possibility that Tetrasodium 3-[[5-[[4-chloro-6-[[3-[[2-(sulphonatooxy)ethyl]sulphonyl]phenyl]amino]-1,3,5-triazin-2-yl]amino]-2-sulphonatophenyl] azo]-4-hydroxy-5-[(1-oxopropyl)amino]naphthalene-2,7-disulphonate can be not irritating to skin and eyes.

Hence by applying the weight of evidence approach, Tetrasodium 3-[[5-[[4-chloro-6-[[3-[[2-(sulphonatooxy)ethyl]sulphonyl]phenyl]amino]-1,3,5-triazin-2-yl]amino]-2-sulphonatophenyl] azo]-4-hydroxy-5-[(1-oxopropyl)amino]naphthalene-2,7-disulphonate can be considered to be not irritating to skin and eyes. It can be classified under the category “Not Classified” as per CLP regulation.