Registration Dossier

Administrative data

Description of key information

Skin Irritation

By applying the weight of evidence approach, the test chemical can be considered to be not irritating to skin. Comparing the annotations with criteria of CLP regulation, the test chemical can be classified under the category "Not Classified"

Eye Irritation

By applying the weight of evidence approach, the test chemical can be considered to be not irritating to eyes. Comparing the annotations with criteria of CLP regulation, the test chemical can be classified under the category "Not Classified"

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:
data from handbook or collection of data
Remarks:
weight of evidence approach based on similar test chemicals
Justification for type of information:
Weight of evidence approach based on similar test chemicals
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
other: Weight of evidence based on similar test chemicals
Principles of method if other than guideline:
Weight of evidence based on similar test chemicals
GLP compliance:
not specified
Specific details on test material used for the study:
- IUPAC Name: 2-[[6-[[4-Chloro-6-[[4-[[2-(sulfooxy)ethyl]sulfonyl]phenyl]amino]-1,3,5-triazin-2-yl]amino]-1-hydroxy-3-sulfo-2-naphthalenyl]azo]-1,5-naphthalenedisulfonic acid tetrasodium salt
- Mol. formula: C31H20ClN7Na4O16S5
- Molecular Weight: 1034.275 g/mole
- InChI: 1S/C31H24ClN7O16S5.4Na/c32-29-35-30(33-17-4-7-19(8-5-17)56(41,42)13-12-55-60(52,53)54)37-31(36-29)34-18-6-9-20-16(14-18)15-25(58(46,47)48)26(27(20)40)39-38-23-11-10-21-22
(28(23)59(49,50)51)2-1-3-24(21)57(43,44)45;;;;/h1-11,14-15,40H,12-13H2,(H,43,44,45)(H,46,47,48)(H,49,50,51)(H,52,53,54)(H2,33,34,35,36,37);;;;/q;4*+1/p-4/b39-38+;;;;
- Smiles:c1cc2c(ccc(c2S(=O)(=O)[O-])N=Nc3c(cc4cc(ccc4c3O)Nc5nc(nc(n5)Cl)Nc6ccc(cc6)S(=O)(=O)CCOS(=O)(=O)[O-])S(=O)(=O)[O-])c(c1)S(=O)(=O)[O-].[Na+].[Na+].[Na+].[Na+]
Species:
other: rat, rabbit
Strain:
not specified
Type of coverage:
other: 1. occlusive; 2. semi-occlusive; 3. Entire inner surface of one ear
Preparation of test site:
other: 1. clipped; 2. clipped; 3. A colony of rabbits that had genetically good ears and which were free from mites were used for the assay
Vehicle:
other: 1. undliuted; 2. undiluted; 3. The test chemical was mixed in propylene glycol at a 9 to 1 dilution for testing.
Controls:
not specified
Amount / concentration applied:
1. 500gm (0.5g
2. 2000 mg/kg body weight
3.Dose of 1ml of the test material was applied once daily for five days per week for 2 weeks
Duration of treatment / exposure:
1. 4 hours
2. 24 hours
3.2 weeks
Observation period:
1. 60 min., 24, 48 and 72 hours till 14 days after application
2. 14 days
3. 2 weeks
Number of animals:
1. 3
2. 5
3. 3
Details on study design:
The data is based on weight of evidence approach based on various test chemicals
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:
By applying the weight of evidence approach, the test chemical can be considered to be not irritating to skin. Comparing the annotations with criteria of CLP regulation, the test chemical can be classified under the category "Not Classified".
Executive summary:

The skin irritation potential of the test chemical was assessed based on the available results from the various test chemicals.

A dermal irritation study was conducted on New Zealand white rabbits in accordance with OECD 404 to assess the irritation parameter of the test chemical. 3 female New Zealand White rabbits were used for the study. The animals were prepared 24 hours prior to application of test product. The furs from the dorsal area of trunk of animals were removed with electric clippers exposing an area measuring approximately 6 cm2 of body surface area of animal. The care was taken such that abrasion penetrated the Stratum corneum only and not dermis. 500gm (0.5g) of test compound was applied on a small area (approximately 6 cm2) of intact skin site. Each site of application was covered with impervious dressing which was secured in position with adhesive tape. The intact skin site of application of each animal was observed for signs of erythema and oedema at 60 min., 24, 48 and 72 hours after application and the responses were scored according to Draize method.

The Primary Irritation Index (PII) for the test chemical after 14 days of observation was 0.0.Also, the test chemical did not produce pain and any clinical signs of toxicity throughout the examination period of 14 days.

Hence, under the test conditions, the test chemical can be concluded to be not irritating to New Zealand White rabbit skin.

This is supported by the results of a study designed and conducted to determine the dermal reaction profile of the test chemical 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 chemical was 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. Also, the erythema and edema score of rats was calculated as 0. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days. Animals exhibited normal body weight gain through the study period of 14 days. Gross pathological examination did not reveal any abnormalities attributable to the treatment.

Thus it can be concluded that the test chemical can be considered to be not irritating to skin and classified under "Not Classified" category.

 

These results are further supported by a test performed using a single rabbit ear to indicate the Comedogenicity and irritancy of the test chemical. The test chemical was mixed in propylene glycol at a 9 to 1 dilution for testing unless otherwise indicated (10% concentration). A colony of New Zealand albino rabbits that have genetically good ears and free from mites were used. Three rabbits, weighing two to three kilograms, were used for each assay. Animals were housed singly in suspended cages and fed Purina Rabbit Chow and water ad libitum. Animals were maintained on a 12-hour light and 12-hour dark cycle. A dose of 1 ml of the test material was applied and spread once daily to the entire inner surface of once for five days per week for two weeks. The opposite untreated ear of each animal served as an untreated control.

The irritancy produced by repeated application of the chemical on the surface epidermis in the rabbit ear is evaluated on a scale of 0 to 5. The grades are summarized as follows:

 0 = No irritation; 1 = few scales, no Erythema; 2 = diffuse scaling, no Erythema; 3 = Generalized scaling with Erythema; 4 = Scaling, Erythema and Edema; 5 = Epidermal necrosis and slough.

The test chemical falls under Grade 0 (no irritation observed). Hence it can be concluded that the test chemical was not irritating to rabbit ears.

By applying the weight of evidence approach, the test chemical can be considered to be not irritating to skin. Comparing the annotations with criteria of CLP regulation, the test chemical can be classified under the category "Not Classified".

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:
data from handbook or collection of data
Remarks:
Weight of evidence approach based on various test chemicals
Justification for type of information:
Weight of evidence approach based on various test chemicals
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
other: Weigrh of evidence approach based on various test chemicals
Principles of method if other than guideline:
Weigrh of evidence approach based on various test chemicals
GLP compliance:
not specified
Species:
rabbit
Strain:
not specified
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
1. 0.1g
2. 0.2 ml of a 10% aqueous suspension
Duration of treatment / exposure:
1. single
2. 5 times per week for 4 weeks
Observation period (in vivo):
1. 1, 24, 48 and 72 hours
2. 4 weeks
Duration of post- treatment incubation (in vitro):
no data available
Number of animals or in vitro replicates:
1. 3
2. number not specified
Details on study design:
The data is based on weight of evidence approach based on various test chemicals
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
72 h
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:
By applying the weight of evidence approach, the test chemical can be considered to be not irritating to eyes. Comparing the annotations with criteria of CLP regulation, the test chemical can be classified under the category "Not Classified"
Executive summary:

The eye irritation potential of the test chemical was assessed based on the available results from the various test chemicals.

An ocular irritation study was conducted on New Zealand white rabbits in accordance with OECD 405 to assess the irritation parameter of the test chemical. 3 female New Zealand White rabbits were used for the study. 0.1g of the undiluted test chemical was instilled in the conjunctival sac of rabbits after gently pulling the lower lid away from the eyeball. The other eye which remained untreated served as a control. The ocular lesions were evaluated at 1, 24, 48 and 72 hours after the treatment. The grades of ocular reactions (conjunctiva, cornea and iris) were recorded at each observation. To determine the reversibility of the effect the animals were observed normally for 21 days. Any other lesions in the eye viz pannus, staining were observed and scored accordingly. Examination of reactions was facilitated by use of biomicroscope and hand slit lamp. Individual animal weights before and during the study was observed.

The overall irritation index of the test chemical was 0.0 after 72 hours.

Also the test chemical did not produce any clinical signs of toxicity throughout the examination period of 21 days.

Hence, under the test conditions, the test chemical can be concluded to be not irritating to New Zealand White rabbit eyes.

This is supported by the results of a study performed to determine the local eye irritative potential of test chemical in rabbits’ eyes.

Rabbits received(number not specified) 2 installation 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 confirm the irritation potential. Hence, on the basis of findings the test chemical can be considered as not irritating to the rabbits’ eye.

By applying the weight of evidence approach, the test chemical can be considered to be not irritating to eyes. Comparing the annotations with criteria of CLP regulation, the test chemical can be classified under the category "Not Classified"

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin Irritation

The skin irritation potential of the test chemical was assessed based on the available results from the various test chemicals.

A dermal irritation study was conducted on New Zealand white rabbits in accordance with OECD 404 to assess the irritation parameter of the test chemical. 3 female New Zealand White rabbits were used for the study. The animals were prepared 24 hours prior to application of test product. The furs from the dorsal area of trunk of animals were removed with electric clippers exposing an area measuring approximately 6 cm2 of body surface area of animal. The care was taken such that abrasion penetrated the Stratum corneum only and not dermis. 500gm (0.5g) of test compound was applied on a small area (approximately 6 cm2) of intact skin site. Each site of application was covered with impervious dressing which was secured in position with adhesive tape. The intact skin site of application of each animal was observed for signs of erythema and oedema at 60 min., 24, 48 and 72 hours after application and the responses were scored according to Draize method.

The Primary Irritation Index (PII) for the test chemical after 14 days of observation was 0.0. Also, the test chemical did not produce pain and any clinical signs of toxicity throughout the examination period of 14 days.

Hence, under the test conditions, the test chemical can be concluded to be not irritating to New Zealand White rabbit skin.

This is supported by the results of a study designed and conducted to determine the dermal reaction profile of the test chemical 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 chemical was 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. Also, the erythema and edema score of rats was calculated as 0. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days. Animals exhibited normal body weight gain through the study period of 14 days. Gross pathological examination did not reveal any abnormalities attributable to the treatment.

Thus it can be concluded that the test chemical can be considered to be not irritating to skin and classified under "Not Classified" category.

 

These results are further supported by a test performed using a single rabbit ear to indicate the Comedogenicity and irritancy of the test chemical. The test chemical was mixed in propylene glycol at a 9 to 1 dilution for testing unless otherwise indicated (10% concentration). A colony of New Zealand albino rabbits that have genetically good ears and free from mites were used. Three rabbits, weighing two to three kilograms, were used for each assay. Animals were housed singly in suspended cages and fed Purina Rabbit Chow and water ad libitum. Animals were maintained on a 12-hour light and 12-hour dark cycle. A dose of 1 ml of the test material was applied and spread once daily to the entire inner surface of once for five days per week for two weeks. The opposite untreated ear of each animal served as an untreated control.

The irritancy produced by repeated application of the chemical on the surface epidermis in the rabbit ear is evaluated on a scale of 0 to 5. The grades are summarized as follows:

 0 = No irritation; 1 = few scales, no Erythema; 2 = diffuse scaling, no Erythema; 3 = Generalized scaling with Erythema; 4 = Scaling, Erythema and Edema; 5 = Epidermal necrosis and slough.

The test chemical falls under Grade 0 (no irritation observed). Hence it can be concluded that the test chemical was not irritating to rabbit ears.

By applying the weight of evidence approach, the test chemical can be considered to be not irritating to skin. Comparing the annotations with criteria of CLP regulation, the test chemical can be classified under the category "Not Classified".

Eye Irritation

The eye irritation potential of the test chemical was assessed based on the available results from the various test chemicals.

An ocular irritation study was conducted on New Zealand white rabbits in accordance with OECD 405 to assess the irritation parameter of the test chemical. 3 female New Zealand White rabbits were used for the study. 0.1g of the undiluted test chemical was instilled in the conjunctival sac of rabbits after gently pulling the lower lid away from the eyeball. The other eye which remained untreated served as a control. The ocular lesions were evaluated at 1, 24, 48 and 72 hours after the treatment. The grades of ocular reactions (conjunctiva, cornea and iris) were recorded at each observation. To determine the reversibility of the effect the animals were observed normally for 21 days. Any other lesions in the eye viz pannus, staining were observed and scored accordingly. Examination of reactions was facilitated by use of biomicroscope and hand slit lamp. Individual animal weights before and during the study was observed.

The overall irritation index of the test chemical was 0.0 after 72 hours.

Also the test chemical did not produce any clinical signs of toxicity throughout the examination period of 21 days.

Hence, under the test conditions, the test chemical can be concluded to be not irritating to New Zealand White rabbit eyes.

This is supported by the results of a study performed to determine the local eye irritative potential of test chemical in rabbits’ eyes.

Rabbits received(number not specified) 2 installation 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 confirm the irritation potential. Hence, on the basis of findings the test chemical can be considered as not irritating to the rabbits’ eye.

By applying the weight of evidence approach, the test chemical can be considered to be not irritating to eyes. Comparing the annotations with criteria of CLP regulation, the test

chemical can be classified under the category "Not Classified".

Justification for classification or non-classification

The results of the experimental studies from the various test chemicals indicate a possibility thatthe test chemicalcan be not irritating to skin and eyes.

Hence, by applying the weight of evidence approach,the test chemicalcan be considered to be not irritating to skin and eyes. It can be classified under the category “Not Classified” as per CLP regulation.