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Description of key information

Skin irritation

The dermal irritation potential of target chemical Calcium 3-hydroxy-4-[(4-methyl-2-sulphonatophenyl)azo]-2-naphthoate/D&C Red 7/ Lithol rubine BK (CAS No: 5281-04-9) was assessedin various experimental studies which were conducted on rabbits and rats for target chemicalCalcium 3-hydroxy-4-[(4-methyl-2-sulphonatophenyl)azo]-2-naphthoate/D&C Red 7/ Lithol rubine BK (CAS No: 5281-04-9) and its structurally similar read across substances. Based on the available data for the target and read across substances, it can be concluded that chemical Calcium 3-hydroxy-4-[(4-methyl-2-sulphonatophenyl)azo]-2-naphthoate/D&C Red 7/ Lithol rubine BK (CAS No: 5281-04-9) is unable to cause skin irritation and thus considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

 

Eye irritation

An ocular irritation potential of target chemical Calcium 3-hydroxy-4-[(4-methyl-2-sulphonatophenyl)azo]-2-naphthoate/D&C Red 7/ Lithol rubine BK (CAS No: 5281-04-9) was assessedin various experimental studies which were conducted on rabbits for target chemicalCalcium 3-hydroxy-4-[(4-methyl-2-sulphonatophenyl)azo]-2-naphthoate/D&C Red 7/ Lithol rubine BK (CAS No: 5281-04-9) and its structurally similar read across substances. Based on the available data for the target and read across substances and applying the weight of evidence approach, it can be concluded that chemical Calcium 3-hydroxy-4-[(4-methyl-2-sulphonatophenyl)azo]-2-naphthoate/D&C Red 7/ Lithol rubine BK (CAS No: 5281-04-9) is unable to cause eye damage and thus can be considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it 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:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
data is from peer reviewed journals
Qualifier:
according to
Guideline:
other: as mentioned below
Principles of method if other than guideline:
The skin irritation study of test chemical D&C Red 7/ Lithol rubine BK (CAS No: 5281-04-9) was conducted on rabbits’ ear to indicate its Comedogenicity and irritancy.
GLP compliance:
not specified
Specific details on test material used for the study:
- IUPAC Name: calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate- Common Name: D & C Red no. 7- InChI:1S/C18H14N2O6S.Ca/c1-10-6-7-14(15(8-10)27(24,25)26)19-20-16-12-5-3-2-4-11(12)9-13(17(16)21)18(22)23;/h2-9,21H,1H3,(H,22,23)(H,24,25,26);/q;+2/p-2/b20-19+;- Smiles:c12c(c(c(C(=O)[O-])cc1cccc2)O)\N=N\c1c(cc(C)cc1)S(=O)(=O)[O-].[Ca+2]- Name of test material (as cited in study report):C. I. Pigment 57:1- Molecular formula :C18H12CaN2O6S- Molecular weight :424.445 g/mol- Substance type:organic- Physical state:solid
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALSSource: No dataAge at study initiation: No dataWeight at study initiation: 3 kg Fasting period before study: No dataHousing: singly housed, in suspended cagesDiet (e.g. ad libitum): Purina Rabbit Chow, ad libitumWater (e.g. ad libitum): water, ad libitumAcclimation period: No dataENVIRONMENTAL CONDITIONS Temperature (°C): No data Humidity (%):No data Air changes (per hr): No data Photoperiod (hrs dark / hrs light): 12 hour light and 12 hr dark cycleIN-LIFE DATES: From: No data To: No data
Type of coverage:
other: Entire inner surface of one ear
Preparation of test site:
other: A colony of rabbits that had genetically good ears and which were free from mites were used for the assay
Vehicle:
other: The test chemical was mixed in propylene glycol at a 9 to 1 dilution for testing.
Controls:
yes
Amount / concentration applied:
Dose of 1ml of the test material was applied once daily for five days per week for 2 weeks.
Duration of treatment / exposure:
once daily for five days per week for 2 weeks.
Observation period:
2 weeks
Number of animals:
3 rabbits
Details on study design:
TEST SITEArea of exposure: Ear% coverage: A dose of 1ml of the test chemical is applied and spread once daily to the entire inner surface of one ear five days per week for 2 weeks.Type of wrap if used: No dataREMOVAL OF TEST SUBSTANCEWashing (if done): No dataTime after start of exposure: No dataSCORING SYSTEM: The irritancy produced by repeated application of a chemical or skin care product 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 irritation1 = few scales, no Erythema2 = diffuse scaling, no Erythema3 = Generalized scaling with Erythema4 = Scaling, Erythema and Edema5 = Epidermal necrosis and slough
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 2 weeks
Score:
0
Max. score:
5
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No erythema observed
Interpretation of results:
other: not irritating
Conclusions:
The irritancy produced by D&C Red 7 was graded from 0 – 5. It falls under Grade 0 (no irritation observed).Hence it can be concluded that D&C Red 7/ Lithol rubine BK (CAS No: 5281-04-9) was not irritating to rabbits’ skin.
Executive summary:

The skin irritation study of test chemicalD&C Red 7/ Lithol rubine BK (CAS No:5281-04-9) was conducted onrabbits’ ear to indicate its Comedogenicity and irritancy.

 

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.

 

D&C Red 7 falls under Grade 0 (no irritation observed).

 

Hence it can be concluded that D&C Red 7/ Lithol rubine BK (CAS No:5281-04-9) was not irritating to rabbits’ skin

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:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
data from handbook or collection of data
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Principles of method if other than guideline:
An eye irritation study of test chemical D&C Red 7/ Lithol rubine BK (CAS No: 5281-04-9) was conducted on rabbits to observe its irritation efficacy in accordance with OECD guideline 405 .
GLP compliance:
not specified
Specific details on test material used for the study:
- IUPAC Name: calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate- Common Name: D & C Red no. 7- InChI:1S/C18H14N2O6S.Ca/c1-10-6-7-14(15(8-10)27(24,25)26)19-20-16-12-5-3-2-4-11(12)9-13(17(16)21)18(22)23;/h2-9,21H,1H3,(H,22,23)(H,24,25,26);/q;+2/p-2/b20-19+;- Smiles:c12c(c(c(C(=O)[O-])cc1cccc2)O)\N=N\c1c(cc(C)cc1)S(=O)(=O)[O-].[Ca+2]- Name of test material (as cited in study report):C. I. Pigment 57:1- Molecular formula :C18H12CaN2O6S- Molecular weight :424.445 g/mol- Substance type:organic- Physical state:solid
Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
No Data Available
Vehicle:
not specified
Controls:
not specified
Amount / concentration applied:
No Data Available
Duration of treatment / exposure:
No Data Available
Observation period (in vivo):
No Data Available
Duration of post- treatment incubation (in vitro):
No Data Available
Number of animals or in vitro replicates:
No Data Available
Details on study design:
No Data Available
Irritation parameter:
overall irritation score
Basis:
mean
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No eye irritation was observed in treated rabbits.
Interpretation of results:
other: Not irritating
Conclusions:
The test material D&C Red 7/ Lithol rubine BK (CAS No: 5281-04-9) was considered to be not irritating to the eyes of rabbits.
Executive summary:

An eye irritation study of test chemicalD&C Red 7/ Lithol rubine BK (CAS No:5281-04-9)was conducted on rabbits to observe its irritation efficacy in accordance with OECD guideline 405.

 

In this study, the test chemical was instilled into each rabbit’s eye and eye reactions were observed.

 

Since the test chemical did not cause irritation, thetest materialD&C Red 7/ Lithol rubine BK (CAS No:5281-04-9)was considered to be not irritating to rabbits’ eye.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

Various studieshas been investigated for the test chemical Calcium 3-hydroxy-4-[(4-methyl-2-sulphonatophenyl)azo]-2-naphthoate/D&C Red 7/ Lithol rubine BK (CAS No: 5281-04-9) to observe the potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbitsand humans for target chemicalD&C Red 7/ Lithol rubine BK (CAS No: 5281-04-9) and its structurally similar read across chemicals which have beensummarized as below;

 

The skin irritation study of test chemical D&C Red 7/ Lithol rubine BK (CAS No: 5281-04-9) was conducted by peer reviewed journal on rabbits’ ear to indicate its Comedogenicity and irritancy. 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. D&C Red 7 falls under Grade 0 (no irritation observed). Hence it can be concluded that D&C Red 7/ Lithol rubine BK (CAS No: 5281-04-9) was not irritating to rabbits’ skin.

 

The next skin irritation study of test chemicalD&C Red 7/ Lithol rubine BK (CAS No:5281-04-9)was conducted by authoritative database on rabbits to observe its irritation efficacy in accordance with OECD guideline 404.In this study, the test chemical was applied dermally on to each rabbit’s skin and eye reactions were observed.Since the test chemical did not cause irritation, thetest materialD&C Red 7/ Lithol rubine BK (CAS No:5281-04-9)was considered to be not irritating to rabbits’ skin.

 

A Draize Test of test chemicalD&C Red 7/ Lithol rubine BK (CAS No:5281-04-9)was reported by safety assessment report on ear of three rabbits to assess skin irritation potential. About 10% solution of lithol rubine BK in propylene glycol was applied on to the ear of each rabbits 5 days/week for 2 weeks under non-occlusive condition. After observation it was concluded that the chemical did not cause skin irritating effects and therefore the test chemicalD&C Red 7/ Lithol rubine BK (CAS No:5281-04-9)was considered to be not irritating to the skin of rabbits.

 

Another skin irritation study of test chemicalD&C Red 7/ Lithol rubine BK (CAS No:5281-04-9)was reported by same safety assessment report according to OECD Guide–line 404 "Acute Dermal Irritation/Corrosion".When the chemical was administrated on to the skin of each rabbit, none of the treated rabbits had developed any signs of skin irritating effects.Hence the test thetest materialD&C Red 7/ Lithol rubine BK (CAS No:5281-04-9)was considered to be not irritating to the rabbits’ skin.

 

Another dermal irritation study of test chemical was reported by safety assessment report andOECD SIDS on rabbits. during the test,there was no evidence of skin lesions occurred in treated rabbits, when exposed to the test chemical.Hence the test thetest materialD&C Red 7/ Lithol rubine BK (CAS No:5281-04-9)was considered to be not irritating to the rabbits’ skin.

 

InOECD SIDS, next skin irritation study of test chemicalD&C Red 7/ Lithol rubine BK (CAS No:5281-04-9)was conducted on rabbits. The rabbits were exposed to the test chemical dermally and then skin reactions were scored.The average score for redness or swelling was estimated to be 0.5 (maximum primary skin irritation score=8°).Hence the test thetest materialD&C Red 7/ Lithol rubine BK (CAS No:5281-04-9)was considered to be not irritating to the rabbits’ skin.

 

The authoritative database conducted apatch study of test chemical D&C Red 7/ Lithol rubine BK (CAS No:5281-04-9)on ten women to assess its adverse effects A formulation of 50% LRBK in was applied to the skin of 10 female in a continuous occlusive patch test over 21 days which induced only minimal irritative effects. Hence thetest materialD&C Red 7/ Lithol rubine BK (CAS No:5281-04-9)was considered to be slightly irritating.

 

The above results were further supported by an experimental dermal study conducted for read across chemical in Sprague Dawley rats. The study was performed as per OECD Guidelines 402 and complying to the GLP procedures. The test item 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. 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.From the study, it can be concluded that the test substance is nonirritant to the skin of Sprague Dawley rats when applied to the shorn skin of 5 male and 5 female animals at the tested dose level of 2000 mg/kg body weight. Also the erythema and edema score of rats was calculated as 0. Thus it can be concluded that the test substance was non-Irritating to the skin of rats under the experimental conditions tested.

 

 

The overall results were further supported by the experimental study conducted by peer reviewed journal for read across substance on rabbits’ ear . 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 chemical falls under Grade 0 (no irritation observed). Hence it can be concluded that the test chemical was not irritating to rabbits’ skin.

 

Even though one study states that the chemical caused slight skin irritation but the potential of causing irritation was low. As per these findings, the chemical cannot be classified. Also on the basis of available dataand majority of results obtained in various studies, the test chemical Calcium 3-hydroxy-4-[(4-methyl-2-sulphonatophenyl)azo]-2-naphthoate/D&C Red 7/ Lithol rubine BK (CAS No: 5281-04-9) can beconsidered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

 

Eye irritation:

In different studies,the test chemical Calcium 3-hydroxy-4-[(4-methyl-2-sulphonatophenyl)azo]-2-naphthoate/D&C Red 7/ Lithol rubine BK (CAS No: 5281-04-9)has been investigated for potential for ocular irritationto a greater or lesser extent. The studies are based on in vivo experiments in rabbits for target chemical Calcium 3-hydroxy-4-[(4-methyl-2-sulphonatophenyl)azo]-2-naphthoate/D&C Red 7/ Lithol rubine BK (CAS No: 5281-04-9) and its structurally similar read across substancesthat have beensummarized as below;

 

An eye irritation study of test chemicalD&C Red 7/ Lithol rubine BK (CAS No:5281-04-9)was conducted by an authoritative database on rabbits to observe its irritation efficacy in accordance with OECD guideline 405.In this study, the test chemical was instilled into each rabbit’s eye and eye reactions were observed.Since the test chemical did not cause irritation, thetest materialD&C Red 7/ Lithol rubine BK (CAS No:5281-04-9)was considered to be not irritating to rabbits’ eye.

 

The next ocular irritation study of test chemicalD&C Red 7/ Lithol rubine BK (CAS No:5281-04-9)was reported by safety assessment report on rabbits according to OECD Guide–line 405 "Acute Eye Irritation/Corrosion".When the chemical was administrated into the eyes of each rabbit, none of the treated rabbits had developed any signs of eye irritating effects.Hence the test thetest materialD&C Red 7/ Lithol rubine BK (CAS No:5281-04-9)was considered to be not irritating to the rabbits’ eye.

 

Another eye irritation study of test chemical D&C Red 7/ Lithol rubine BK (CAS No: 5281-04-9) was reported by the above mentioned safety assessment report on rabbits to observe its eye irritation efficacy. During the study, there was no evidence of ocular lesions occurred in treated rabbits, when the test instilled into the eyes of each rabbits. Hence the test material D&C Red 7/ Lithol rubine BK (CAS No: 5281-04-9) was considered to be not irritating to the rabbits’ eye.

 

The OECD SIDS summarized an eye irritation study of test chemical D&C Red 7/ Lithol rubine BK (CAS No: 5281-04-9). The chemical did not cause ulceration, corneal opacity or iris inflammation, or slight redness or swelling, when the test instilled into the eyes of each rabbits. Hence the test material D&C Red 7/ Lithol rubine BK (CAS No: 5281-04-9) was considered to be not irritating to the rabbits’ eye.

 

Another ocular study was assessed by authoritative database for the test compound D&C Red 7/ Lithol rubine BK (CAS No: 5281-04-9) in rabbits. About 0.2 ml 10% aqueous solution of C.I. Pigment Red 57:1 was instilled 2 times a day, 5 times per week for 4 weeks in the conjunctival sac of rabbits and observed for signs of irritation. Repeated exposure of C.I. Pigment Red 57:1 to rabbit eyes caused only temporary irritation which did not persist till the end of the study. Hence, C.I. Pigment Red 57:1 can be considered not irritating to rabbit eyes.

 

The above results were further supported by an ocular irritation study was conducted on New Zealand white rabbits in accordance with OECD 405 to assess the irritation parameter of test chemical 3 female New Zealand White rabbits were used for the study. In this 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 test chemical was 0.0 after 72 hours. Also test chemical did not produce any clinical signs of toxicity throughout the examination period of 21 days. Hence, under the test conditions, test chemical can be concluded to be not irritating to New Zealand White rabbit eyes.

 

The overall results were further supported by the local eye irritation study of test chemical. Each rabbit received 2 installation of 0.2 ml of a 10% of test chemical aqueous suspension into the conjunctival sac of rabbits 5 times per week for 4 weeks. The chemical produced only minimal irritating 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.

 

 Based on the available data for thetarget chemicalCalcium 3-hydroxy-4-[(4-methyl-2-sulphonatophenyl)azo]-2-naphthoate/D&C Red 7/ Lithol rubine BK (CAS No: 5281-04-9) and its structurally similar read across substances,it can be concluded thatchemical Calcium 3-hydroxy-4-[(4-methyl-2-sulphonatophenyl)azo]-2-naphthoate/D&C Red 7/ Lithol rubine BK (CAS No: 5281-04-9) is unable to cause eye irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

 

Justification for classification or non-classification

The skin and eye irritation potential of test chemical Calcium 3-hydroxy-4-[(4-methyl-2-sulphonatophenyl)azo]-2-naphthoate/D&C Red 7/ Lithol rubine BK (CAS No: 5281-04-9) were observed in various studies. The results obtained from these studies indicate that the chemical is unlikely to cause skin and eye irritation. Hence Calcium 3-hydroxy-4-[(4-methyl-2-sulphonatophenyl)azo]-2-naphthoate/D&C Red 7/ Lithol rubine BK (CAS No: 5281-04-9) can be classified under the category “Not Classified” for skin and eye as per CLP.