Disodium 5-amino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate

Endpoint summary

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:

key study

Reliability:

2 (reliable with restrictions)

Principles of method if other than guideline:

The test uses a single rabbit ear, to indicate the Comedogenicity and irritancy of group of skin care products that may contain follicular and surface epithelial irritating ingredients.

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALSSource: Age at study initiation:Weight at study initiation: 3 kg Fasting period before study:Housing: singly housed, in suspended cagesDiet (e.g. ad libitum): Purina Rabbit Chow, ad libitumWater (e.g. ad libitum): water, ad libitumAcclimation period:ENVIRONMENTAL CONDITIONS Temperature (°C): Humidity (%): Air changes (per hr): Photoperiod (hrs dark / hrs light): 12 hour light and 12 hr dark cycle

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:

other: Other ear acted as control.

Amount / concentration applied:

Dose of 1ml of the test material

Duration of treatment / exposure:

The test material was applied once daily for five days per week for 2 weeks.

Observation period:

No data

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:REMOVAL OF TEST SUBSTANCEWashing (if done):Time after start of exposure:SCORING 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:

other:

Time point:

other: 2 weeks

Score:

2

Max. score:

5

Reversibility:

no data

Interpretation of results:

not irritating

Remarks:

Migrated informationCriteria used for interpretation of results: EU

Conclusions:

The test uses a single rabbit ear, to indicate the Comedogenicity and irritancy of group of skin care products that may contain follicular and surface epithelial irritating ingredients . The irritancy produced by the test chemical was graded from 0 – 5. The test chemical falls under Grade 2 (diffuse scaling, no erythema) Hence it can be concluded that the test chemical is non-irritating to rabbit ears.

Executive summary:

The test uses a single rabbit ear, to indicate the Comedogenicity and irritancy of group of skin care products that may contain follicular and surface epithelial irritating ingredients. Ingredients are 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 is free from mites is used. Three rabbits, weighing two to three kilograms, are used for each assay. Animals are housed singly in suspended cages and fed Purina Rabbit Chow and water ad libitum. Animals are maintained on a 12-hourlight and 12-hour dark cycle. A dose of 1 ml of the test material is 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 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 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 2 (diffuse scaling, no erythema)

Hence it can be concluded that the test chemical is non-irritating to rabbit ears. Based on the above result the test chemical D&C Red 33 not classified as skin irritent.

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:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3 .

GLP compliance:

no

Species:

rabbit

Strain:

not specified

Vehicle:

not specified

Controls:

yes

Amount / concentration applied:

0.1 mL

Observation period (in vivo):

24, 48, and 72 hours

Number of animals or in vitro replicates:

3

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 72 h

Reversibility:

not specified

Remarks on result:

other: not irritating

Estimation method: Takes mode value from the 7 nearest neighbours
Domain  logical expression:Result: In Domain

((("a" or "b" or "c" or "d" or "e" )  and ("f" and ( not "g") )  )  and ("h" and "i" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Anilines (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aniline AND Aryl AND Azo AND Fused carbocyclic aromatic AND Naphtalene AND Phenol AND Sulfonic acid by Organic Functional groups

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aniline AND Aryl AND Azo AND Fused carbocyclic aromatic AND Naphtalene AND Overlapping groups AND Phenol AND Sulfonic acid by Organic Functional groups (nested)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] AND Aliphatic Nitrogen, one aromatic attach [-N] AND Aromatic Carbon [C] AND Azo [-N=N-] AND Hydroxy, aromatic attach [-OH] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] AND Suflur {v+4} or {v+6} AND Sulfonate, aromatic attach [-SO2-O] by Organic functional groups (US EPA)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Amine AND Anion AND Aromatic compound AND Azo compound AND Cation AND Hydroxy compound AND Phenol AND Primary amine AND Primary aromatic amine AND Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND Group All Melting Point > 200 C by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as (!Undefined)Group All log Kow < -3.1 OR (!Undefined)Group All log Kow > 9 OR (!Undefined)Group All Melting Point > 200 C OR (!Undefined)Group CN Lipid Solubility < 0.4 g/kg OR (!Undefined)Group CNHal Lipid Solubility < 400 g/kg OR Exclusion rules not met OR Group All Aqueous Solubility < 0.000005 g/L OR Group All Aqueous Solubility < 0.00002 g/L OR Group All log Kow < -3.1 OR Group All log Kow > 9 OR Group All Molecular Weight > 650 g/mol OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN Molecular Weight > 290 g/mol OR Group CNHal Aqueous Solubility < 0.004 g/L OR Group CNHal Aqueous Solubility < 0.1 g/L OR Group CNHal log Kow > 3.8 OR Group CNHal Molecular Weight > 370 g/mol OR Group CNS Aqueous Solubility < 0.006 g/l OR Group CNS log Kow < -2 OR Group CNS log Kow > 1.5 OR Group CNS log Kow > 3.6 OR Group CNS Melting Point > 200 C OR Group CNS Melting Point > 50 C OR Group CNS Molecular Weight > 620 g/mol by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "h"

Parametric boundary:The target chemical should have a value of log Kow which is >= -2.61

Domain logical expression index: "i"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.303

Interpretation of results:

not classified

Remarks:

Migrated informationCriteria used for interpretation of results: EU

Conclusions:

The substance D&C Red No. 33 is estimated to be not irritating to albino rabbits eye .

Executive summary:

The eye irritating potential of D&C Red No. 33 is predicted using OECD QSAR toolbox version 3.3. The substance D&C Red No. 33 is estimated to be not irritating to albino rabbits eye .

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

 Skin irritation / corrosion

In a Primary Skin Irritation Test for D&C Red 33 reported in JAMES E. FULTON, 1989, the test uses a single rabbit ear, to indicate the Comedogenicity and irritancy of group of skin care products that may contain follicular and surface epithelial irritating ingredients. Ingredients are mixed in propylene glycol at a 9 to 1 dilution for testing unless otherwise indicated (10% concentration).Three rabbits, weighing two to three kilograms, are used for each assay.A dose of 1 ml of the test material is 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 the test chemical was graded from 0–5. The test chemical falls under Grade 2 (diffuse scaling, no erythema). Hence it can be concluded that the test chemical is non-irritating to rabbit ears.

In a Primary Skin Irritation Test reported in Scientific Committee on Consumer Safety (2007),Test substance Acid Red 33 of dose concentration 0.5 g/kg bw of a 0, 0.1 and 1% formulation in white petrolatum or a hydrophilic cream was applied on intact skin of rabbits for 65 applications or on damaged skin for 15 applications. Under the conditions of the study, the test material was considered not be irritant to rabbit skin.

In another study (J.H. Draize; et.al-1944,Dipali Roy & J. Saha -1981 and European Commission-2011) with similar substance (CAS: 633-96-5),100 mg of the test material were applied on the abraded skin of 4 male rabbit for 24 hour.Test material produced very slight redness of abraded skin in some of the rabbits when observed at only 24 hours after application. The overall result concluded that this was a false positive reaction. Under the conditions in this experiment the material Acid Orange 7 is classified as non-irritant to the skin.

On the basis of available information for the target as well as read across substance and applying weight of evidence approach, the test substance can be considered as not irritating to the skin, in accordance with the CLP criteria.

Eye irritation:

Applying weight of evidence approach to the available predicted and experimental data for the target as well as read-across chemical, the information is summarised as below.

The eye irritating potential of D&C Red No. 33 is predicted using OECD QSAR toolbox version 3.3. The substance D&C Red No. 33 is estimated to be not irritating to albino rabbits eye .

In a Primary Eye Irritation Test reported in Scientific Committee on Consumer Safety 2007,0.2 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 study concluded that the test substance was not irritating to the rabbit eye.

In a study (Dipali Roy & J. Saha- 1981 and European Commission 2011) conducted on similar substance (CAS: 633-96-5);100 mg of test compound (Acid Orange 7)was administered to eye of 3 male rabbits no sign of irritation was observed during experiment thus it is concluded that Acid Orange 7 dose not classify as eye irritant.

On the basis of available information for the target as well as read across substance and applying weight of evidence approach, the test substance can be considered as not irritating to the eye, in accordance with the CLP criteria.

Justification for selection of skin irritation / corrosion endpoint:
In a Primary Skin Irritation Test for D&C Red 33 reported in JAMES E. FULTON, 1989, the test uses a single rabbit ear, to indicate the Comedogenicity and irritancy of group of skin care products that may contain follicular and surface epithelial irritating ingredients. Ingredients are mixed in propylene glycol at a 9 to 1 dilution for testing unless otherwise indicated (10% concentration).Three rabbits, weighing two to three kilograms, are used for each assay.A dose of 1 ml of the test material is 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 the test chemical was graded from 0–5. The test chemical falls under Grade 2 (diffuse scaling, no erythema). Hence it can be concluded that the test chemical is non-irritating to rabbit ears.

Justification for selection of eye irritation endpoint:
The eye irritating potential of D&C Red No. 33 is predicted using OECD QSAR toolbox version 3.3. The substance D&C Red No. 33 is estimated to be not irritating to albino rabbits eye .

Justification for classification or non-classification

On the basis of the available data, the substance can be considered to be not irritating to skin and eyes.

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