Registration Dossier

Skin irritation :

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the skin irritation potential was estimated for Disodium 4-hydroxynaphthalene-2,7-disulphonate. It was estimated that Disodium 4-hydroxynaphthalene-2,7-disulphonatew as not irritating to skin of rabbits.

Eye irritation:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the ocular irritation potential was estimated for Disodium 4-hydroxynaphthalene-2,7-disulphonate. It was estimated that Disodium 4-hydroxynaphthalene-2,7-disulphonatew as not irritating to eye of rabbits.

Reference

Endpoint:

skin irritation: in vivo

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

Data is predicted using OECD QSAR toolbox version 3.4 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Prediction was done by using OECD QSAR toolbox v3.4,2017

GLP compliance:

not specified

Specific details on test material used for the study:

Name of test material: Disodium 4-hydroxynaphthalene-2,7-disulphonate
- Common name: 2,7-Naphthalenedisulfonic acid, 4-hydroxy-, sodium salt (1:2)
- Molecular formula: C10H6Na2O7S2
- Molecular weight: 348.2624 g/mol
- Smiles notation: c1cc2c(cc1S(=O)(=O)[O-])cc(cc2O)S(=O)(=O)[O-].[Na+].[Na+]
- InChl: 1S/C10H8O7S2.2Na/c11-10-5-8(19(15,16)17)4-6-3-7(18(12,13)14)1-2-9(6)10;;/h1-5,11H,(H,12,13,14)(H,15,16,17);;/q;2*+1/p-2
- Substance type: Organic

Species:

rabbit

Strain:

not specified

Details on test animals or test system and environmental conditions:

No data available

Type of coverage:

occlusive

Preparation of test site:

not specified

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

No data available

Duration of treatment / exposure:

No data available

Observation period:

No data available

Number of animals:

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 skin reaction

Estimation method: Takes mode value from the 5 nearest neighbours
Domain logical expression:Result: In Domain

((((((((("a" or "b" ) and ("c" and ( not "d") ) ) and ("e" and ( not "f") ) ) and "g" ) and "h" ) and ("i" and ( not "j") ) ) and "k" ) and "l" ) and ("m" and "n" ) )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Acid moiety AND Phenols AND Salt by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OECD

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Alkyl phenols OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated ketones OR SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Secondary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules (GSH) by Protein binding potency

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Moderately reactive (GSH) OR Moderately reactive (GSH) >> Alkyl 2-alkenoates (MA) by Protein binding potency

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as High (Class III) by Toxic hazard classification by Cramer (extension) ONLY

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Alkali Earth AND Non-Metals by Groups of elements

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Halogens by Groups of elements

Domain logical expression index: "k"

Similarity boundary:Target: Oc1cc(S(=O)(=O)O{-}.[Na]{+})cc2cc(S(=O)(=O)O{-}.[Na]{+})ccc12
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "l"

Similarity boundary:Target: Oc1cc(S(=O)(=O)O{-}.[Na]{+})cc2cc(S(=O)(=O)O{-}.[Na]{+})ccc12
Threshold=40%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is >= -4.13

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is <= -1.01

Interpretation of results:

not irritating

Conclusions:

Disodium 4-hydroxynaphthalene-2,7-disulphonate was considered to be non irritating to the skin of rabbit.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the skin irritation potential was estimated for Disodium 4-hydroxynaphthalene-2,7-disulphonate. It was estimated that Disodium 4-hydroxynaphthalene-2,7-disulphonatew as not irritating to skin of rabbits.

Endpoint conclusion:

no adverse effect observed (not irritating)

Reference

Endpoint:

eye irritation: in vivo

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

Data is predicted using OECD QSAR toolbox version 3.4 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Prediction was done by using OECD QSAR toolbox v3.4,2017

GLP compliance:

not specified

Specific details on test material used for the study:

Name of test material: Disodium 4-hydroxynaphthalene-2,7-disulphonate
- Common name: 2,7-Naphthalenedisulfonic acid, 4-hydroxy-, sodium salt (1:2)
- Molecular formula: C10H6Na2O7S2
- Molecular weight: 348.2624 g/mol
- Smiles notation: c1cc2c(cc1S(=O)(=O)[O-])cc(cc2O)S(=O)(=O)[O-].[Na+].[Na+]
- InChl: 1S/C10H8O7S2.2Na/c11-10-5-8(19(15,16)17)4-6-3-7(18(12,13)14)1-2-9(6)10;;/h1-5,11H,(H,12,13,14)(H,15,16,17);;/q;2*+1/p-2
- Substance type: Organic

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

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 ocular reaction

Estimation method: Takes mode value from the 5 nearest neighbours
Domain logical expression:Result: In Domain

((((((((("a" or "b" ) and ("c" and ( not "d") ) ) and ("e" and ( not "f") ) ) and "g" ) and "h" ) and "i" ) and "j" ) and ("k" and ( not "l") ) ) and ("m" and "n" ) )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Acid moiety AND Phenols AND Salt by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OECD

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Alkyl phenols OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated ketones OR SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Secondary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules (GSH) by Protein binding potency

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Moderately reactive (GSH) OR Moderately reactive (GSH) >> Alkyl 2-alkenoates (MA) by Protein binding potency

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as High (Class III) by Toxic hazard classification by Cramer (extension) ONLY

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Reactive unspecified by Acute aquatic toxicity MOA by OASIS ONLY

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Class 5 (Not possible to classify according to these rules) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as No alert found by Carcinogenicity (genotox and nongenotox) alerts by ISS

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Aromatic diazo (Genotox) OR Aromatic N-acyl amine (Genotox) OR Hydrazine (Genotox) OR Structural alert for genotoxic carcinogenicity by Carcinogenicity (genotox and nongenotox) alerts by ISS

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is >= -4.25

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is <= -2.43

Interpretation of results:

not irritating

Conclusions:

Disodium 4-hydroxynaphthalene-2,7-disulphonate was considered to be not eye irritant on rabbit eye.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the ocular irritation potential was estimated for Disodium 4-hydroxynaphthalene-2,7-disulphonate. It was estimated that Disodium 4-hydroxynaphthalene-2,7-disulphonatew as not irritating to eye of rabbits.

Endpoint conclusion:

no adverse effect observed (not irritating)

Endpoint conclusion:

no study available

Skin irritation :

In different studies, 2,7-Naphthalenedisulfonic acid, 4-hydroxy-, sodium salt (1:2) has been investigated for potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with human data for target chemical and its structurally similar read across substances Disodium 3-[(2,4-dimethyl-5-sulphonatophenyl)azo]-4-hydroxynaphthalene-1-sulphonate (4548-53-2) and Disodium 4-hydroxy-3-[(4-sulphonatonaphthyl)azo]naphthalene sulphonate (3567-96-9) .The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the skin irritation potential was estimated for Disodium 4-hydroxynaphthalene-2,7-disulphonate. It was estimated that Disodium 4-hydroxynaphthalene-2,7-disulphonatew as not irritating to skin of rabbits.

The above result was supported by experimental study conducted by Sustainability Support Services (Europe) AB, Sweden for its structurally similar read across substances Disodium 3-[(2,4-dimethyl-5-sulphonatophenyl)azo]-4-hydroxynaphthalene-1-sulphonate (4548-53-2) .

A study was designed and conducted to determine the dermal reaction profile of Disodium 3-[(2,4-dimethyl-5-sulphonatophenyl)azo]-4-hydroxynaphthalene-1-sulphonate 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 ‘Disodium 3-[(2,4-dimethyl-5-sulphonatophenyl)azo]-4-hydroxynaphthalene-1-sulphonate’ is non-irritant 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 substance, Disodium 3-[(2,4-dimethyl-5-sulphonatophenyl)azo]-4-hydroxy naphthalene-1-sulphonate can be classified under the category "Not Classified".

The above experimental study report was further supported by Sustainability Support Services (Europe) AB, Sweden for its structurally similar read across substances Disodium 4-hydroxy-3-[(4-sulphonatonaphthyl)azo]naphthalene sulphonate (3567-96-9).

A study was designed and conducted to determine the dermal reaction profile of Disodium 4-hydroxy-3-[(4-sulphonatonaphthyl)azo] naphthalenesulphonate 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 ‘Disodium 4-hydroxy-3-[(4-sulphonatonaphthyl)azo] naphthalenesulphonate’ 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 substance Disodium 4-hydroxy-3-[(4-sulphonatonaphthyl)azo] naphthalenesulphonate can be classified under the category "Not Classified".

Based on the available data for the target as well as it read across substances,it can be concluded that 2,7-Naphthalenedisulfonic acid, 4-hydroxy-, sodium salt (1:2) was not irritating to skin; and itcan be classified under the category “Not Classified” as per CLP regulation

Eye irritation:

In different studies, 2,7-Naphthalenedisulfonic acid, 4-hydroxy-, sodium salt (1:2) has been investigated for potential for ocular irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with human data for target chemical and its structurally similar read across substances Trisodium 5-hydroxy-1-(4-sulphophenyl)-4-(4-sulphophenylazo)pyrazole-3-carboxylate (1934-21-0) and Disodium 3-[(2,4-dimethyl-5-sulphonatophenyl)azo]-4-hydroxynaphthalene-1-sulphonate (4548-53-2) .The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the ocular irritation potential was estimated for Disodium 4-hydroxynaphthalene-2,7-disulphonate. It was estimated that Disodium 4-hydroxynaphthalene-2,7-disulphonatew as not irritating to eye of rabbits.

The above result was supported by experimental study conducted by Fd Chem. Toxic. Vol. 30, No. 12, pp. 1051-1055, 1992 for the structurally similar read across substance Trisodium 5-hydroxy-1-(4-sulphophenyl)-4-(4-sulphophenylazo)pyrazole-3-carboxylate (1934-21-0) .

Eye irritation test was conducted on 6 female and 6 male New Zealand White rabbits.30 μl of test chemical in aq. solution was administered into the right eye of rabbits and left eyes served as untreated controls.

Ocular irritation was determined according to a modification of the Draize test. All animals were checked for viability twice daily.Ocular irritation was scored 24 h after each treatment and prior to the next instillation. On days 1, 3, 7, 14, and 21 the eyes were also evaluated 1 h after treatment. 24 h after each treatment .

additionally eye stain and particle depositions were scored. Ophthalmic observations were conducted on days 3, 7 and 14 always prior to instillation.

No lethality or significant clinical signs, and no substance-related weight change were observed. Except slight conjunctival redness or discharge, that were seen sporadically in the eyes of the animals, all animals were free of significant signs of ocular irritation. No significant signs of eye staining or particle depositions were observed. At ophthalmoscopic examinations, no ocular abnormities were noticed.

Hence,tartrazine it is not expected to cause irritant effects following repeated treatment of eyes in a concentration of 3 % in aqueous solution.

Thus it can be concluded that Trisodium 5-hydroxy-1-(4-sulphophenyl)-4-(4-sulphophenylazo)pyrazole-3-carboxylate is not irritant to eye of rabbit.

The above study was further supported by experimental study conducted by Commission of the European Communities REPORTS of the Scientific Committee on Cosmetology (seventh series),1988 for the structurally similar read across substance Disodium 3-[(2,4-dimethyl-5-sulphonatophenyl)azo]-4-hydroxynaphthalene-1-sulphonate (4548-53-2) .

Disodium 3-[(2,4-dimethyl-5-sulphonatophenyl)azo]-4-hydroxynaphthalene-1-sulphonate when used as a test material for the evaluation of ocular irritation potential in 5% concentration, caused no ocular reaction on the rabbit eye, thus Disodium 3-[(2,4-dimethyl-5-sulphonatophenyl)azo]-4-hydroxynaphthalene-1-sulphonate is considered to be non irritating on the rabbit eye.

Based on the available data for the target as well as it read across substances,it can be concluded that 2,7-Naphthalenedisulfonic acid, 4-hydroxy-, sodium salt (1:2) was not irritating to eye; and itcan be classified under the category “Not Classified” as per CLP regulation.

Based on the available data for the target as well as it read across substances,it can be concluded that 2,7-Naphthalenedisulfonic acid, 4-hydroxy-, sodium salt (1:2) was not irritating to skin ans eye; and it can be classified under the category “Not Classified” as per CLP regulation.