Registration Dossier

Administrative data

Description of key information

Skin irritation

The dermal irritation potential of target chemical disodium [μ-[[7,7’-iminobis[4-hydroxy-3-[[2-hydroxy-5-sulphamoylphenyl]azo]naphthalene-2-sulphonato]](6-)]]dicuprate(2-) ; Direct Violet 66 (CAS No: 6798-03-4)  was assessedin various experimental studies which were conducted on rabbits and rats for target chemicaldisodium [μ-[[7,7’-iminobis[4-hydroxy-3-[[2-hydroxy-5-sulphamoylphenyl]azo]naphthalene-2-sulphonato]](6-)]]dicuprate(2-) ; Direct Violet 66 (CAS No: 6798-03-4)   and its structurally similar read across substanceTetra sodium 1-acetamido-2-hydroxy-3-(4-((4-sulphonatophenylazo)-7-sulphonato-1-naphthylazo))naphthalene-4,6-disulphonate[CAS:2519 -30 -4]andfunctionally similar read across substancealuminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex {CAS No: 15790-07-5}. The predicted data usingQSAR toolboxhas also been compared with the experimental data.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 disodium [μ-[[7,7’-iminobis[4-hydroxy-3-[[2-hydroxy-5-sulphamoylphenyl]azo]naphthalene-2-sulphonato]](6-)]]dicuprate(2-) ; Direct Violet 66 (CAS No: 6798-03-4)   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 disodium [μ-[[7,7’-iminobis[4-hydroxy-3-[[2-hydroxy-5-sulphamoylphenyl]azo]naphthalene-2-sulphonato]](6-)]]dicuprate(2-) ; Direct Violet 66 (CAS No: 6798-03-4)   was assessedin various experimental studies which were conducted on rabbits for target chemicaldisodium [μ-[[7,7’-iminobis[4-hydroxy-3-[[2-hydroxy-5-sulphamoylphenyl]azo]naphthalene-2-sulphonato]](6-)]]dicuprate(2-) ; Direct Violet 66 (CAS No: 6798-03-4)   and its structurally similar read across substance1,3 -Naphthalenedisulfonic acid, 7-hydroxy-8-((4-sulfo-1-naphthalenyl)azo)-, trisodium salt (Acid Red 18) [2611-82-7] andfunctionally similar read across substancesaluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (CAS No: 15790-07-5), Disodium 3-[(2,4-dimethyl-5-sulphonatophenyl)azo]-4-hydroxynaphthalene-1-sulphonate [CAS: 4548-53-2]. The predicted data usingQSAR toolboxhas also been compared with the experimental data.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 disodium [μ-[[7,7’-iminobis[4-hydroxy-3-[[2-hydroxy-5-sulphamoylphenyl]azo]naphthalene-2-sulphonato]](6-)]]dicuprate(2-) ; Direct Violet 66 (CAS No: 6798-03-4)   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:
(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 from OECD QSAR toolbox version 3.3 and QMRF report has been attached
Qualifier:
according to
Guideline:
other: estimated data
Principles of method if other than guideline:
Prediction is done using QSAR Toolbox version 3.3
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of the test material (IUPAC name): disodium [μ-[[7,7'-iminobis[4-hydroxy-3-[[2-hydroxy-5-sulphamoylphenyl]azo]naphthalene-2-sulphonato]](6-)]]dicuprate(2-)
- Molecular formula: C32H19Cu2N7Na2O14S4
- Molecular weight: 1026.87 g/mol
- Smiles: c1(S(=O)(=O)[O-])c(\N=N\c2cc(ccc2[O-])S(=O)(=O)N)c([O-])c2ccc(Nc3cc4cc(c(\N=N\c5c(ccc(c5)S(=O)(=O)N)[O-])c(c4cc3)[O-])S(=O)(=O)[O-])cc2c1.[Na+].[Na+].[Cu+2].[Cu+2]
- Inchl: 1S/C32H25N7O14S4.2Cu.2Na/c33-54(44,45)19-3-7-25(40)23(13-19)36-38-29-27(56(48,49)50)11-15-9-17(1-5-21(15)31(29)42)35-18-2-6-22-16(10-18)12-28(57(51,52)53)30(32(22)43)39-37-24-14-20(55(34,46)47)4-8-26(24)41;;;;/h1-14,35,40-43H,(H2,33,44,45)(H2,34,46,47)(H,48,49,50)(H,51,52,53);;;;/q;2*+2;2*+1/p-6/b38-36+,39-37+;;;;
- Substance type: Organic
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
No data available
Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
not specified
Controls:
not specified
Amount / concentration applied:
No data available
Duration of treatment / exposure:
24 hours
Observation period:
72 hours
Number of animals:
3
Details on study design:
No data available
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
72 h
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No skin irritation was observed in treated rabbits.

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

(((((((((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and "g" )  and ("h" and ( not "i") )  )  and ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and ("n" and ( not "o") )  )  and ("p" and ( not "q") )  )  and "r" )  and "s" )  and "t" )  and ("u" and "v" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Amine OR Anion OR Aromatic compound OR Azo compound OR Cation OR Secondary amine OR Secondary aromatic amine OR Sulfonamide OR Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aliphatic Nitrogen, one aromatic attach [-N] OR Aliphatic Nitrogen, two aromatic attach [-N-] OR Aromatic Carbon [C] OR Azo [-N=N-] OR Miscellaneous metal [Ni, Cu, Zr, Be] OR Miscellaneous sulfide (=S) or oxide (=O) OR Nitrogen, two or tree olefinic attach [>N-] OR Olefinic carbon [=CH- or =C<] OR Oxygen, one aromatic attach [-O-] OR Suflur {v+4} or {v+6} OR Sulfamide, aromatic attach [-SO2-N] OR Sulfonate, aromatic attach [-SO2-O] OR Sulfonyl amide, aromatic attach [-S(=O)N-] OR Sulfur, nitrogen attach [-S-] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aromatic amine OR Aryl OR Azo OR Fused carbocyclic aromatic OR Overlapping groups OR Phenol OR Sulfonamide OR Sulfonic acid by Organic Functional groups (nested) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aromatic amine OR Aryl OR Azo OR Fused carbocyclic aromatic OR Naphtalene OR Phenol OR Sulfonamide OR Sulfonic acid by Organic Functional groups ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr AND Group 11 - Trans.Metals Cu,Ag,Au AND Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O AND Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Group  3 - Lanthanoids OR Group 10 - Trans.Metals Ni,Pd,Pt OR Group 12 - Trans.Metals Zn,Cd,Hg OR Group 13 - Metalloids B OR Group 13 - Metals Al,Ga,In,Tl OR Group 14 - Metalloids Si,Ge OR Group 14 - Metals Sn,Pb OR Group 15 - Metalloids As,Sb OR Group 15 - Phosphorus P OR Group 17 - Halogens Br OR Group 17 - Halogens Cl OR Group 17 - Halogens F OR Group 17 - Halogens F,Cl,Br,I,At OR Group 17 - Halogens I OR Group 2 - Alkaline Earth Be,Mg,Ca,Sr,Ba,Ra OR Group 3 - Trans.Metals Sc,Y OR Group 4 - Trans.Metals Ti,Zr,Hf OR Group 5 - Trans.Metals V,Nb,Ta OR Group 6 - Trans.Metals Cr,Mo,W OR Group 7 - Trans.Metals Mn,Tc,Re OR Group 8 - Trans.Metals Fe,Ru,Os OR Group 9 - Trans.Metals Co,Rh,Ir by Chemical elements

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as 3-Methylcholantrene (Hepatotoxicity) Alert OR Aliphatic amines (Mucous membrane irritation) Rank C OR Aliphatic nitriles (Hepatotoxicity) Rank B OR Amineptine (Hepatotoxicity) Alert OR Aromatic hydrocarbons (Liver enzyme induction) Rank C OR Benzene/ Naphthalene sulfonic acids (Less susceptible) Rank C OR Benzenesulfonamides (Toxicity to urinary system) Rank B OR Chlorphentermine (Hepatotoxicity) Alert OR Oxyphenistain (Hepatotoxicity) Alert OR Tamoxifen (Hepatotoxicity) Alert OR Thiocarbamates/Sulfides (Hepatotoxicity) No rank by Repeated dose (HESS)

Domain logical expression index: "j"

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 Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "k"

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 C Surface Tension > 62 mN/m OR (!Undefined)Group CN Lipid Solubility < 0.4 g/kg OR (!Undefined)Group CNS Surface Tension > 62 mN/m by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "l"

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 Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Group All log Kow < -3.1 by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Ac-SN2 AND Ac-SN2 >> Acylation involving an activated (glucuronidated) sufonamide group AND Ac-SN2 >> Acylation involving an activated (glucuronidated) sufonamide group >> Arenesulphonamides AND AN2 AND AN2 >> Nucleophilic addition at polarized N-functional double bond AND AN2 >> Nucleophilic addition at polarized N-functional double bond >> Arenesulphonamides by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as AN2 >> Michael addition to the quinoid type structures OR AN2 >> Michael addition to the quinoid type structures >> N-Subsituted Aromatic Amines by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Aromatic Amine Type Compounds AND Arylazo Type Compounds by Oncologic Primary Classification

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Alkyl Sulfate and Alkyl Alkanesulfonate Type Compounds by Oncologic Primary Classification

Domain logical expression index: "r"

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

Domain logical expression index: "s"

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

Domain logical expression index: "t"

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

Domain logical expression index: "u"

Parametric boundary:The target chemical should have a value of log Kow which is >= -2.63

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of log Kow which is <= -0.608

Interpretation of results:
other: not irritating
Conclusions:
The chemical disodium [μ-[[7,7’-iminobis[4-hydroxy-3-[[2-hydroxy-5-sulphamoylphenyl]azo]naphthalene-2-sulphonato]](6-)]]dicuprate(2-) ; Direct Violet 66 (CAS No: 6798-03-4) was estimated to be not irritating to the skin of New Zealand White rabbits. Based on the estimated result disodium [μ-[[7,7’-iminobis[4-hydroxy-3-[[2-hydroxy-5-sulphamoylphenyl]azo]naphthalene-2-sulphonato]](6-)]]dicuprate(2-) ; Direct Violet 66 (CAS No: 6798-03-4) can be considered to be not irritating to skin.
Executive summary:

The dermal irritation potential of disodium [μ-[[7,7’-iminobis[4-hydroxy-3-[[2-hydroxy-5-sulphamoylphenyl]azo]naphthalene-2-sulphonato]](6-)]]dicuprate(2-) ; Direct Violet 66 (CAS No: 6798-03-4)  was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The chemical disodium [μ-[[7,7’-iminobis[4-hydroxy-3-[[2-hydroxy-5-sulphamoylphenyl]azo]naphthalene-2-sulphonato]](6-)]]dicuprate(2-) ; Direct Violet 66 (CAS No: 6798-03-4)   was estimated to be not irritating to the skin of New Zealand White rabbits. Based on the estimated result disodium [μ-[[7,7’-iminobis[4-hydroxy-3-[[2-hydroxy-5-sulphamoylphenyl]azo]naphthalene-2-sulphonato]](6-)]]dicuprate(2-) ; Direct Violet 66 (CAS No: 6798-03-4)   can be considered to be not irritating to skin and can be classified under the category ˋ Not Classified’ as per CLP regulation.

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

Eye irritation

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 chemicaldisodium [μ-[[7,7’-iminobis[4-hydroxy-3-[[2-hydroxy-5-sulphamoylphenyl]azo]naphthalene-2-sulphonato]](6-)]]dicuprate(2-) ; Direct Violet 66 (CAS No: 6798-03-4)    to observe the potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits and rats for target chemicaldisodium [μ-[[7,7’-iminobis[4-hydroxy-3-[[2-hydroxy-5-sulphamoylphenyl]azo]naphthalene-2-sulphonato]](6-)]]dicuprate(2-) ; Direct Violet 66 (CAS No: 6798-03-4)    and its structurally similar read across substancesTetra sodium 1-acetamido-2-hydroxy-3-(4-((4-sulphonatophenylazo)-7-sulphonato-1-naphthylazo))naphthalene-4,6-disulphonate[CAS:2519 -30 -4]andfunctionally similar read across substancealuminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex {CAS No: 15790-07-5} .The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

 

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 test chemicaldisodium [μ-[[7,7’-iminobis[4-hydroxy-3-[[2-hydroxy-5-sulphamoylphenyl]azo]naphthalene-2-sulphonato]](6-)]]dicuprate(2-) ; Direct Violet 66 (CAS No: 6798-03-4)  . The chemical disodium [μ-[[7,7’-iminobis[4-hydroxy-3-[[2-hydroxy-5-sulphamoylphenyl]azo]naphthalene-2-sulphonato]](6-)]]dicuprate(2-) ; Direct Violet 66 (CAS No: 6798-03-4)    is estimated to be not irritating to skin of New Zealand White rabbits.

 

A study was designed and conducted by Sustainability Support Services (Europe) AB, 2017 to determine the dermal reaction profile of read across substance Tetra sodium 1-acetamido-2-hydroxy-3-(4-((4-sulphonatophenylazo)-7-sulphonato-1-naphthylazo))naphthalene-4,6-disulphonate[CAS:2519 -30 -4] 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 test item Tetra sodium 1-acetamido-2-hydroxy-3-(4-((4-sulphonatophenylazo)-7-sulphonato-1-naphthylazo))naphthalene-4,6-disulphonate 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.  The overall irritation score of the substance was determined to be 0 and no erythema and edema (skin irritation) were found at the end of 14 days observation period after patch removal. Hence, it was concluded that Tetra sodium 1-acetamido-2-hydroxy-3-(4-((4-sulphonatophenylazo)-7-sulphonato-1-naphthylazo))naphthalene-4,6-disulphonate was Non-Irritating to the skin of Sprague Dawley rats under the experimental conditions tested.

 

The above results were further supported by another dermal irritation study conducted by Sustainability Support Services (Europe) AB, 2017 on three New Zealand white rabbits in accordance with OECD 404 to assess the irritation parameter of read across chemical aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex {CAS No: 15790-07-5} that supported the above mentioned results. 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) foraluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex {CAS No: 15790-07-5}after 14 days of observation was 0.0.Alsoaluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex {CAS No: 15790-07-5}Bdid not produce pain and any clinical signs of toxicity throughout the examination period of 14 days. Hence, under the test conditions, aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex {CAS No: 15790-07-5}can be concluded to be not irritating to New Zealand White rabbit skin.

 

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 disodium [μ-[[7,7’-iminobis[4-hydroxy-3-[[2-hydroxy-5-sulphamoylphenyl]azo]naphthalene-2-sulphonato]](6-)]]dicuprate(2-) ; Direct Violet 66 (CAS No: 6798-03-4)   is unable to cause skin 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”.

 

 

 

Eye irritation:

In different studies,the test chemicaldisodium [μ-[[7,7’-iminobis[4-hydroxy-3-[[2-hydroxy-5-sulphamoylphenyl]azo]naphthalene-2-sulphonato]](6-)]]dicuprate(2-) ; Direct Violet 66 (CAS No: 6798-03-4)    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 chemicaldisodium [μ-[[7,7’-iminobis[4-hydroxy-3-[[2-hydroxy-5-sulphamoylphenyl]azo]naphthalene-2-sulphonato]](6-)]]dicuprate(2-) ; Direct Violet 66 (CAS No: 6798-03-4)    andits structurally similar read across substance1,3 -Naphthalenedisulfonic acid, 7-hydroxy-8-((4-sulfo-1-naphthalenyl)azo)-, trisodium salt (Acid Red 18) [2611-82-7] andfunctionally similar read across substancesaluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (CAS No: 15790-07-5), Disodium 3-[(2,4-dimethyl-5-sulphonatophenyl)azo]-4-hydroxynaphthalene-1-sulphonate [CAS: 4548-53-2].The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

 

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the eye irritation potential was estimated for test chemicaldisodium [μ-[[7,7’-iminobis[4-hydroxy-3-[[2-hydroxy-5-sulphamoylphenyl]azo]naphthalene-2-sulphonato]](6-)]]dicuprate(2-) ; Direct Violet 66 (CAS No: 6798-03-4)  . The chemical disodium [μ-[[7,7’-iminobis[4-hydroxy-3-[[2-hydroxy-5-sulphamoylphenyl]azo]naphthalene-2-sulphonato]](6-)]]dicuprate(2-) ; Direct Violet 66 (CAS No: 6798-03-4)    is estimated to be not irritating to eye of New Zealand White rabbits.

 

An ocular irritation study was conducted by Sustainability Support Services (Europe) AB, 2017 on three New Zealand white rabbits in accordance with OECD 405 to assess the irritation parameter of read across chemical aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (CAS No: 15790-07-5). About 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 aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (CAS No: 15790-07-5) was 0.0 after 72 hours. Also aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (CAS No: 15790-07-5) did not produce any clinical signs of toxicity throughout the examination period of 21 days. Hence, under the test conditions, aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (CAS No: 15790-07-5)can be concluded  to be not irritating to New Zealand White rabbit eyes.

 

These results were supported by the experimental study summarized in 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 [CAS: 4548-53-2]. Ponceau SX 5% in formulation was instilled into the eyes of rabbits and observed for signs of irritation (duration not mentioned). Ponceau SX 5% in formulation did not cause any irritation to rabbit eyes. Hence, Ponceau SX can be considered not irritating to rabbit eyes.

 

The above results were further supported by the experimental study summarized in THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS (SCCNFP), last updated 23 April 2004; for the structurally similar read across substance, 1,3 -Naphthalenedisulfonic acid, 7-hydroxy-8-((4-sulfo-1-naphthalenyl)azo)-, trisodium salt (Acid Red 18) [2611-82-7]. The ocular irritation was assessed by determining the Cytotoxicity in the neutral red uptake assay (NRU) on human keratinocytes with the modification that human keratinocytes of the HaCaT cell line were used. The treatment was performed in serum-free culture medium. Doses from 681 – 10000 μg/ml [1% in water] were applied together with appropriate controls. Two independent NRU assays with identical doses were performed. No NRU-50 value could be determined from the cytotoxicity curves as the viability was still 61% in the first assay and 70% in the second, so the NRU-50 was reported to be > 10000 μg/ml. Hence, Acid red 18 can be considered not irritating to Human Keratinocytes in the neutral red uptake assay.

 

 

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 disodium [μ-[[7,7’-iminobis[4-hydroxy-3-[[2-hydroxy-5-sulphamoylphenyl]azo]naphthalene-2-sulphonato]](6-)]]dicuprate(2-) ; Direct Violet 66 (CAS No: 6798-03-4)   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 disodium [μ-[[7,7’-iminobis[4-hydroxy-3-[[2-hydroxy-5-sulphamoylphenyl]azo]naphthalene-2-sulphonato]](6-)]]dicuprate(2-) ; Direct Violet 66 (CAS No: 6798-03-4)    and its structurally and functionally similar read across substanceswere observed in various studies. The results obtained from these studies indicate that the chemical disodium [μ-[[7,7’-iminobis[4-hydroxy-3-[[2-hydroxy-5-sulphamoylphenyl]azo]naphthalene-2-sulphonato]](6-)]]dicuprate(2-) ; Direct Violet 66 (CAS No: 6798-03-4)   is unlikely to cause skin and eye irritation. Hence disodium [μ-[[7,7’-iminobis[4-hydroxy-3-[[2-hydroxy-5-sulphamoylphenyl]azo]naphthalene-2-sulphonato]](6-)]]dicuprate(2-) ; Direct Violet 66 (CAS No: 6798-03-4)    can be classified under the category “Not Classified” for skin and eye as per CLP.