Trisodium 4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato-2-naphthyl]amino]carbonyl]amino]-3-sulphonato-2-naphthyl]azo]benzoate

Endpoint summary

Description of key information

Acute Oral Toxicity:

The LD50 was estimated to be 4438.20 mg/kg bw,when TIf: RAI f (SPF) male and female rats were orally exposed with Trisodium 4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato-2-naphthyl]amino]carbonyl]amino]-3-sulphonato-2-naphthyl]azo]benzoate (6598-63-6) via gavage.

Acute Dermal Toxicity:

The LD50 value was estimated to be 10239.41 mg/kg bw, when male and female Vienna White rabbits were exposed semiocclusively with Trisodium 4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato-2-naphthyl]amino]carbonyl]amino]-3-sulphonato-2-naphthyl]azo]benzoate (6598-63-6) by dermal application for 24 hours.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

calculation (if not (Q)SAR)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Justification for type of information:

Data is from Danish QSAR

Qualifier:

equivalent or similar to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Prediction is done by using Danish QSAR database

GLP compliance:

not specified

Test type:

other: Not specified

Limit test:

no

Specific details on test material used for the study:

- Name of test material (IUPAC name): Trisodium 4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato-2-naphthyl]amino]carbonyl]amino]-3-sulphonato-2-naphthyl]azo]benzoate
- Common name: trisodium 4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato-2-naphthyl]amino]carbonyl]amino]-3-sulphonato-2-naphthyl]azo]benzoate
- Molecular formula: C34H21N6Na3O11S2
- Molecular weight: 822.673 g/mol
- Smiles notation: c12c(cc(c(c2S(=O)(=O)[O-])\N=N\c2ccc(cc2)C(=O)[O-])O)cc(NC(=O)Nc2cc3cc(S(=O)(=O)[O-])c(\N=N\c4ccccc4)c(c3cc2)O)cc1.[Na+].[Na+].[Na+]
-InChl:1S/C34H24N6O11S2.3Na/c41-27-16-19-14-24(11-13-26(19)32(53(49,50)51)29(27)39-38-22-8-6-18(7-9-22)33(43)44)36-34(45)35-23-10-12-25-20(15-23)17-28(52(46,47)48)30(31(25)42)40-37-21-4-2-1-3-5-21;;;/h1-17,41-42H,(H,43,44)(H2,35,36,45)(H,46,47,48)(H,49,50,51);;;/q;3*+1/p-3/b39-38+,40-37+;;;
- Substance type: Organic

Species:

mouse

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

No data available

Route of administration:

oral: unspecified

Vehicle:

not specified

Details on oral exposure:

No data available

Doses:

7600 mg/kg bw

No. of animals per sex per dose:

No data available

Control animals:

not specified

Details on study design:

No data available

Statistics:

No data available

Preliminary study:

No data available

Sex:

not specified

Dose descriptor:

LD50

Effect level:

7 600 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality was observed

Mortality:

No data available

Clinical signs:

other: No data available

Gross pathology:

No data available

Other findings:

No data available

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

Based on the QSAR prediction done using the Danish (Q)SAR Database, the LD50 was estimated to be 7600 mg/kg bw on mouse for test substance Trisodium 4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato-2-naphthyl]amino]carbonyl]amino]-3-sulphonato-2-naphthyl]azo]benzoate (6598-63-6) orally.

Executive summary:

Based on the QSAR prediction done using the Danish (Q)SAR Database, the LD50 was estimated to be 7600 mg/kg bw on mouse for Trisodium 4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato-2-naphthyl]amino]carbonyl]amino]-3-sulphonato-2-naphthyl]azo]benzoate (6598-63-6)having Reliability Index: 0.55(moderate prediction quality).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

4 438.2 mg/kg bw

Quality of whole database:

Data is Klimicsh 2 and from QSAR Toolbox 3.3 (2017)

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

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 3.3 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 v3.3,2017

GLP compliance:

not specified

Test type:

other: Estimated data

Limit test:

no

Specific details on test material used for the study:

- Name of test material (IUPAC name): Trisodium 4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato-2-naphthyl]amino]carbonyl]amino]-3-sulphonato-2-naphthyl]azo]benzoate
- Common name: trisodium 4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato-2-naphthyl]amino]carbonyl]amino]-3-sulphonato-2-naphthyl]azo]benzoate
- Molecular formula: C34H21N6Na3O11S2
- Molecular weight: 822.673 g/mol
- Smiles notation: c12c(cc(c(c2S(=O)(=O)[O-])\N=N\c2ccc(cc2)C(=O)[O-])O)cc(NC(=O)Nc2cc3cc(S(=O)(=O)[O-])c(\N=N\c4ccccc4)c(c3cc2)O)cc1.[Na+].[Na+].[Na+]
-InChl:1S/C34H24N6O11S2.3Na/c41-27-16-19-14-24(11-13-26(19)32(53(49,50)51)29(27)39-38-22-8-6-18(7-9-22)33(43)44)36-34(45)35-23-10-12-25-20(15-23)17-28(52(46,47)48)30(31(25)42)40-37-21-4-2-1-3-5-21;;;/h1-17,41-42H,(H,43,44)(H2,35,36,45)(H,46,47,48)(H,49,50,51);;;/q;3*+1/p-3/b39-38+,40-37+;;;
- Substance type: Organic

Species:

rabbit

Strain:

Vienna White

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data available

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

No data available

Duration of exposure:

24 hours

Doses:

10239.41 mg/kg bw

No. of animals per sex per dose:

No data available

Control animals:

not specified

Details on study design:

No data available

Statistics:

No data available

Preliminary study:

No data available

Sex:

male/female

Dose descriptor:

LD50

Effect level:

10 239.41 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% Mortality was observed

Mortality:

No data available

Clinical signs:

other: No data available

Gross pathology:

No data available

Other findings:

No data available

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as SN1 OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic phenylureas by DNA binding by OECD ONLY

Domain logical expression index: "b"

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

Domain logical expression index: "c"

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

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] OR Aliphatic Nitrogen, one aromatic attach [-N] OR Aromatic Carbon [C] OR Azo [-N=N-] OR Carbonyl, olefinic attach [-C(=O)-] OR Carbonyl, one aromatic attach [-C(=O)-] OR Hydroxy, aromatic attach [-OH] 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 Sulfonate, aromatic attach [-SO2-O] OR Urea [-OC(=O)N-] OR Urea, N and N'-diaryl subsrituted  by Organic functional groups (US EPA) ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] OR Aliphatic Nitrogen, one aromatic attach [-N] OR Aromatic Carbon [C] OR Azo [-N=N-] OR Carbonyl, olefinic attach [-C(=O)-] OR Carbonyl, one aromatic attach [-C(=O)-] OR Hydroxy, aromatic attach [-OH] 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 Sulfonate, aromatic attach [-SO2-O] OR Urea [-OC(=O)N-] OR Urea, N and N'-diaryl subsrituted  by Organic functional groups (US EPA) ONLY

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Anion OR Aromatic compound OR Azo compound OR Carbonic acid derivative OR Carboxylic acid derivative OR Carboxylic acid salt OR Cation OR CO2 derivative (general) OR Hydroxy compound OR Phenol OR Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds >> alpha, beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> alpha, beta-Unsaturated Aldehydes OR Michael addition OR Michael addition >> Quinone type compounds OR Michael addition >> Quinone type compounds >> Quinone methides OR Radical OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA >> Organic Peroxy Compounds OR Radical >> ROS formation after GSH depletion OR Radical >> ROS formation after GSH depletion >> Quinone methides OR SN1 OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN2 OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon Derivatives by DNA binding by OASIS v.1.3

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Alkaline Earth OR Halogens OR Metalloids OR Metals OR Rare Earth OR Transition Metals by Groups of elements

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr 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: "m"

Referential boundary: The target chemical should be classified as Group 15 - Phosphorus P by Chemical elements

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as 3-Methylcholantrene (Hepatotoxicity) Alert OR Acrylamides (Neurotoxicity) 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 Oxyphenistain (Hepatotoxicity) Alert OR Tamoxifen (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for skin sensitization by OASIS v1.3

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Michael Addition OR Michael Addition >> Polarised Alkenes OR Michael Addition >> Polarised Alkenes >> Polarised Alkene - alkenyl pyridines, pyrazines, pyrimidines or triazines  OR Michael Addition >> Polarised Azo compounds OR Michael Addition >> Polarised Azo compounds >> Azocarbonamides OR SN2 OR SN2 >> Interchange reaction with sulphur containing compounds OR SN2 >> Interchange reaction with sulphur containing compounds >> Thiols and disulfide compounds  by Protein binding alerts for skin sensitization by OASIS v1.3

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as H-acceptor-path3-H-acceptor by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as alpha,beta-unsaturated aliphatic alkoxy group OR No alert found by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as No alert found by in vitro mutagenicity (Ames test) alerts by ISS

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Alkyl hydroperoxides by in vitro mutagenicity (Ames test) alerts by ISS

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Very fast by Bioaccumulation - metabolism half-lives ONLY

Domain logical expression index: "w"

Parametric boundary:The target chemical should have a value of log Kow which is >= -6.2

Domain logical expression index: "x"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.14

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The LD50 value was estimated to be 10239.41 mg/kg bw, when male and female Vienna White rabbits were exposed semiocclusively with Trisodium 4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato-2-naphthyl]amino]carbonyl]amino]-3-sulphonato-2-naphthyl]azo]benzoate (6598-63-6) by dermal application for 24 hours.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for Trisodium 4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato-2-naphthyl]amino]carbonyl]amino]-3-sulphonato-2-naphthyl]azo]benzoate (6598-63-6).The LD50 was estimated to be 10239.41mg/kg bw,when male and female Vienna White rabbits were exposed semiocclusively with Trisodium 4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato-2-naphthyl]amino]carbonyl]amino]-3-sulphonato-2-naphthyl]azo]benzoate (6598-63-6)by dermal application for 24 hours.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

10 239.41 mg/kg bw

Quality of whole database:

Data is Klimicsh 2 and from QSAR Toolbox 3.3. (2017)

Additional information

Acute Oral Toxicity:

In different studies, Trisodium 4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato-2-naphthyl]amino]carbonyl]amino]-3-sulphonato-2-naphthyl]azo]benzoate (6598-63-6) has been investigated for acute oral toxicity to a greater or lesser extent. Often the studies are based on in vivo experiments and estimated data in rodents, i.e. most commonly in rats for Trisodium 4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato-2-naphthyl]amino]carbonyl]amino]-3-sulphonato-2-naphthyl]azo]benzoate (6598-63-6).The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for Trisodium 4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato-2-naphthyl]amino]carbonyl]amino]-3-sulphonato-2-naphthyl]azo]benzoate (6598-63-6).The LD50 was estimated to be 4438.20 mg/kg bw,when TIf: RAI f (SPF) male and female rats were orally exposed with Trisodium 4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato-2-naphthyl]amino]carbonyl]amino]-3-sulphonato-2-naphthyl]azo]benzoate (6598-63-6) via gavage.

Based on the QSAR prediction done using the Danish (Q)SAR Database, the LD50 was estimated to be 7600 mg/kg bw on mouse for Trisodium 4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato-2-naphthyl]amino]carbonyl]amino]-3-sulphonato-2-naphthyl]azo]benzoate (6598-63-6)having Reliability Index: 0.55(moderate prediction quality).

In another experimental study conducted by U.S. National Library of Medicine (Chemidplus Database,U.S. National Library of Medicine,2017) for the structurally similar read across substance2-Naphthalenesulfonic acid, 3-((4-(acetylamino)phenyl)azo)-4-hydroxy-7-((((5-hydroxy-6-(pheny-lazo)-7-sulfo-2-naphthalenyl)amino)carbonyl)amino)-,disodium salt (3441-14-3).Acute oral toxicity study was done in rats using test material 2-Naphthalenesulfonic acid, 3-((4-(acetylamino)phenyl)azo)-4-hydroxy-7-((((5-hydroxy-6-(phenylazo)-7-sulfo-2-naphthalenyl)amino)carbonyl)amino)-, disodium salt (3441-14-3).No Mortality was observed at dose 5000 mg/kg bw. Clinical signs like changes in urine composition, somnolence (general depressed activity) were observed and after systemic exposure to skin and appendages (skin) dermatitis was observed. Gross pathology was performed on kidney, ureter, and bladder.Hence,LD50 value was considered to be >5000 mg/kg bw,when rats were treated with 2-Naphthalenesulfonic acid, 3-((4-(acetylamino)phenyl)azo)-4-hydroxy-7-((((5-hydroxy-6-(phenylazo)-7-sulfo-2-naphthalenyl)amino)carbonyl)amino)-, disodium salt (3441-14-3) orally.

Also these results are further supported by the experimental study conducted by U.S. National Library of Medicine (ChemIDplus TOXNET Database, 2017) for the structurally similar read across substance2-Naphthalenesulfonic acid, 3-((4-(acetylamino)phenyl)azo)-4-hydroxy-7-((((5-hydroxy-6-(pheny-lazo)-7-sulfo-2-naphthalenyl)amino)carbonyl)amino)-,disodium salt (3441-14-3).Acute oral toxicity study was done in mouse using test material 2-Naphthalenesulfonic acid, 3-((4-(acetylamino)phenyl)azo)-4-hydroxy-7-((((5-hydroxy-6-(phenylazo)-7-sulfo-2-naphthalenyl)amino)carbonyl)amino)-,disodium salt (3441-14-3).No Mortality was observed at dose 5000 mg/kg bw. Clinical signs like changes in urine composition,somnolence (general depressed activity) were observed and after systemic exposure to skin and appendages (skin) dermatitis was observed. Gross pathology was performed on kidney, ureter, and bladder.Hence,LD50 value was considered to be >5000 mg/kg bw,when mouse were treated with 2-Naphthalenesulfonic acid, 3-((4-(acetylamino)phenyl)azo)-4-hydroxy-7-((((5-hydroxy-6-(phenylazo)-7-sulfo-2-naphthalenyl)amino)carbonyl)amino)-, disodium salt (3441-14-3)orally.

Also these results are further supported by the experimental study conducted by U.S. National Library of Medicine (ChemIDplus TOXNET Database, 2017) for the structurally similar read across substance 1,4-Benzenedisulfonic acid,2,2'-(1,2-ethenediylbis((3-sulfo-4,1-phenylene)imino(6-(diethylamino)-1,3,5-triazine-4,2-diyl)imino))bis-,hexasodium salt (41098-56-0). Acute oral toxicity study was done in rats using test material1,4-Benzenedisulfonic acid,2,2'-(1,2-ethenediylbis((3-sulfo-4,1-phenylene)imino(6-(diethylamino)-1,3,5-triazine-4,2-diyl)imino))bis-,hexasodium salt (41098-56-0).50% Mortality was observed at dose 11320 mg/kg bw. Hence,LD50 value was considered to be 11320 mg/kg bw,when rats were treated with 1,4-Benzenedisulfonic acid,2,2'-(1,2-ethenediylbis((3-sulfo-4,1-phenylene)imino(6-(diethylamino)-1,3,5-triazine-4,2-diyl)imino))bis-,hexasodium salt (41098-56-0) orally.

Thus, based on the above studies and predictions on Trisodium 4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato-2-naphthyl]amino]carbonyl]amino]-3-sulphonato-2-naphthyl]azo]benzoate (6598-63-6) and its read across substances, it can be concluded that LD50 value was 4438.20 mg/kg bw. Thus, comparing this value with the criteria of CLPregulation,Trisodium 4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato-2-naphthyl]amino]carbonyl]amino]-3-sulphonato-2-naphthyl]azo]benzoate (6598-63-6) can be “Not classified” for Acute Oral Toxicity.

Acute Dermal Toxicity:

In different studies, Trisodium 4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato-2-naphthyl]amino]carbonyl]amino]-3-sulphonato-2-naphthyl]azo]benzoate (6598-63-6) has been investigated for acute dermal toxicity to a greater or lesser extent. Often the studies are based on in vivo experiments and estimated data in rodents, i.e. most commonly in rabbits for Trisodium 4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato-2-naphthyl]amino]carbonyl]amino]-3-sulphonato-2-naphthyl]azo]benzoate (6598-63-6). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for Trisodium 4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato-2-naphthyl]amino]carbonyl]amino]-3-sulphonato-2-naphthyl]azo]benzoate (6598-63-6).The LD50 was estimated to be 10239.41 mg/kg bw,when male and female Vienna White rabbits were exposed semiocclusively with Trisodium 4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato-2-naphthyl]amino]carbonyl]amino]-3-sulphonato-2-naphthyl]azo]benzoate (6598-63-6)by dermal application for 24 hours.

In another experimental study conducted by EUROPEAN COMMISSION – European Chemicals Bureau (IUCLID DATASET, EUROPEAN COMMISSION – European Chemicals Bureau, 18–FEB–2000) for the structurally similar read across substance Sodium carbonate (497–19–8). In acute dermal toxicity study, mice were treated with Sodium carbonate(497–19–8)in the concentration of 2210 mg/kg bw by dermal application.50% mortality was observed in treated mice at dose 2210 mg/kg bw. Therefore, LD50 value was considered to be 2210 mg/kg bw,when mice were treated with Sodium carbonate(497–19–8)  by dermal application.

Also these results are further supported by the experimental study conducted by Inventory Multi-Tiered Assessment and Prioritisation (IMAP) - the National Industrial Chemicals Notification and Assessment Scheme (NICNAS) (Human Health Tier II Assessment for Alkaline Salts-Carbonates, the National Industrial Chemicals Notification and Assessment Scheme (NICNAS),2017) for the structurally similar read across substance Potassium carbonate (584-08-7). In acute dermal toxicity study, rats were treated with Potassium carbonate(584-08-7) in the concentration of 2000 mg/kg bw by dermal application. No mortality was observed in treated rats at dose 2000 mg/kg bw. No systemic effects were observed following dermal exposure to potassium carbonate. Local severe skin irritation (severe erythema and oedema) was seen at the application site. Therefore, LD50 value was considered to be >2000 mg/kg bw,when rats were treated with Potassium carbonate(584-08-7) by dermal application.

Thus, based on the above studies and predictions on Trisodium 4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato-2-naphthyl]amino]carbonyl]amino]-3-sulphonato-2-naphthyl]azo]benzoate (6598-63-6)and its read across substances, it can be concluded that LD50 value was 10239.41 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Trisodium 4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato-2-naphthyl]amino]carbonyl]amino]-3-sulphonato-2-naphthyl]azo]benzoate (6598-63-6) can be “Not classified” for Acute Dermal Toxicity.

Justification for classification or non-classification

Thus, comparing this value with the criteria of CLP regulation,Trisodium 4-[[1-hydroxy-6-[[[[5-hydroxy-6-(phenylazo)-7-sulphonato-2-naphthyl]amino]carbonyl]amino]-3-sulphonato-2-naphthyl]azo]benzoate (6598-63-6) can be “Not classified” for Acute Oral and Dermal Toxicity.