Disodium 4,4'-[[2,4-dihydroxy-5-(hydroxymethyl)-1,3-phenylene]bis(azo)]bisnaphthalene-1-sulphonate

Endpoint summary

Description of key information

Acute toxicity: oral
The median lethal dose (LD50) for the substance Disodium 4,4'-[[2,4-dihydroxy-5-(hydroxymethyl)-1,3-phenylene]bis(azo)]bisnaphthalene-1-sulphonate is determined to be > 2000 mg/Kg in female Evans albino mice.

Acute toxicity: inhalation
In accordance with column 2 of Annex VIII of the REACH regulation, testing by the inhalation route is appropriate if exposure of humans via inhalation is likely taking into account the vapour pressure of the substance. This chemical has a very low vapour pressure of 1.48E-33 Pascal at 25°C and thus exposure by the inhalation route for this chemical is unlikely.

Acute toxicity: dermal
The median lethal dose (LD50) for the substance Disodium 4,4'-[[2,4-dihydroxy-5-(hydroxymethyl)-1,3-phenylene]bis(azo)]bisnaphthalene-1-sulphonate is estimated to be 35636.23 mg/Kg in rabbits via dermal route.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

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 a peer reviewed publication

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Aqueous solutions of Chocolate Brown HT in a dose volume of 10 ml/kg were administered to groups of 10 mice by oral intubation. Survivors were observed and number of deaths noted for 14 days.

GLP compliance:

not specified

Test type:

other: No data available

Species:

mouse

Strain:

other: Evans Albino

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: No data available
- Age at study initiation: No data available
- Weight at study initiation: 16-20 g
- Fasting period before study: 18 hrs
- Housing: No data available
- Diet (e.g. ad libitum): No data available
- Water (e.g. ad libitum): No data available
- Acclimation period: No data available

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data available
- Humidity (%):No data available
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): No data available

IN-LIFE DATES: From: To: No data available

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

Aqueous solutions of Chocolate Brown HT in a dose volume of 10 ml/kg were administered.

Doses:

upto 2000 mg/kg

No. of animals per sex per dose:

10

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: No data available
- Necropsy of survivors performed: yes/no
- Other examinations performed: mortality, clinical signs, urine analysis
other:

Statistics:

The acute LD50 value was calculated by the method of Litchfield & Wilcoxon (1949)

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No death observed during the observation period

Clinical signs:

other: Brown coloration especially of the extremities was observed

Gross pathology:

No data available

Other findings:

Elimination of orally-administered Chocolate Brown HT proceeded slowly, as evidenced by the persistence of brown colouring in the urine after a single dose

Interpretation of results:

GHS criteria not met

Conclusions:

The median lethal dose (LD50) for the substance Disodium 4,4'-[[2,4-dihydroxy-5-(hydroxymethyl)-1,3-phenylene]bis(azo)]bisnaphthalene-1-sulphonate is determined to be > 2000 mg/Kg in female Evans albino mice.

Executive summary:

Acute toxicity study was conducted on 10 female Evans albino mice for the test material Chocolate Brown HT ( Disodium 4,4'-[[2,4-dihydroxy-5-(hydroxymethyl)-1,3-phenylene]bis(azo)]bisnaphthalene-1-sulphonate). Aqueous solution of the test material was administered at a dose volume of 10mL/Kg to the mice by oral intubation. On the basis of mortality, clinical signs observed and urinalysis performed, the LD50 for the given test material is determined to be >2000 mg/Kg. This value indicates that the substance is non-toxic by oral route as per the CLP criteria.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Data is of K2 level from a peer reviewed publication

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

(Q)SAR

Adequacy of study:

key study

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:

The prediction is done using QSAR Toolbox version 3.3 and thr supportig QMRF has been attached.

Principles of method if other than guideline:

The prediction is done using QSAR Toolbox version 3.

GLP compliance:

no

Test type:

standard acute method

Species:

rabbit

Strain:

not specified

Sex:

not specified

Type of coverage:

not specified

Vehicle:

not specified

Duration of exposure:

24 hr

Doses:

no data available

No. of animals per sex per dose:

no data available

Control animals:

not specified

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

35 636.23 mg/kg bw

Based on:

test mat.

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" )  and ("f" and ( not "g") )  )  and ("h" and ( not "i") )  )  and ("j" and "k" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Naphthalene sulfonic acids, condensates by OECD HPV Chemical Categories

Domain logical expression index: "b"

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

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Non binder, MW>500 by Estrogen Receptor Binding

Domain logical expression index: "d"

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

Domain logical expression index: "e"

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

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as 1,2-aminoalcohol OR 1,2-diol OR Acetal OR Aldehyde OR Alkene OR Alkyl bromide OR Alkyl chloride OR Alkyl fluoride OR Alkyl halide OR Alkylarylether OR Alkylthiol OR Alkyne OR Alpha-hydroxyacid OR Amine OR Aryl bromide OR Aryl chloride OR Aryl fluoride OR Aryl halide OR Carbamic acid ester (uretane) OR Carbonic acid derivative OR Carbonic acid diester OR Carbonic acid ester halide OR Carbonyl compound OR Carboxylic acid OR Carboxylic acid amide OR Carboxylic acid anhydride OR Carboxylic acid derivative OR Carboxylic acid ester OR Carboxylic acid orthoester OR Carboxylic acid prim. amide OR Carboxylic acid salt OR Carboxylic acid sec. amide OR Carboxylic acid tert. amide OR CO2 derivative (general) OR Dialkylether OR Diarylether OR Disulfide OR Enolether OR Ether OR Guanidine OR Halogen derivative OR Hemiacetal OR Heterocyclic compound OR Hydroperoxide OR Hydroxylamine OR Imine OR Isothiourea OR Ketone OR Lactam OR Lactone OR Nitrate OR Nitrile OR Nitro compound OR No functional group found OR N-oxide OR Orthocarboxylic acid derivative OR Oxime OR Peroxide OR Phosphine OR Phosphinoxide OR Phosphonic acid OR Phosphonic acid derivative OR Phosphonic acid ester OR Phosphoric acid OR Phosphoric acid derivative OR Phosphoric acid ester OR Primary aliphatic amine OR Primary amine OR Primary aromatic amine OR Quaternary ammonium salt OR Secondary alcohol OR Secondary aliphatic amine OR Secondary amine OR Secondary aromatic amine OR Sulfenic acid derivative OR Sulfonic acid OR Sulfonyl halide OR Sulfuric acid derivative OR Tertiary alcohol OR Tertiary aliphatic amine OR Tertiary amine OR Thiocarbonic acid derivative OR Thioether OR Thiol OR Thiolactone OR Thiophosphoric acid amide OR Thiophosphoric acid derivative OR Thiophosphoric acid ester OR Thiourea by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Alkane branched with quaternary carbon OR Alkane, branched with tertiary carbon OR Alkene OR Alkoxy OR AlkoxySilane OR Alkyl arenes OR Alkyne OR Allyl OR Alpha,beta unsaturated aldehyde OR Benzotriazole OR Biphenyl OR Cycloalkane OR Ether OR Fused heterocyclic aromatic OR Fused saturated heterocycles OR Heterocyclic Phenol OR Heterocyclic spiro rings OR Isopropyl OR Ketone OR No functional group found OR Phosphite ester OR Pyridine OR Quinoline/ Isoquinoline OR Saturated heterocyclic fragment OR Silane OR tert-Butyl OR Tetralin OR Thiophosphate OR Tin, organo OR Triazine OR Unsaturated heterocyclic amine OR Unsaturated heterocyclic fragment by Organic Functional groups

Domain logical expression index: "j"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.269

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.03

Interpretation of results:

GHS criteria not met

Conclusions:

The median lethal dose (LD50) for the substance Disodium 4,4'-[[2,4-dihydroxy-5-(hydroxymethyl)-1,3-phenylene]bis(azo)]bisnaphthalene-1-sulphonate is estimated to be 35636.23 mg/Kg in rabbits via dermal route.

Executive summary:

The acute toxicity by dermal route of Disodium 4,4’-(2,4-dihydroxy-5- hydroxymethyl-1,3-phenylene bis-azo) di- (naphthalene-1-sulfonate) is estimated using QSAR Toolbox version 3.3. The median lethal dose (LD50) for the substance Disodium 4,4'-[[2,4-dihydroxy-5-(hydroxymethyl)-1,3-phenylene]bis(azo)]bisnaphthalene-1-sulphonate is estimated to be 35636.23 mg/Kg in rabbits via dermal route. This value indicates that the substance is not likely to exhibit toxicity by dermal route as per the CLP criteria.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

35 636.23 mg/kg bw

Quality of whole database:

Data is of K2 level estimated using OECD QSAR Toolbox (v 3.3)

Additional information

Acute toxicity: oral
No. of studies of Chocolate Brown HT and its read across substance were reviewed for acute toxicity by oral route from reliable sources having Klimisch rating 2. The summary is represented as below:

For key study of target, Acute toxicity study was conducted on 10 female Evans albino mice for the Chocolate Brown HT (Disodium 4,4'-[[2,4-dihydroxy-5-(hydroxymethyl)-1,3-phenylene]bis(azo)]bisnaphthalene-1-sulphonate). Aqueous solution of the test material was administered at a dose volume of 10mL/Kg to the mice by oral intubation. On the basis of mortality, clinical signs observed and urinalysis performed, the LD50 for the given test material is determined to be >2000 mg/Kg. This value indicates that the substance is non-toxic by oral route as per the CLP criteria.

Similarly in supporting study of the target, Acute toxicity study was conducted on 5 male and female Porton SPF Wistar rats for the Chocolate Brown HT (Disodium 4,4'-[[2,4-dihydroxy-5-(hydroxymethyl)-1,3-phenylene]bis(azo)]bisnaphthalene-1-sulphonate). Aqueous solution of the test material was administered at a dose volume of 10mL/Kg to the rats by oral intubation. On the basis of mortality, clinical signs observed and urinalysis performed, the LD50 for the given test material is determined to be >2000 mg/Kg. This value indicates that the substance is non-toxic by oral route as per the CLP criteria.

Further in supporting data from Read across substance (CAS 3567-69-9), Acute oral toxicity study was conducted on mouse for the test material Azorubine (Disodium 4-hydroxy-3-[(4-sulphonatonaphthyl)azo]naphthalenesulphonate). The median lethal dose (LD50) for the substance was determined to be> 8000 mg/Kg. This value indicates that the substance is not toxic to mouse and hence is not classified under Acute oral toxicity. 

Similarly, Acute oral toxicity study was conducted on rat for the same read across substance (CAS 3567-69-9) i.e. Azorubine (Disodium 4-hydroxy-3-[(4-sulphonatonaphthyl)azo]naphthalenesulphonate). The median lethal dose (LD50) for the substance was determined to be > 10000 mg/Kg. This value indicates that the substance is not toxic to rat and hence is not classified under Acute oral toxicity. 

Considering all the above values, the target substance Chocolate Brown HT (Disodium 4,4'-[[2,4-dihydroxy-5-(hydroxymethyl)-1,3-phenylene]bis(azo)]bisnaphthalene-1-sulphonate) is not likely exhibit acute toxicity via oral route as per CLP regulation.

Acute toxicity: inhalation
In accordance with column 2 of Annex VIII of the REACH regulation, testing by the inhalation route is appropriate if exposure of humans via inhalation is likely taking into account the vapour pressure of the substance. This chemical has a very low vapour pressure of 1.48E-33 Pascal at 25°C and thus exposure by the inhalation route for this chemical is unlikely.

Acute toxicity: dermal
The acute toxicity by dermal route of Disodium 4,4’-(2,4-dihydroxy-5- hydroxymethyl-1,3-phenylene bis-azo) di- (naphthalene-1-sulfonate) is estimated using QSAR Toolbox version 3.3. The median lethal dose (LD50) for the substance Disodium 4,4'-[[2,4-dihydroxy-5-(hydroxymethyl)-1,3-phenylene]bis(azo)]bisnaphthalene-1-sulphonate is estimated to be 35636.23 mg/Kg in rabbits via dermal route. This value indicates that the substance is not likely to exhibit toxicity by dermal route as per the CLP criteria.

Justification for classification or non-classification

Based on the available information from reliable sources, the substance is likely to be non-toxic by oral and dermal route as per the CLP criteria.