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Description of key information

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, repeated dose oral toxicity was predicted for the test compound 2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo]-1- naphthyl]azo]-6-sulpho-1- naphthyl]azo]benzene-1,4-disulphonic acid, magnesium sodium salt (93941-74-3). The study assumed the use of male and female Charles River CR strain rat in chronic study of 90days. No significant alterations were noted at the dose level of 1148.5583mg/Kg bw/day. The predicted No Observed Adverse Effect Level (NOAEL) for compound 2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo]- 1-naphthyl]azo]-6-sulpho-1-naphthyl]azo]benzene-1,4-disulphonic acid, magnesium sodium salt is considered to be 1148.558mg/Kg bw/day. Based on this value it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
repeated dose toxicity: oral
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:
Prediction is done using OECD QSAR Toolbox version 3.3 and the supporting QMRF report has been attached.
Qualifier:
according to
Guideline:
other: As mention below
Principles of method if other than guideline:
Prediction is done using OECD QSAR Toolbox version 3.3, 2018.
GLP compliance:
not specified
Limit test:
no
Specific details on test material used for the study:
Name: 2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo]-1-naphthyl]azo]-6-sulpho-1-naphthyl]azo]benzene-1,4-disulphonic acid, magnesium sodium salt
SMILES:[Mg]_[Na]_Oc1c2ccc(Nc3ccccc3)cc2cc(S(O)(=O)=O)c1N=Nc1ccc(N=Nc2ccc(N=Nc3cc(S(O)(=O)=O)ccc3S(O)(=O)=O)c3ccc(S(O)(=O)=O)cc23)c2ccccc12
InChI:1S/C42H29N7O13S4.Mg.Na/c50-42-29-13-10-26(43-25-6-2-1-3-7-25)20-24(29)21-40(66(60,61)62)41(42)49-47-35-16-15-34(30-8-4-5-9-31(30)35)44-46-37-18-17-36(32-14-11-27(22-33(32)37)63(51,52)53)45-48-38-23-28(64(54,55)56)12-19-39(38)65(57,58)59;;/h1-23,43,50H,(H,51,52,53)(H,54,55,56)(H,57,58,59)(H,60,61,62);;/q;+2;+1/p-3/b46-44+,48-45+,49-47+;;
Molecular Formula: C42H29N7O13S4.xMg.xNa
Molecular Weight: 1012.2624 g/mole
Species:
rat
Strain:
other: Charles River CR strain
Sex:
male/female
Details on test animals and environmental conditions:
Not specified.
Route of administration:
oral: gavage
Details on route of administration:
Not specified.
Vehicle:
not specified
Details on oral exposure:
Not specified.
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
Not specified.
Duration of treatment / exposure:
90 days
Frequency of treatment:
Not specified.
Remarks:
Not specified.
No. of animals per sex per dose:
Not specified.
Control animals:
not specified
Details on study design:
Not specified.
Positive control:
Not specified.
Observations and examinations performed and frequency:
Not specified.
Sacrifice and pathology:
Not specified.
Other examinations:
Not specified.
Statistics:
Not specified.
Clinical signs:
not specified
Mortality:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified
Details on results:
Not specified.
Dose descriptor:
NOAEL
Effect level:
1 148.558 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No significant effect were observed at this dose
Remarks on result:
other: No toxic effect were observed
Critical effects observed:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

The prediction was based on dataset comprised from the following descriptors: NOAEL
Estimation method: Takes average value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

((((((((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and ("m" and ( not "n") )  )  and ("o" and ( not "p") )  )  and ("q" and ( not "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 Aromatic compound OR Azo compound OR Hydroxy compound OR Phenol OR Secondary amine OR Secondary aromatic amine OR Sulfonic acid 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 Alcohol, olefinic attach [-OH] OR Aliphatic Nitrogen, one aromatic attach [-N] OR Aliphatic Nitrogen, two aromatic attach [-N-] OR Aromatic Carbon [C] OR Azo [-N=N-] OR Hydroxy, aromatic attach [-OH] OR Hydroxy, sulfur attach [-OH] OR Magnesium [Mg] OR Miscellaneous sulfide (=S) or oxide (=O) OR Nitrogen, two or tree olefinic attach [>N-] OR No functional group found OR Olefinic carbon [=CH- or =C<] OR Oxygen, one aromatic attach [-O-] OR Suflur {v+4} or {v+6} OR Sulfinic acid [-S(=O)OH] OR Sulfonate, aromatic attach [-SO2-O] 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 No functional group found OR Overlapping groups OR Phenol 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 Sulfonic acid by Organic Functional groups ONLY

Domain logical expression index: "e"

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

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Carbamoylation after isocyanate formation OR AN2 >> Carbamoylation after isocyanate formation >> N-Hydroxylamines OR Michael addition OR Michael addition >> Quinone type compounds OR Michael addition >> Quinone type compounds >> Quinone methides OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Hydrazine Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> N-Hydroxylamines OR Radical >> ROS formation after GSH depletion OR Radical >> ROS formation after GSH depletion >> Quinone methides OR SN1 OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> N-Hydroxylamines by DNA binding by OASIS v.1.3

Domain logical expression index: "g"

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

Domain logical expression index: "h"

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 SN1 OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine by DNA binding by OECD

Domain logical expression index: "i"

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

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Moderate binder, NH2 group OR Moderate binder, OH grooup OR Non binder, impaired OH or NH2 group OR Non binder, without OH or NH2 group OR Strong binder, OH group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as No Data by Ultimate biodeg

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as > 100 days OR 1 to 10 days by Ultimate biodeg

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CNS Surface Tension > 62 mN/m AND Exclusion rules not met AND Group All Melting Point > 200 C AND Group CNS Melting Point > 120 C AND Group CNS Melting Point > 50 C AND Group CNS Molecular Weight > 620 g/mol by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as (!Undefined)Group C Surface Tension > 62 mN/m OR Group All log Kow > 9 OR Group C Aqueous Solubility < 0.0001 g/L OR Group C Melting Point > 55 C OR Group C Molecular Weight > 350 g/mol OR Group C Vapour Pressure < 0.0001 Pa by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "o"

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

Domain logical expression index: "p"

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

Domain logical expression index: "q"

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

Domain logical expression index: "r"

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

Domain logical expression index: "s"

Similarity boundary:Target: [Mg]_[Na]_Oc1c2ccc(Nc3ccccc3)cc2cc(S(O)(=O)=O)c1N=Nc1ccc(N=Nc2ccc(N=Nc3cc(S(O)(=O)=O)ccc3S(O)(=O)=O)c3ccc(S(O)(=O)=O)cc23)c2ccccc12
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] AND Aliphatic Nitrogen, one aromatic attach [-N] AND Aliphatic Nitrogen, two aromatic attach [-N-] AND Aromatic Carbon [C] AND Azo [-N=N-] AND Hydroxy, aromatic attach [-OH] AND Hydroxy, sulfur attach [-OH] AND Magnesium [Mg] AND Miscellaneous sulfide (=S) or oxide (=O) AND Nitrogen, two or tree olefinic attach [>N-] AND No functional group found AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] AND Suflur {v+4} or {v+6} AND Sulfinic acid [-S(=O)OH] AND Sulfonate, aromatic attach [-SO2-O] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "u"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.227

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.97

Conclusions:
The predicted No Observed Adverse Effect Level (NOAEL) for 2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo]-1-naphthyl]azo]-6-sulpho-1-naphthyl]azo]benzene-1,4-disulphonic acid, magnesium sodium salt (93941-74-3) is considered to be 1148.558 mg/Kg bw/day.
Executive summary:

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, repeated dose oral toxicity was predicted for the test compound 2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo] -1-naphthyl]azo]-6-sulpho-1- naphthyl]azo]benzene- 1,4-disulphonic acid, magnesium sodium salt (93941-74-3). The study assumed the use of male and female Charles River CR strain in chronic study of 90days. No significant alterations were noted at the dose level of 1148.5583mg/Kg bw/day. The predicted No Observed Adverse Effect Level (NOAEL) for compound 2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo]-1-naphthyl]azo]-6-sulpho-1-naphthyl]azo]benzene-1,4-disulphonic acid, magnesium sodium salt is considered to be 1148.558mg/Kg bw/day. Based on this value it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 148.558 mg/kg bw/day
Study duration:
chronic
Species:
rat
Quality of whole database:
K2 prediction from OECD QSAR toolbox 3.3 version.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Repeated dose toxicity: via oral route;

Various experimental studies were reviewed to determine the toxic nature of target substance 2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo]-1- naphthyl]azo]-6 sulpho-1-naphthyl]azo] benzene-1 ,4-disulphonic acid, magnesium sodium salt (93941-74-3) upon repeated exposure by oral route. The studies are as mentioned below:

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, repeated dose oral toxicity was predicted for the test compound 2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo]-1- naphthyl]azo]-6-sulpho-1- naphthyl]azo]benzene-1,4-disulphonic acid, magnesium sodium salt (93941-74-3). The study assumed the use of male and female Charles River CR strain rat in chronic study of 90days. No significant alterations were noted at the dose level of 1148.5583mg/Kg bw/day. The predicted No Observed Adverse Effect Level (NOAEL) for compound 2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo]-1-naphthyl]azo]-6-sulpho-1-naphthyl]azo]benzene-1,4-disulphonic acid, magnesium sodium salt is considered to be 1148.558mg/Kg bw/day. Based on this value it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

Another chronic toxicity study for Read across was performed by J.-P. DRAKE et al.( Food and cosmetics toxicology,1977) to determine the oral toxic nature of tetrasodium 4-acetamido-5-hydroxy-6-({7-sulfonato-4-[(4-sulfonatophenyl)diazenyl]-1-naphthyl}diazeny...(2519-30-4). The read across substances share high similarity in structure and log kow .Therefore, it is acceptable to derive information on toxicity from the analogue substance. Repeated dose toxicity test were performed on mice with different concentrations from 0.1, 0.25,0.5 or 1.0% (130,325,650,1300 mg/kg bw/d)Black PN for 80 wk. 30 males and 30 females was used for the treatment and group of 60 mice of each sex as control. The general condition and behaviour of the animals were observed frequently and any mouse that showed signs of ill-health was isolated, to be returned to its cage on recovery or to be killed if its condition deteriorated. The mice were weighed at the start of the experiment, at wk 3 and then at intervals of 2 wk until wk 73 of the experiment. Blood sample were taken at wk 28 and 55.At 80 wk, blood samples were collected from the aorta of all surviving mice during the autopsy. For haematology blood samples were collected and for urine sample from 6-hr period from three groups of five mice of each sex from the controls and the groups on the two highest dietary levels of Black PN. Histopathology was also conducted. There were no dose-related effects on body-weight gain, haematology or organ weights. The incidence of histopathological findings, including tumours, was not altered by the feeding of Black PN. Therefore, the endpoint for the repeated dose toxicity was found to be NOAEL at 1 % (1300 mg/kg/day) concentration of Black PN to mice.

Repeated inhalation study:

According to Annex IX of the REACH regulation, testing by the inhalation route is appropriate only if exposure of humans via inhalation is likely. Taking into account the low vapour pressure of the substance 2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo]-1-naphthyl]azo]-6-sulpho-1-naphthyl]azo] benzene-1 ,4-disulphonic acid, magnesium sodium salt (93941-74-3),which is reported as 1.6132E-17 Pa at 25 C. Also considering the particle size distribution of the substance the majority of the particles was found to be in the size of 150 micron to 53 micron which is much larger size range compared to the inhalable particulate matter. Thus, exposure to inhalable dust, mist and vapour of the chemical2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo]-1-naphthyl]azo]-6-sulpho-1-naphthyl]azo] benzene-1 ,4-disulphonic acid, magnesium sodium salt is highly unlikely. Therefore this study is considered for waiver.

 

Repeated dermal study

The acute toxicity value for 2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo]-1-naphthyl]azo]-6-sulpho-1-naphthyl]azo] benzene-1 ,4-disulphonic acid, magnesium sodium salt (93941-74-3) (as provided in section 7.2.3) is 13739.0mg/kg body weight. Also, given the use of the chemical; repeated exposure by the dermal route is unlikely since the use of gloves is common practice in industries. Thus, it is expected that 2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo]-1-naphthyl]azo]-6-sulpho-1-naphthyl]azo] benzene-1 ,4-disulphonic acid, magnesium sodium salt shall not exhibit 28 day repeated dose toxicity by the dermal route. In addition, there is no data available that suggests that 2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo]-1-naphthyl]azo]-6-sulpho-1-naphthyl]azo] benzene-1 ,4-disulphonic acid, magnesium sodium salt shall exhibit repeated dose toxicity by the dermal route. Hence this end point was considered for waiver.

 

Based on the data available for the target chemical and its prediction, 2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo]-1-naphthyl]azo]-6-sulpho-1-naphthyl]azo] benzene-1 ,4-disulphonic acid, magnesium sodium salt does not exhibit toxic nature upon repeated exposure by oral, inhalation and dermal route of exposure and hence is not likely to classify as per the criteria mentioned in CLP regulation.

Justification for classification or non-classification

Based on the data available for the target chemical and its prediction, 2-[[4-[[4-[[6-anilino-1-hydroxy-3-sulpho-2-naphthyl]azo]-1-naphthyl]azo]-6-sulpho-1-naphthyl]azo] benzene-1 ,4-disulphonic acid, magnesium sodium salt does not exhibit toxic nature upon repeated exposure by oral, inhalation and dermal route of exposure and hence is not likely to classify as per the criteria mentioned in CLP regulation.