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EC number: 249-352-9 | CAS number: 28983-56-4
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Description of key information
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 Disodium [[4-[bis[4-[(sulphonatophenyl) amino]phenyl] methylene]cyclohexa-2,5-dien-1-ylidene]amino]ben..(28983-56-4 ). The study assumed the use of male and female Wistar strain in Subchronic study. No significant alterations were noted at the dose level of 815.90mg/Kg bw/day. The predicted No Observed Adverse Effect Level (NOAEL) for compound Disodium [[4-[bis[4-[(sulphonatophenyl) amino]phenyl] methylene]cyclohexa-2,5-dien-1-ylidene]amino]ben..is considered to be 815.90mg/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
- Endpoint:
- repeated dose toxicity: oral, other
- 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
- 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 of test material :Methyl Blue
- Molecular formula : C37H26N3Na2O9S3
- Molecular weight : 800.8182 g/mol
- Smiles notation : c1cc(ccc1C(=C2C=CC(=[NH+]c3ccc (cc3)S(=O) (=O)[O-])C=C2)c4ccc(cc4)Nc5ccc(cc5)S (=O)(=O)[O-])Nc6ccc(cc6)S(=O)(=O)O.[Na+].[Na+]
- InChl : 1S/C37H29N3O9S3.2Na/c41-50(42,43)34-19-13-31(14-20-34)38-28-7-1-25(2-8-28)37(26-3-9-29(10-4-26)39-32-15-21-35(22-16-32)51(44,45 46)27-5-11-30(12-6-27)40-33-17-23-36(24-18-33)52(47,48)49;;/h1-24,38-39H,(H,41,42,43)(H,44,45,46)(H,47,48,49);;/q;2*+1/p-1
- Substance type: Organic
- Physical state: Solid - Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system 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:
- 80 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
- Dose descriptor:
- NOAEL
- Effect level:
- 815.9 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No significant effect were observed at this dose.
- Critical effects observed:
- not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Conclusions:
- The predicted No Observed Adverse Effect Level (NOAEL) for Disodium [[4-[bis[4-[(sulphonatophenyl)amino]phenyl]methylene]cyclohexa-2,5-dien-1-ylidene]amino]ben..(28983-56-4 )is considered to be 815.90mg/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 Disodium [[4-[bis[4-[(sulphonatophenyl) amino]phenyl] methylene]cyclohexa-2,5-dien-1-ylidene]amino]ben..(28983-56-4 ). The study assumed the use of male and female Wistar strain in Subchronic study. No significant alterations were noted at the dose level of 815.90mg/Kg bw/day. The predicted No Observed Adverse Effect Level (NOAEL) for compound Disodium [[4-[bis[4-[(sulphonatophenyl) amino]phenyl] methylene]cyclohexa-2,5-dien-1-ylidene]amino]ben..is considered to be 815.90mg/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.
Reference
The
prediction was based on dataset comprised from the following
descriptors: NOAEL
Estimation method: Takes average value from the 5 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 ("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 "u" )
and ("v"
and "w" )
)
Domain
logical expression index: "a"
Referential
boundary: The
target chemical should be classified as Alkene OR Ammonium salt OR
Aromatic amine OR Aryl OR Sulfonic acid by Organic Functional groups ONLY
Domain
logical expression index: "b"
Referential
boundary: The
target chemical should be classified as Alkene OR Ammonium salt OR
Aromatic amine OR Aryl OR Overlapping groups OR Sulfonic acid by Organic
Functional groups (nested) ONLY
Domain
logical expression index: "c"
Referential
boundary: The
target chemical should be classified as Aliphatic Nitrogen, two aromatic
attach [-N-] OR Aromatic Carbon [C] OR Miscellaneous sulfide (=S) or
oxide (=O) OR Nitrogen, hydrogen attach {v+5} OR Nitrogen, two or tree
olefinic attach [>N-] OR Olefinic carbon [=CH- or =C<] OR
Ortho-substitutes on N=C<, aromatic OR Suflur {v+4} or {v+6} OR
Sulfonate, aromatic attach [-SO2-O] by Organic functional groups (US
EPA) ONLY
Domain
logical expression index: "d"
Referential
boundary: The
target chemical should be classified as Amine OR Anion OR Aromatic
compound OR Cation OR Secondary amine OR Secondary aromatic amine OR
Sulfonic acid derivative by Organic functional groups, Norbert Haider
(checkmol) ONLY
Domain
logical expression index: "e"
Referential
boundary: The
target chemical should be classified as No alert found by DNA binding by
OECD
Domain
logical expression index: "f"
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 >> Arenes OR Michael addition >> P450
Mediated Activation to Quinones and Quinone-type Chemicals >> Polycyclic
(PAHs) and heterocyclic (HACs) aromatic hydrocarbons-Michael addition OR
Michael addition >> Polarised Alkenes-Michael addition OR Michael
addition >> Polarised Alkenes-Michael addition >> Alpha, beta-
unsaturated ketones OR SN1 OR SN1 >> Carbenium Ion Formation OR SN1 >>
Carbenium Ion Formation >> Polycyclic (PAHs) and heterocyclic (HACs)
aromatic hydrocarbons-SN1 OR SN1 >> Nitrenium Ion formation OR SN1 >>
Nitrenium Ion formation >> Tertiary aromatic amine by DNA binding by OECD
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 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 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 Class 5 (Not possible to
classify according to these rules) by Acute aquatic toxicity
classification by Verhaar (Modified) ONLY
Domain
logical expression index: "j"
Referential
boundary: The
target chemical should be classified as Inclusion rules not met by Skin
irritation/corrosion Inclusion rules by BfR
Domain
logical expression index: "k"
Referential
boundary: The
target chemical should be classified as Quaternary organic ammonium
compounds by Skin irritation/corrosion Inclusion 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 (!Undefined)Group CNS Surface Tension > 62
mN/m AND Group All log Kow < -3.1 AND Group All Melting Point > 200 C
AND Group CNS log Kow < 0.5 AND Group CNS log Kow < -2 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: "m"
Referential
boundary: The
target chemical should be classified as Group All log Kow > 9 by Skin
irritation/corrosion Exclusion rules by BfR
Domain
logical expression index: "n"
Referential
boundary: The
target chemical should be classified as Alkali Earth AND Non-Metals by
Groups of elements
Domain
logical expression index: "o"
Referential
boundary: The
target chemical should be classified as Halogens by Groups of elements
Domain
logical expression index: "p"
Referential
boundary: The
target chemical should be classified as Alkali Earth AND Non-Metals by
Groups of elements
Domain
logical expression index: "q"
Referential
boundary: The
target chemical should be classified as Metals by Groups of elements
Domain
logical expression index: "r"
Referential
boundary: The
target chemical should be classified as Not categorized by Repeated dose
(HESS)
Domain
logical expression index: "s"
Referential
boundary: The
target chemical should be classified as Aliphatic nitriles
(Hepatotoxicity) Rank B OR Benzene/ Naphthalene sulfonic acids (Less
susceptible) Rank C OR Tamoxifen (Hepatotoxicity) Alert by Repeated dose
(HESS)
Domain
logical expression index: "t"
Referential
boundary: The
target chemical should be classified as Alkene AND Ammonium salt AND
Aromatic amine AND Aryl AND Sulfonic acid by Organic Functional groups
ONLY
Domain
logical expression index: "u"
Referential
boundary: The
target chemical should be classified as Alkene AND Ammonium salt AND
Aromatic amine AND Aryl AND Sulfonic acid by Organic Functional groups
ONLY
Domain
logical expression index: "v"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= -4.46
Domain
logical expression index: "w"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= -3.4
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 815.9 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- K2 data from prediction OECD QSAR toolbox 3.3
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 Methyl Blue; IUPAC;Disodium [[4-[bis[4-[(sulphonatophenyl) amino]phenyl] methylene]cyclohexa-2,5-dien-1-ylidene]amino]ben..(28983-56-4 ) 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 Disodium [[4-[bis[4-[(sulphonatophenyl) amino]phenyl] methylene]cyclohexa-2,5-dien-1-ylidene]amino]ben..(28983-56-4 ). The study assumed the use of male and female Wistar strain in Subchronic study. No significant alterations were noted at the dose level of 815.90mg/Kg bw/day. The predicted No Observed Adverse Effect Level (NOAEL) for compound Disodium [[4-[bis[4-[(sulphonatophenyl) amino]phenyl] methylene]cyclohexa-2,5-dien-1-ylidene]amino]ben..is considered to be 815.90mg/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 Sub-chronic toxicity study for Read across was performed by S. A. Clode et al.( Fd Chem. Toxic., 1987) to determine the oral toxic nature of Amaranth; IUPAC trisodium 3-hydroxy-4-[(4-sulfonato-1-naphthyl)diazenyl]naphthalene-2,7-disulfonate (915-67-3). The read across share high similarity in structure and log kow .Therefore, it is acceptable to derive information on mutation from the analogue substance. In acombined repeated dose & carcinogenicity,Wistar male and female rats were treated withAmaranth dye in the concentration of 47, 242 and 1260 mg/kg bw/day for male and 49, 246 and 1260 mg/kg bw/day for female orally in fed.No significant effect on survival of treated rats were observed as compared to control.Significant decrease in body weight in male rats from week 4 to 73 and in female rat from 51 and 73 and increase in food consumption was observed in 1260 mg/kg bw/day treated rats as compared to control. Slight effect on body weight and food consumption was due to a reduction in the absorption or utilization of the nutrient. Average compound intake of male rats were 47, 242 and 1260 mg/kg bw/day and for female rats 49, 246 and 1260 mg/kg bw/day.Increase in water consumption was observed in 1260 mg/kg bw/day treated male rats as compared to control. Increased water loss was observed due to production of softer, moister faeces and a compensatory increase in water intake. Similarly, decreased in packed cell volume was observed at month 6 and 12 in male and at month 18 in female rats and slightly increased haemoglobin concentrations in female rats at termination of study and decrease in glutamic-oxalacetic transaminase activities in male and female rats but not significant in female rats were observed at 1260 mg/kg bw/day. Observed effect were not dose related or consistent between the sexes. Increase level of proteinin urine at 12 months in female was observed at 1260 mg/kg bw/day andSemi-quantitative analysis of urine for bilirubin and ketones was hindered at months 18 and 24 due to the contamination of the urine with amaranth which interfered with the colour reaction. Statistically significant increase in absolute and relative full and empty caecum weight were observed in male and female at 1260mg/kg bw/day andincrease in absolute and relative full caecum weight in male rats at 242mg/kg bw/day were observedas compared to control. The observed effect was not statistically significant as compared to control. In addition, Non-neoplastic transitional-cell hyperplasia of bladder, inflammatory cell infiltrate of the seminal vesicles and testicular interstitial-cell hyperplasia were observed in 47 mg/kg bw/day male and 1260 mg/kg bw/day treated male and female rats. Statistically significant increase in renal calcification and renal pelvic epithelial hyperplasia, lung oedema and haemorrhage, lymph-node haemorrhage and degenerative changes in the brain and nerve, degenerative and inflammatory changes in heart, inflammatory changes in thymus, aortic calcification and atrial thrombi were observed in 1260 mg/kg bw/day treated female rats. Statistically significant increase in neoplastic uterine polyps and vaginal fibromas were observed in 1260 mg/kg bw/day treated female rats. The observed effects were typical of this strain and occur in ageing rats. No effect on number of litters, number of pups per litter at day 18 and pup weight at day 18 were observed in treated rats as compared to control. Therefore, NOAEL was considered to be 1260 mg/kg body weight /day when Wistar male and female rats were treated with Amaranth dye orally in fed for 2 years.
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 Methyl Blue; IUPAC;Disodium [[4-[bis[4-[(sulphonatophenyl) amino]phenyl] methylene]cyclohexa-2,5-dien-1-ylidene]amino]ben..(28983-56-4 ) ,which is reported as 7.8526E-42 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 25 micron which is much larger size range compared to the inhalable particulate matter .Thus, exposure to inhalable dust, mist and vapour of the chemical Methyl Blue; IUPAC;Disodium [[4-[bis[4-[(sulphonatophenyl) amino]phenyl] methylene]cyclohexa-2,5-dien-1-ylidene]amino]ben..(28983-56-4 ) is highly unlikely. Therefore this study is considered for waiver.
Repeated dermal study;
The acute toxicity value for Methyl Blue; IUPAC;Disodium [[4-[bis[4-[(sulphonatophenyl) amino]phenyl] methylene]cyclohexa-2,5-dien-1-ylidene]amino]ben..(28983-56-4 ) (as provided in section 7.2.3) is 7167mg/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 Methyl Blue; IUPAC;Disodium [[4-[bis[4-[(sulphonatophenyl) amino]phenyl] methylene]cyclohexa-2,5-dien-1-ylidene]amino]ben.shall not exhibit 28 day repeated dose toxicity by the dermal route. In addition, there is no data available that suggests that Methyl Blue; IUPAC;Disodium [[4-[bis[4-[(sulphonatophenyl) amino]phenyl] methylene]cyclohexa-2,5-dien-1-ylidene]amino]ben.. 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, Methyl Blue; IUPAC;Disodium [[4-[bis[4-[(sulphonatophenyl) amino]phenyl] methylene]cyclohexa-2,5-dien-1-ylidene]amino]ben..(28983-56-4 )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, Methyl Blue; IUPAC;Disodium [[4-[bis[4-[(sulphonatophenyl) amino]phenyl] methylene]cyclohexa-2,5-dien-1-ylidene]amino]ben..(28983-56-4 )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.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.