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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
Key value for chemical safety assessment
Effects on fertility
Description of key information
The NOAEL was estimated to be 908 mg/kg bw when Wistar male and female rats were orally exposed with disodium [[4-[bis[4-[(sulphonatophenyl)amino]phenyl]methylene]cyclohexa-2,5-dien-1-ylidene]amino]benzenesulphonate.
Thus, as per criteria of CLP regulation, disodium [[4-[bis[4-[(sulphonatophenyl)amino]phenyl]methylene]cyclohexa-2,5-dien-1-ylidene]amino]benzenesulphonate can be not classified for reproductive toxicity.
Link to relevant study records
- Endpoint:
- toxicity to reproduction
- 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 the supporting QMRF report has been attached
- Qualifier:
- according to guideline
- Guideline:
- other: as below
- Principles of method if other than guideline:
- Prediction is done using QSAR Toolbox version 3.3
- GLP compliance:
- not specified
- Limit test:
- no
- Specific details on test material used for the study:
- - IUPAC Name: Disodium [[4-[bis[4-[(sulphonatophenyl)amino]phenyl]methylene]cyclohexa-2,5-dien-1-ylidene]amino]benzenesulphonate
- SMILES:O=S(=O)(c1ccccc1Nc1ccc(C(=C2C=CC(=N{+}c3ccccc3S(=O)(=O)O{-}.[Na]{+})C=C2)c2ccc(Nc3ccccc3S(=O)(=O)O{-})cc2)cc1)O{-}.[Na]{+}
- InChI: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
- Mol. formula: C37H26N3Na2O9S3
- Molecular Weight: 800.8182 g/mol - Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Route of administration:
- oral: feed
- Type of inhalation exposure (if applicable):
- not specified
- Vehicle:
- other: food
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- F0 and F1 generation: 75 days premating exposure; during mating and gestation until post natal day (PND) 21
- Frequency of treatment:
- Daily
- Details on study schedule:
- not specified
- Dose / conc.:
- 908 mg/kg bw/day
- No. of animals per sex per dose:
- 25
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- not specified
- Positive control:
- not specified
- Parental animals: Observations and examinations:
- not specified
- Oestrous cyclicity (parental animals):
- not specified
- Sperm parameters (parental animals):
- not specified
- Litter observations:
- not specified
- Postmortem examinations (parental animals):
- not specified
- Postmortem examinations (offspring):
- not specified
- Statistics:
- not specified
- Reproductive indices:
- not specified
- Offspring viability indices:
- not specified
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- 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
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Reproductive function: oestrous cycle:
- not specified
- Reproductive function: sperm measures:
- not specified
- Reproductive performance:
- not specified
- Dose descriptor:
- NOAEL
- Effect level:
- 908 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- reproductive performance
- Remarks on result:
- other: No effect observed
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality / viability:
- 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
- Sexual maturation:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not specified
- Histopathological findings:
- not specified
- Other effects:
- not specified
- Behaviour (functional findings):
- not specified
- Developmental immunotoxicity:
- not specified
- Dose descriptor:
- other: not specified
- Generation:
- other: not specified
- Based on:
- not specified
- Sex:
- not specified
- Basis for effect level:
- other: not specified
- Remarks on result:
- other: not specified
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Reproductive effects observed:
- not specified
- Treatment related:
- not specified
- Relation to other toxic effects:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Conclusions:
- The NOAEL was estimated to be 908 mg/kg bw when Wistar male and female rats were orally exposed with disodium [[4-[bis[4-[(sulphonatophenyl)amino]phenyl]methylene]cyclohexa-2,5-dien-1-ylidene]amino]benzenesulphonate.
- Executive summary:
In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the reproductive toxicity was estimated for disodium [[4-[bis[4-[(sulphonatophenyl)amino]phenyl]methylene]cyclohexa-2,5-dien-1-ylidene]amino]benzenesulphonate. The NOAEL was estimated to be 908 mg/kg bw when Wistar male and female rats were orally exposed with disodium [[4-[bis[4-[(sulphonatophenyl)amino]phenyl]methylene]cyclohexa-2,5-dien-1-ylidene]amino]benzenesulphonate.
Reference
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 "j" )
)
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 Non binder, MW>500 by Estrogen
Receptor Binding
Domain
logical expression index: "f"
Referential
boundary: The
target chemical should be classified as Non binder, without OH or NH2
group by Estrogen Receptor Binding
Domain
logical expression index: "g"
Referential
boundary: The
target chemical should be classified as Alkali Earth AND Non-Metals by
Groups of elements
Domain
logical expression index: "h"
Referential
boundary: The
target chemical should be classified as Transition Metals by Groups of
elements
Domain
logical expression index: "i"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= -9.56
Domain
logical expression index: "j"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 0.12
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 908 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- Data is Klimisch 2 and from OECD QSAR toolbox
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Additional information
Reproductive toxicity:
In different studies, disodium [[4-[bis[4-[(sulphonatophenyl)amino]phenyl]methylene]cyclohexa-2,5-dien-1-ylidene]amino]benzenesulphonate has been investigated for reproductive toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimation in rodents, i.e. most commonly in rats for disodium [[4-[bis[4-[(sulphonatophenyl)amino]phenyl]methylene]cyclohexa-2,5-dien-1-ylidene]amino]benzenesulphonate along with the study available on structurally similar read across substance Carmoisine (CAS no 3567-69-9).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 reproductive toxicity was estimated for disodium [[4-[bis[4-[(sulphonatophenyl)amino]phenyl]methylene]cyclohexa-2,5-dien-1-ylidene]amino]benzenesulphonate. The NOAEL was estimated to be 908 mg/kg bw when Wistar male and female rats were orally exposed with disodium [[4-[bis[4-[(sulphonatophenyl)amino]phenyl]methylene]cyclohexa-2,5-dien-1-ylidene]amino]benzenesulphonate.
In another study conducted by Fordet al(Food Chemical Toxicology. Vol. 25, No. 12, pp. 919-925, 1987) on structurally similar read across substanceCarmoisine (CAS no 3567-69-9), Wistar male and female rats were treated with Carmoisine in the concentration of 0 (control), 100, 400 or 1200 mg /kg body weight/day orally in feed for 115 weeks. No significant change of carmoisine on the condition or behaviour of the animals, apart from coloration of the fur, urine and faeces with an intensity increasing with dose. No effect on survival of treated rats was observed. No effect on mating, pregnancy, lactation and weaning of P treated rats as compared to control. In addition, Effect like coloration of the fur, urine and faeces with an intensity increasing with dose in F1 pups. But no significant change was observed in animals behaviour and condition in treated group compare to control. No significant change was observed in the survival of F1 treated group compare to control. Significant change was observed in the body weights of F1 males receiving 400 and 1200 mg/kg/day were lower than those of the controls throughout the study. Females receiving 1200 mg/kg/day weighed significantly less than the controls from week 32 onwards. In both sexes the magnitude of the observed differences increased with time. Significant change was observed in the food intakes of the1200 mg /kg/day males was observed compare to control. Even in female 1200 mg/kg/day were greater than those of the controls, but the differences in females was unrelated to dose. Water intakes of treated animals showed some inconsistency during the study. For the first 12 months there was a dose-related higher intake in both sexes receiving 400 or 1200 mg /kg/day. During the second year the water intake of males receiving 1200mg/kg/day or of females receiving 400 mg/ kg/day was no longer different from that of the controls. No significant change was observed at all dose level 100, 400 or 1200 mg /kg body weight/day of treated group compare to control. Lower glucose concentrations were observed in males at dose level of 1200 mg/kg/day compare to control. While a Lower glucose concentration was observed in females at dose level of 400 and 1200 mg/kg/day compare to control. Semi-quantitative analyses of urine were hindered in treated animals, particularly at the 1200 mg/kg/day, by the colour of the urine which obscured the colour reaction of the reagent test strips. Despite these limitations, which meant that some samples obtained from 1200 mg/kg/day animals were not usable, a higher proportion of samples from the 1200 mg/kg/day females showed a high level of protein at both 18 and 24 months. No significant change was observed in any organ except caecum weight. The caecum was the only organ whose weight and relative weight (g/100 g body weight) showed changes associated with treatment. At 1200 and 400 mg/kg/day dose level in males both weight and relative weight of the caecum, with and without contents, were greater than the control values, although the increases were only statistically significant at the1200 mg /kg body weight/day. In females at the dose level of 1200 mg /kg body weight/day only the relative weight of the empty caecum was significantly greater than that of the controls. The changes in caecum weight were accompanied by observations at autopsy that the caecum wall was thicker in the treated animals. Similarly, significant thickness was observed in caecum wall at 1200 mg /kg body weight/day group of treated animals compare to control. Age-related changes to be expected in rats of the strain used. Some of the changes recorded showed a positive dose-related trend together with a significantly higher incidence when individual groups were compared with the controls. These were pupillary hyperplasia of the bladder in males and blood/fibrin cysts of the adrenal gland and internal hyperplasia / medial hypertrophy of the pancreatic blood vessels in females. The total incidences of benign or malignant tumours showed no treatment-related differences. There were no differences between the treated and control groups in the incidences of individual types of tumour apart from adrenal phaeochromocytoma which showed a statistically significant treatment-related difference in males based on four tumours in the 1200 mg/kg/day group compare to controls. A similar difference was not observed in females. Therefore, NOAEL was considered to be 1200 mg/kg bw for P generation and 400 mg/kg bw for F1 generation when Wistar male and female rats were treated with Carmoisine orally in feed for 115 weeks.
Further supported by experimental study conducted by Holmeset al(Toxicology, 10 (1978) 169-183)on structurally similar read across substanceCarmoisine (CAS no 3567-69-9), Sprague-Dawley male and female rats were treated with Carmoisine in the concentration of 0,175, 400 and 1000 mg/kg bw orally in feed for 480 days. No significant changes in body weight and food consumption of P rats were observed as compared to control. Similarly, no effect on viability of F1a, F1b, F2a, F2b, F3a and F3b pups as compared to control. In addition, No effect on reproductive parameters such as Fertility index, Copulation index, Number of pups/litter at birth, Stillbirth incidence, Viability index of pups and Lactation index were observed in P, F1b and F2b rats as compared to control. Therefore, NOAEL was considered to be 1000 mg/kg bw for P, F1b and F2b generation when Sprague-Dawley male and female rats were treated with Carmoisine orally in feed for 480 days.
Thus, based on the above study and predictions on disodium [[4-[bis[4-[(sulphonatophenyl)amino]phenyl]methylene]cyclohexa-2,5-dien-1-ylidene]amino]benzenesulphonate and its read across substances, it can be concluded that NOAEL value is 908 mg/kg bw with no effect on reproduction. Thus, as per criteria of CLP regulation, disodium [[4-[bis[4-[(sulphonatophenyl)amino]phenyl]methylene]cyclohexa-2,5-dien-1-ylidene]amino]benzenesulphonate can be not classified for reproductive toxicity.
Effects on developmental toxicity
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Based on the above study and predictions on disodium [[4-[bis[4-[(sulphonatophenyl)amino]phenyl]methylene]cyclohexa-2,5-dien-1-ylidene]amino]benzenesulphonate and its read across substances, it can be concluded that NOAEL value is 908 mg/kg bw with no effect on reproduction. Thus, as per criteria of CLP regulation, disodium [[4-[bis[4-[(sulphonatophenyl)amino]phenyl]methylene]cyclohexa-2,5-dien-1-ylidene]amino]benzenesulphonate can be not classified for reproductive toxicity.
Additional information
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