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EC number: 252-652-2 | CAS number: 35642-64-9
- 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
The repeated dose toxicity study was predicted using OECD QSAR toolbox version 3.4 (2017) with log kow as the primary descriptor and considering the four closest read across substances; to evaluate the toxic effects of administration of 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6- chloro-1,3,5-triazin-2-yl)amino] phenyl]azo]naphthalene-1,3,6-trisulphonic acid (CAS No. 35642-64-9) in rats by the oral route in a 13 weeks of exposure. No adverse effects were observed. Therefore, the no-observed adverse effect level (NOAEL) of 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl] azo]naphthalene- 1,3,6-trisulphonic acid (CAS No. 35642-64-9) was estimated to be 681.29 mg/kg bw/day (actual dose received).
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- sub-chronic 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 3.4 and the supporting QMRF report has been attached.
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- Prediction is done using OECD QSAR Toolbox version 3.4 with respect to the descriptor log Kow.
- GLP compliance:
- not specified
- Specific details on test material used for the study:
- Name of the test chemical: 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid
Molecular formula: C20H16ClN9O10S3
Molecular weight: 674.0504 g/mol
Smiles Notation: S(=O)(=O)(c1c(/N=N/c2c(NC(=O)N)cc(Nc3nc(nc(n3)Cl)N)cc2)cc2c(S(=O)(=O)O)cc(S(=O)(=O)O)cc2c1)O
InChI: 1S/C20H16ClN9O10S3/c21-17-26-18(22)28-20(27-17)24-9-1-2-12(13(5-9)25-19(23)31)29-30-14-7-11-8(4-16(14)43(38,39)40) 3-10(41(32,33)34)6-15(11)42(35,36)37/h1-7H,(H3,23,25,31)(H,32,33,34)(H,35,36,37)(H,38,39,40)(H3,22,24,26,27,28)/b30-29+
Substance Type: Organic
Physical State: solid - Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Route of administration:
- oral: gavage
- Vehicle:
- not specified
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- Daily
- Dose / conc.:
- 681.29 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 10 male and 10 female rats
- Control animals:
- not specified
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule:Not specified
- Cage side observations checked in table [No.?] were included.: Mortality was observed.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule:No data
BODY WEIGHT: Yes
- Time schedule for examinations:No data
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Not specified
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Not specified
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Not specified
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Not specified
- Time schedule for examinations:Not specified
OPHTHALMOSCOPIC EXAMINATION: Not specified
- Time schedule for examinations:Not specified
- Dose groups that were examined:Not specified
HAEMATOLOGY: Not specified
- Time schedule for collection of blood:Not specified
- Anaesthetic used for blood collection: Not specified
- Animals fasted: Not specified
- How many animals:Not specified
- Parameters checked in table [No.?] were examined.Not specified
CLINICAL CHEMISTRY: Not specified
- Time schedule for collection of blood:Not specified
- Animals fasted:Not specified
- How many animals:Not specified
- Parameters checked in table [No.?] were examined.Not specified
URINALYSIS: Not specified
- Time schedule for collection of urine:Not specified
- Metabolism cages used for collection of urine: Not specified
- Animals fasted: Not specified
- Parameters checked in table [No.?] were examined.Not specified
NEUROBEHAVIOURAL EXAMINATION: Not specified
- Time schedule for examinations: Not specified
- Dose groups that were examined: Not specified
- Battery of functions tested: sensory activity / grip strength / motor activity / other: Not specified
IMMUNOLOGY: Not specified
- Time schedule for examinations:Not specified
- How many animals:Not specified
- Dose groups that were examined:Not specified
- Parameters checked in table [No.?] were examined.Not specified - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes - Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- 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:
- no effects observed
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Dose descriptor:
- NOAEL
- Effect level:
- 681.29 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- clinical signs
- gross pathology
- histopathology: non-neoplastic
- mortality
- other: No effects observed.
- Critical effects observed:
- no
- Conclusions:
- The no-observed adverse effect level (NOAEL) of 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene- 1,3,6-trisulphonic acid (CAS No. 35642-64-9) was estimated to be 681.29 mg/kg bw/day (actual dose received).
- Executive summary:
The repeated dose toxicity study was predicted using OECD QSAR toolbox version 3.4 (2017) with log kow as the primary descriptor and considering the four closest read across substances; to evaluate the toxic effects of administration of 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6- chloro-1,3,5-triazin-2-yl)amino] phenyl]azo]naphthalene-1,3,6-trisulphonic acid (CAS No. 35642-64-9) in rats by the oral route in a 13 weeks of exposure. No adverse effects were observed. Therefore, the no-observed adverse effect level (NOAEL) of 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl] azo]naphthalene- 1,3,6-trisulphonic acid (CAS No. 35642-64-9) was estimated to be 681.29 mg/kg bw/day (actual dose received).
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" )
and "c" )
and "d" )
and ("e"
and "f" )
)
Domain
logical expression index: "a"
Referential
boundary: The
target chemical should be classified as Acid moiety OR Anilines
(Unhindered) OR Substituted Ureas OR Triazines, Aromatic by Aquatic
toxicity classification by ECOSAR ONLY
Domain
logical expression index: "b"
Referential
boundary: The
target chemical should be classified as Activated N-heterocycles by Skin
irritation/corrosion Inclusion rules by BfR
Domain
logical expression index: "c"
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: "d"
Referential
boundary: The
target chemical should be classified as Not bioavailable by Lipinski
Rule Oasis ONLY
Domain
logical expression index: "e"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= -1.93
Domain
logical expression index: "f"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 6.5
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 681.29 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- The data is Klimicsh 2 and from OECD QSAR toolbox version 3.4 (2017).
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: oral
Various repeated dose toxicity studies has been investigated to observe the adverse general toxicological effects occurring as a result of repeated daily dosing with, or exposure, to a substance for a specified period up to the expected lifespan of the test species. Often are the studies based on
experiments and estimated data in rodents for 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3, 6-trisulphonic acid along with the study available on structurally similar read across substances Red 2G (CAS No.- 3734-67-6), disodium 3-[(2,4-dimethyl-5- sulp honatophenyl)azo]-4-hydroxynaphthalene-1-sulphonate (CAS No. 4548-53-2) and FD & C RED NO. 40 (CAS No. 25956-17-6). The predicted data using the OECD QSAR toolbox has also been compared with the experimental data. The studies are summarized as below:
The repeated dose toxicity study was predicted using OECD QSAR toolbox version 3.4 (2017) with log kow as the primary descriptor and considering the four closest read across substances; to evaluate the toxic effects of administration of 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6- chloro-1,3,5-triazin-2-yl)amino] phenyl]azo]naphthalene-1,3,6-trisulphonic acid (CAS No. 35642-64-9) in rats by the oral route in a 13 weeks of exposure. No adverse effects were observed. Therefore, the no-observed adverse effect level (NOAEL) of 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl] azo]naph thalene- 1,3,6-trisulphonic acid (CAS No. 35642-64-9) was estimated to be 681.29 mg/kg bw/day (actual dose received).
Also, the subchronic repeated dose toxicity study on structurally similar read across substance Red 2G (CAS No.- 3734-67-6) in mice was published in an European Food Safety AuthorityJournal (The EFSA Journal (2007) 515, 1-28). Five groups of 15 male and 15 female mice were given diets containing 0, 0.01, 0.1, 1, or 2% Red 2G (equivalent to 14, 143, 1429, or 2858 mg/kg bw) for three months. 5 animals per group were haematologically investigated and fully autopsied at days 26, 55, and 96. A dose- dependent increase in the incidence of Heinz bodies was observed. Splenomegaly was observed in both sexes at 2% and in females at 1%. Relative liver weig hts were increased in females at 1% and 2% at day 26, and at 2% at days 55 and 96. Haemosiderin was increased in the liver (Kupffer cells) at 1% and 2%. In the spleen haemosiderin was increased at 2% at all test days, and at the other concentrations increased with treatment and duration. No adverse effects on growth or food consumption were evident. Thus under the condition of the study, the no-observed adverse effect level (NOAEL) of Red 2G (CAS No.- 3734-67-6) in this subchronic study in mice was observed to be 143.0 mg/kg bw.
In addition to these studies, the chronic repeated dose toxicity study was performed by K. J. Davis et al., (Toxicology And Applied Pharamacology 8, 306-317 (1966)) on Osborne-Mendel rats (Five groups of 24 litter mated). Total 120 rats were used from which 16 were discarded because of advanced postmortem autolysis and 104 were received in the pathology laboratory for gross and microscopic examination.Six male and six female rats, evenly divided between control animals and those fed Disodium 3-[(2,4-dimethyl-5- sulp honatophenyl)azo]-4-hydroxynaphthalene-1-sulphonate (Ponceau SX) at 5%, were examined in detail. Of the 12 animals, examinations were made of urinary bladder of 11 animals, prostate of 6, and parathyroid of 6. Liver, kidney, any tumors present, and testis in males were examined in all the remaining 92 rats. Gross lesions most commonly seen were tumors and granular kidneys but none was related to Ponceau SX treatment. No microscopic pathologic changes were attributed to Ponceau SX. No microscopic pathologic changes were attributed to Ponceau SX. No effect on survival, haematology and organ weight was observed. Therefore, The NOAEL was considered to be 5% (2500 mg/kg bw/day) when Osborne-Mendel female rats were treated wtih Disodium 3-[(2, 4-dim ethyl-5 -sulp honatophenyl)azo]-4-hydroxynaphthalene-1-sulphonate (Ponceau SX) (CAS No. 4548-53-2) orally.
Moreover, in the study conducted by T. F. X. Collins et al. (Food and cosmatics toxicology, Vol. 18. pp 561 to 568, 1980), Osborne-Mendelfemale rats were treated wtih FD & C RED NO. 40 in the concentration of 0, 7.5, 15, 30, 100 and 200 mg/kg body weight /day in distilled water by oral gavage. No external signs of toxicity and animals were appeared healthy and behaved normally in treated groups as compared to control.No effects on weight gain and water consumption were observed in treated female rats as compared to control. No significant effect on numbers of corpora lutea, implantations, early and late deaths and viable foetuses per litter or on the percentage of preimplantation loss were observed in treated group as compared to control. Slightly increase in percentage of early resorptions were observed in 7.5 and 15 mg/kg bw/day but this response were appeared to be the result of sporadic occurrences. One litter was totally resorbed at 100 mg/kg bw/day. But, the percentage of females with more than one and with more than two resorptions showed no dose-related correlation as comapred to control. In addition, no effect on live or dead foetuses and mean foetal body weight and percentage of males and females per treatment group were observed as compared to control. Increased in number of runts were observed at 7.5, 15, 100 and 200 mg/kg bw/day treated dams, No compound-related external variations were observed in litters of treated dams as compared to control. Slightly decrease in males and females Crown-rump length were observed but were not significantly significant with increasing dose level. No effect on percentage of males and females per treatment group were observed as compared to control. Therefore, NOAEL was considered to be 200 mg/kg body weight /day when Osborne-Mendel female rats were treated wtih FD & C RED NO. 40 orally by gavage for 19 days.
On the basis of evidence from above studies (target substance and to its read across substances) in experimental animals, it can be presumed that there is no potential to be harmful to human health following repeated exposure. The substance 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin -2-yl) amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid (CAS No. 35642-64-9) is unclassified because no specific target organ toxicity was seen. Thus, on the basis of CLP classification criteria the substance is not classified.
Repeated dose toxicity: inhalation
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 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]napht halene- 1,3,6 -trisulphonic acid, which is reported as 3.72E-033 Pa. Also considering the particle size distribution of the substance the majority of the particles were found to be in the size of 103.0 micrometer which is much larger size range compared to the inhalable particulate matter. Thus, exposure to inhalable dust, mist and vapour of the chemical 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid is highly unlikely. Therefore this study is considered for waiver.
Repeated dose toxicity: dermal
The acute toxicity value for 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid (as provided in section 7.2.3) is >2000 mg/kg body weight. The substance was also found to be not irrtating to skin. Also, given the use of the chemical as reactive dye; repeated exposure by the dermal route is unlikely. Thus, it is expected that 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5- triazin-2-yl) amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid shall not exhibit 28 day repeated dose toxicity by the dermal route. In addition, there is no dermal absorption data as well as no data available that suggests that 7-[[2-[(aminocarbo nyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo] naphthalene-1,3,6 -trisulphonic acid shall exhibit repeated dose toxicity by the dermal route. Hence this end point was considered for waiver.
Justification for classification or non-classification
Based on the available data for the assessment of repeated dose toxicity by oral, inhalation and dermal route and following CLP Regulation (EC) No 1272/2008, the substance 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid is not classified.
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