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EC number: 299-257-1 | CAS number: 93858-25-4
- 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
NOAEL was estimated to be 883 mg/kg bw when rats were orally exposed with 4-[(E)-2-(5-{[(2Z,4E)-6-chloro-4-[(3-sulfophenyl)imino]-1,2,3,4-tetrahydro-1,3,5-triazin-2-ylidene]amino}-2-sulfophenyl)diazen-1-yl]-5-oxo-1-(4-sulfophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid.
Thus, as per criteria of CLP regulation, 4-[(E)-2-(5-{[(2Z,4E)-6-chloro-4-[(3-sulfophenyl)imino]-1,2,3,4-tetrahydro-1,3,5-triazin-2-ylidene]amino}-2-sulfophenyl)diazen-1-yl]-5-oxo-1-(4-sulfophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid 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:
- Name:4-[(E)-2-(5-{[(2Z,4E)-6-chloro-4-[(3-sulfophenyl)imino]-1,2,3,4-tetrahydro-1,3,5-triazin-2-ylidene]amino}-2-sulfophenyl)diazen-1-yl]-5-oxo-1-(4-sulfophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid
SMILES:OC(=O)C1C(N=Nc2cc(Nc3nc(Nc4cccc(S(O)(=O)=O)c4)nc(Cl)n3)ccc2S(O)(=O)=O)C(=O)N(c2ccc(S(O)(=O)=O)cc2)N=1
InChI:1S/C25H18ClN9O12S3/c26-23-29-24(27-12-2-1-3-16(10-12)49(42,43)44)31-25(30-23)28-13-4-9-18(50(45,46)47)17(11-13)32-33-19-20(22(37)38)34-35(21(19)36)14-5-7-15(8-6-14)48(39,40)41/h1-11,19H,(H,37,38)(H,39,40,41)(H,42,43,44)(H,45,46,47)(H2,27,28,29,30,31)/b33-32+
Mol. formula: C25H18ClN9O12S3
Molecular Weight: 768.1192 g/mole - Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- not specified
- Route of administration:
- oral: gavage
- Type of inhalation exposure (if applicable):
- not specified
- Remarks on MMAD:
- not specified
- Vehicle:
- water
- Details on exposure:
- not specified
- Details on mating procedure:
- not specified
- Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- males treated 41 days (pre-mating, post-mating)
females treated 52 days (pre-mating, gestation, 4 days lactation) - Frequency of treatment:
- Daily
- Details on study schedule:
- not specified
- Dose / conc.:
- 883 mg/kg bw/day
- No. of animals per sex per dose:
- 10
- 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:
- 883 mg/kg bw/day (actual dose received)
- 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:
- NOAEL was estimated to be 883 mg/kg bw when rats were orally exposed with 4-[(E)-2-(5-{[(2Z,4E)-6-chloro-4-[(3-sulfophenyl)imino]-1,2,3,4-tetrahydro-1,3,5-triazin-2-ylidene]amino}-2-sulfophenyl)diazen-1-yl]-5-oxo-1-(4-sulfophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid.
- 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 4-[(E)-2-(5-{[(2Z,4E)-6-chloro-4-[(3-sulfophenyl)imino]-1,2,3,4-tetrahydro-1,3,5-triazin-2-ylidene]amino}-2-sulfophenyl)diazen-1-yl]-5-oxo-1-(4-sulfophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid. The NOAEL was estimated to be 883 mg/kg bw when rats were orally exposed with 4-[(E)-2-(5-{[(2Z,4E)-6-chloro-4-[(3-sulfophenyl)imino]-1,2,3,4-tetrahydro-1,3,5-triazin-2-ylidene]amino}-2-sulfophenyl)diazen-1-yl]-5-oxo-1-(4-sulfophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid.
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" or "e" )
and "f" )
and ("g"
and (
not "h")
)
)
and ("i"
and (
not "j")
)
)
and "k" )
and "l" )
and ("m"
and (
not "n")
)
)
and ("o"
and "p" )
)
Domain
logical expression index: "a"
Referential
boundary: The
target chemical should be classified as Substituted Triazines (Acute
toxicity) by US-EPA New Chemical Categories
Domain
logical expression index: "b"
Referential
boundary: The
target chemical should be classified as Acid moiety OR Amides OR
Hydrazines OR Triazines, Aromatic by Aquatic toxicity classification by
ECOSAR ONLY
Domain
logical expression index: "c"
Referential
boundary: The
target chemical should be classified as Acylation OR Acylation >> Direct
Acylation Involving a Leaving group OR Acylation >> Direct Acylation
Involving a Leaving group >> Acetates OR SN2 OR SN2 >> SN2 reaction at
sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl diazo
OR SNAr OR SNAr >> Nucleophilic aromatic substitution OR SNAr >>
Nucleophilic aromatic substitution >> Halo-triazines by Protein binding
by OECD ONLY
Domain
logical expression index: "d"
Referential
boundary: The
target chemical should be classified as Schiff base formation OR Schiff
base formation >> Pyrazolones and Pyrazolidinones derivatives OR Schiff
base formation >> Pyrazolones and Pyrazolidinones derivatives >>
Pyrazolones and Pyrazolidinones OR SNAr OR SNAr >> Nucleophilic
aromatic substitution on activated aryl and heteroaryl compounds OR SNAr
>> Nucleophilic aromatic substitution on activated aryl and heteroaryl
compounds >> Activated aryl and heteroaryl compounds by Protein binding
by OASIS v1.3 ONLY
Domain
logical expression index: "e"
Referential
boundary: The
target chemical should be classified as SN1 OR SN1 >> Nitrenium Ion
formation OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic
azo by DNA binding by OECD ONLY
Domain
logical expression index: "f"
Referential
boundary: The
target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion
formation AND SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic
azo by DNA binding by OECD ONLY
Domain
logical expression index: "g"
Referential
boundary: The
target chemical should be classified as Not known precedent reproductive
and developmental toxic potential by DART scheme v.1.0
Domain
logical expression index: "h"
Referential
boundary: The
target chemical should be classified as AhR binders.Polycyclic aromatic
hydrocarbons (PAHs) (3b-3) OR Alkyl amide, urea, thiourea, nitroso urea,
carbonate, guanidine and carbamate derivatives (21b1) OR Alkyl amide,
urea, thiourea, nitroso urea, carbonate, guanidine and carbamate
derivatives (21b1) >> Alkylamide or thioamide analogs OR Known precedent
reproductive and developmental toxic potential OR NO2-alkyl/NO2-benzene
derivatives (8b) OR Polyhalogenated benzene derivatives (8c) OR Toluene
and small alkyl toluene derivatives (8a) by DART scheme v.1.0
Domain
logical expression index: "i"
Referential
boundary: The
target chemical should be classified as Halogens AND Non-Metals by
Groups of elements
Domain
logical expression index: "j"
Referential
boundary: The
target chemical should be classified as Alkali Earth OR Metalloids by
Groups of elements
Domain
logical expression index: "k"
Referential
boundary: The
target chemical should be classified as Aromatic amine AND Aromatic
heterocyclic halide AND Aryl AND Aryl halide AND Azo AND Carboxylic acid
AND Pyrazolone AND Sulfonic acid AND Triazine AND Unsaturated
heterocyclic amine AND Unsaturated heterocyclic fragment by Organic
Functional groups ONLY
Domain
logical expression index: "l"
Similarity
boundary:Target:
OC(=O)C1C(N=Nc2cc(Nc3nc(Nc4cccc(S(O)(=O)=O)c4)nc(Cl)n3)ccc2S(O)(=O)=O)C(=O)N(c2ccc(S(O)(=O)=O)cc2)N=1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization
Domain
logical expression index: "m"
Referential
boundary: The
target chemical should be classified as Aromatic compound AND Carbonic
acid derivative AND Carboxylic acid derivative AND Halogen derivative
AND Heterocyclic compound AND Sulfonic acid AND Sulfonic acid derivative
by Organic functional groups, Norbert Haider (checkmol)
Domain
logical expression index: "n"
Referential
boundary: The
target chemical should be classified as Alkylarylether by Organic
functional groups, Norbert Haider (checkmol)
Domain
logical expression index: "o"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= -1.92
Domain
logical expression index: "p"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 8.85
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 883 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: Oral
In different studies, 4-[(E)-2-(5-{[(2Z,4E)-6-chloro-4-[(3-sulfophenyl)imino]-1,2,3,4-tetrahydro-1,3,5-triazin-2-ylidene]amino}-2-sulfophenyl)diazen-1-yl]-5-oxo-1-(4-sulfophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid has been investigated for reproductive toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimated data in rodents, i.e. most commonly in rats for 4-[(E)-2-(5-{[(2Z,4E)-6-chloro-4-[(3-sulfophenyl)imino]-1,2,3,4-tetrahydro-1,3,5-triazin-2-ylidene]amino}-2-sulfophenyl)diazen-1-yl]-5-oxo-1-(4-sulfophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid along with the study available on structurally similar read across substance Pigment Orange 13 (CAS no 93858-25-4) and 3-carboxy-5-hydroxy-1-(4'- sulphophenyl)-4-(4'-sulphophenylazo) pyrazole trisodium salt (CAS no 1934-21-0). The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.
In a prediction done by SSS (2018) using the OECD QSAR toolbox with log kow as the primary descriptor, the reproductive toxicity was estimated for 4-[(E)-2-(5-{[(2Z,4E)-6-chloro-4-[(3-sulfophenyl)imino]-1,2,3,4-tetrahydro-1,3,5-triazin-2-ylidene]amino}-2-sulfophenyl)diazen-1-yl]-5-oxo-1-(4-sulfophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid. The NOAEL was estimated to be 883 mg/kg bw when rats were orally exposed with 4-[(E)-2-(5-{[(2Z,4E)-6-chloro-4-[(3-sulfophenyl)imino]-1,2,3,4-tetrahydro-1,3,5-triazin-2-ylidene]amino}-2-sulfophenyl)diazen-1-yl]-5-oxo-1-(4-sulfophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid.
In another study conducted by J-CHECK (Hazard-Data Evaluation Committee of National Institute of Technology and Evaluation based on the GLP study report obtained by Japanese Ministry of Economy, Trade and Industry. Ministry of Economy, Trade and Industry, Japan, 2010) on structurally similar read across substance Pigment Orange 13 (CAS no 93858-25-4), Crl:CD (SD) male and female rats were treated with Pigment Orange 13 in the concentration of 0, 40, 200, 1000 mg/kg bw/day orally by gavage for 41 - 47 days (from 14 days before mating to day 4 of lactation. No mortality, Clinical signs, behavior modification, change in Body weight and Food consumption of treated rats were observed as compared to control. Similarly, No significant effect on Urinalysis, Hematology, Blood chemistry, Organ weight and Histopathology of treated rat were observed as compared to control rats. In addition, no effect on reproductive parameters of treated rats were observed such as estrous cycle, number of corpora lutea or implantations, Copulation index, fertility index, or pairing days until copulation and delivery index of treated rat as compared to control. No effect on organ weight and histopathological changes were observed in treated male and female rats as compared to control. No effect on viability of pups and body weight were observed on day 0 and 4 as compared to control. No external and histopathological abnormality and were observed in pups as compared to control. Therefore, NOAEL was considered to be 1000 mg/kg bw for P and F1 generation when Crl:CD (SD) male and female rats were treated with Pigment Orange 13 orally by gavage for 47 days.
Further supported by experimental study given by European Food Safety Authority (EFSA) (EFSA Journal 2009; 7(11):1331) on structurally similar read across substance 3-carboxy-5-hydroxy-1-(4'- sulphophenyl)-4-(4'-sulphophenylazo) pyrazole trisodium salt (CAS no 1934-21-0), Osborne-Mendel female rat were treated with 3-carboxy-5-hydroxy-1-(4'- sulphophenyl)-4-(4'-sulphophenylazo) pyrazole trisodium salt in the concentration of 0, 60, 100, 200, 400, 600, or 1000 mg/kg bw/day orally by gavage for 19 days. Number and type of implantations were observed in treated rats. Similarly, No effects on fetal viability, gross pathology, fetal skeletal and visceral development were observed as compared to control. Therefore, NOAEL was considered to be 1000 mg/kg/day for P and F1 generation when Osborne-Mendel female rats treated with 3-carboxy-5-hydroxy-1-(4'- sulphophenyl)-4-(4'-sulphophenylazo) pyrazole trisodium salt orally by gavage for 19 days.
Again supported by experimental study given by European Food Safety Authority (EFSA) (EFSA Journal 2009; 7(11):1331) on structurally similar read across substance 3-carboxy-5-hydroxy-1-(4'- sulphophenyl)-4-(4'-sulphophenylazo) pyrazole trisodium salt (CAS no 1934-21-0), Osborne-Mendel female rat were treated with 3-carboxy-5-hydroxy-1-(4'- sulphophenyl)-4-(4'-sulphophenylazo) pyrazole trisodium salt in the concentration of 0, 67, 132, 292, 568, and 1064 mg/kg bw/day orally in drinking water throughout gestation. No effect on clinical sign, Number and type of implantations and fetal size (weight and length) were observed in treated rats. Similarly, No effects on fetal viability, gross pathology, fetal skeletal and visceral development were observed as compared to control. Therefore, NOAEL was considered to be 1000 mg/kg/day for P and F1 generation when Osborne-Mendel female rats treated with 3-carboxy-5-hydroxy-1-(4'- sulphophenyl)-4-(4'-sulphophenylazo) pyrazole trisodium salt orally by gavage for 19 days.
Thus, based on the above study and predictions on 4-[(E)-2-(5-{[(2Z,4E)-6-chloro-4-[(3-sulfophenyl)imino]-1,2,3,4-tetrahydro-1,3,5-triazin-2-ylidene]amino}-2-sulfophenyl)diazen-1-yl]-5-oxo-1-(4-sulfophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid and its read across substances, it can be concluded that NOAEL value is 883 mg/kg bw with no effect on reproduction. Thus, as per criteria of CLP regulation, 4-[(E)-2-(5-{[(2Z,4E)-6-chloro-4-[(3-sulfophenyl)imino]-1,2,3,4-tetrahydro-1,3,5-triazin-2-ylidene]amino}-2-sulfophenyl)diazen-1-yl]-5-oxo-1-(4-sulfophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid 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
Thus, based on the above study and predictions on 4-[(E)-2-(5-{[(2Z,4E)-6-chloro-4-[(3-sulfophenyl)imino]-1,2,3,4-tetrahydro-1,3,5-triazin-2-ylidene]amino}-2-sulfophenyl)diazen-1-yl]-5-oxo-1-(4-sulfophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid and its read across substances, it can be concluded that NOAEL value is 883 mg/kg bw with no effect on reproduction.
Additional information
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