Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 235-460-3 | CAS number: 12236-25-8
- 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
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 toxicity was predicted for 2-({4-[bis(2-hydroxyethyl)amino]-2- methylphenyl} diazenyl) -5-nitrobenzonitrile. The study assumed the use of male and female rats in a 24 months toxicity study. Since no significant treatment related effects were observed at the mentioned dose level, hence the No Observed Adverse Effect Level (NOAEL) for 2-({4-[bis(2-hydroxyethyl)amino]-2-methylphenyl}diazenyl)-5-nitrobenzonitrile is predicted to be 782.171447754 mg/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
- 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 from OECD QSAR Toolbox version 3.4 and the supporting QMRF report has been attached
- Qualifier:
- according to guideline
- Guideline:
- other: Refer below principle
- Principles of method if other than guideline:
- Prediction is done using OECD QSAR Toolbox version 3.4, 2018
- GLP compliance:
- not specified
- Limit test:
- no
- Specific details on test material used for the study:
- - Name of the test material: 2-({4-[bis(2-hydroxyethyl)amino]-2-methylphenyl}diazenyl)-5-nitrobenzonitrile
- IUPAC name: 2-({4-[bis(2-hydroxyethyl)amino]-2-methylphenyl}diazenyl)-5-nitrobenzonitrile
- Molecular formula: C18H19N5O4
- Molecular weight: 369.38 g/mole
- Substance type: Organic - Species:
- rat
- Strain:
- Wistar
- Details on species / strain selection:
- No data
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- No data
- Route of administration:
- oral: unspecified
- Details on route of administration:
- No data
- Vehicle:
- not specified
- Details on oral exposure:
- No data
- Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- No data
- Duration of treatment / exposure:
- 24 months
- Frequency of treatment:
- Daily
- Remarks:
- No data
- No. of animals per sex per dose:
- No data
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- No data
- Positive control:
- No data
- Observations and examinations performed and frequency:
- No data
- Sacrifice and pathology:
- No data
- Other examinations:
- No data
- Statistics:
- No data
- 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:
- No data
- Dose descriptor:
- NOAEL
- Effect level:
- 782.171 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No significant alterations were noted at the mentioned dose level
- Critical effects observed:
- not specified
- Conclusions:
- The No Observed Adverse Effect Level (NOAEL) for 2-({4-[bis(2-hydroxyethyl)amino]-2-methylphenyl}diazenyl)-5-nitrobenzonitrile is predicted to be 782.171447754 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 toxicity was predicted for 2-({4-[bis(2-hydroxyethyl)amino]-2- methylphenyl} diazenyl) -5-nitrobenzonitrile. The study assumed the use of male and female rats in a 24 months toxicity study. Since no significant treatment related effects were observed at the mentioned dose level, hence the No Observed Adverse Effect Level (NOAEL) for 2-({4-[bis(2-hydroxyethyl)amino]-2-methylphenyl}diazenyl)-5-nitrobenzonitrile is predicted to be 782.171447754 mg/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 7 nearest neighbours
Domain logical expression:Result: In Domain
(((((((("a"
or "b" )
and ("c"
and (
not "d")
)
)
and ("e"
and (
not "f")
)
)
and ("g"
and (
not "h")
)
)
and ("i"
and (
not "j")
)
)
and ("k"
and (
not "l")
)
)
and "m" )
and ("n"
and "o" )
)
Domain
logical expression index: "a"
Referential
boundary: The
target chemical should be classified as SN1 OR SN1 >> Nitrenium Ion
formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >>
Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion
formation >> Tertiary aromatic amine by DNA binding by OECD ONLY
Domain
logical expression index: "b"
Referential
boundary: The
target chemical should be classified as Radical OR Radical >> Radical
mechanism via ROS formation (indirect) OR Radical >> Radical mechanism
via ROS formation (indirect) >> Nitro Azoarenes OR SN1 OR SN1 >>
Nucleophilic attack after reduction and nitrenium ion formation OR SN1
>> Nucleophilic attack after reduction and nitrenium ion formation >>
Nitro Azoarenes by DNA binding by OASIS v.1.4 ONLY
Domain
logical expression index: "c"
Referential
boundary: The
target chemical should be classified as Not categorized by Repeated dose
(HESS)
Domain
logical expression index: "d"
Referential
boundary: The
target chemical should be classified as 4,4'-Diethylaminoethoxyhexestrol
(Hepatotoxicity) Alert OR Thiocarbamates/Sulfides (Hepatotoxicity) No
rank by Repeated dose (HESS)
Domain
logical expression index: "e"
Referential
boundary: The
target chemical should be classified as Non-Metals by Groups of elements
Domain
logical expression index: "f"
Referential
boundary: The
target chemical should be classified as Halogens by Groups of elements
Domain
logical expression index: "g"
Referential
boundary: The
target chemical should be classified as Non-Metals by Groups of elements
Domain
logical expression index: "h"
Referential
boundary: The
target chemical should be classified as Alkali Earth by Groups of
elements
Domain
logical expression index: "i"
Referential
boundary: The
target chemical should be classified as Non-Metals by Groups of elements
Domain
logical expression index: "j"
Referential
boundary: The
target chemical should be classified as Alkaline Earth by Groups of
elements
Domain
logical expression index: "k"
Referential
boundary: The
target chemical should be classified as Alcohol AND Alkyl arenes AND
Aromatic amine AND Aryl AND Azo AND Nitrile AND Nitrobenzene AND
Overlapping groups by Organic Functional groups (nested)
Domain
logical expression index: "l"
Referential
boundary: The
target chemical should be classified as Acetal by Organic Functional
groups (nested)
Domain
logical expression index: "m"
Similarity
boundary:Target:
Cc1cc(N(CCO)CCO)ccc1N=Nc1ccc(N(=O)=O)cc1C#N
Threshold=40%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization
Domain
logical expression index: "n"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= 0.492
Domain
logical expression index: "o"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 8.24
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 782 mg/kg bw/day
- Study duration:
- chronic
- Species:
- rat
- Quality of whole database:
- Data is from K2 prediction database
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
Prediction model based estimation and data from read across chemicals have been reviewed to determine the toxic nature of 2-({4-[bis(2-hydroxyethyl) amino]-2-methylphenyl} diazenyl) -5-nitrobenzonitrile. 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 toxicity was predicted for 2-({4-[bis(2-hydroxyethyl)amino]-2- methylphenyl} diazenyl) -5-nitrobenzonitrile. The study assumed the use of male and female rats in a 24 months toxicity study. Since no significant treatment related effects were observed at the mentioned dose level, hence the No Observed Adverse Effect Level (NOAEL) for 2-({4-[bis(2-hydroxyethyl)amino]-2-methylphenyl}diazenyl)-5-nitrobenzonitrile is predicted to be 782.171447754 mg/Kg bw/day.
The predicted data is further supported by the data from read across chemicals as mentioned below:
In the NTP report for 60 -70% structurally similar read across chemical, 14 days repeated dose oral toxicity study was performed to determine the toxic nature of HC Yellow 4 (RA CAS no. 59820 -43 -8; IUPAC name: 2-[2-(2-hydroxyethylamino)-5-nitrophenoxy]ethanol) using rats. The test chemical was mixed with feed and dosed to F344/N 5 male and 5 female rats at dose levels of 0, 500, 1000, 2000, 4000 or 8000 mg/Kg bw/day for 14 days. During the study period, the animals were observed for signs of toxicity, death, changes in body weight and feed consumption, and they were subjected to gross and histo-pathology. No deaths were observed and no signs of toxicity attributable to the test chemical administration were noted. The final mean body weights and mean body weight changes of males that received doses of 20,000 ppm (2000 mg/Kg bw/day) and above and females that received doses of10,000 ppm (1000 mg/Kg bw/day) and above were significantly lower than those of the controls. Feed consumption by males that received doses of 20,000 ppm (2000 mg/kg bw/day) or greater and females that received doses of 10,000 ppm (1000 mg/Kg bw/day) or greater was lower than that of the controls during the first week. During the second week, feed consumption by males in the 40,000 ppm (4000 mg/Kg bw/day) dose group was lower than controls; feed consumption by other male and female dose groups was similar to or higher than that of the controls. Because rats that received 40,000 ppm (4000 mg/Kg bw/day) did not gain weight, and the final mean body weights of rats that received 80,000 ppm (8000 mg/kg bw/day) were decreased approximately 30%, it was concluded that the feed consumption values were high and may have included feed scattered by animals searching for unadulterated feed. Significant changes in absolute and relative organ weights were observed but were considered to be secondary to decreases in body weights. Based on these observations made, No observed Adverse effect level (NOAEL) for male rats is considered to be 1000 mg/kg bw and female rats the NOAEL is considered to be 500 mg/Kg bw.
In another data available for the 50 -60% structurally similar read across chemical ( Commission Of The European Communities, 1988), 90 days repeated dose oral toxicity study was performed to determine the toxic nature of Pigment Red 3 (RA CAS no 2425 -85 -6; IUPAC name: 1-(4-Methyl- 2-nitrophenyl azo)-2- naphthol) using rats. The test chemical was mixed with feed and dosed to F344/N 5 male and 5 female rats at dose levels of 0, 125, 250, 500 or 1000 mg/Kg bw/day for 90 days. During the study period, the animals were observed for growth rate, death, hematological parameters and they were subjected to gross and histo-pathology. No deaths were observed and no signs of toxicity attributable to the test chemical administration were noted. No changes in hematological parameters were noted. Slight increases in liver weight were not clearly dose-related. Spleen weight was increased in males of the top-dose group. Microscopy of the six organs examined showed no relevant changes. Based on the observations made and since detailed data is not available, the No observed Adverse effect level (NOAEL) for male and female weanling rats is considered to be 1000 mg/kg bw /day.
Based on the data available for the target chemical and its read across, the test chemical is not likely to be a toxicant as per the criteria mentioned n CLP regulation.
Justification for classification or non-classification
Based on the data available for the target chemical and its read across, the test chemical (CAS no 12236 -25 -8) is not likely to be a toxicant as per the criteria mentioned n 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.