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EC number: 257-848-1 | CAS number: 52320-66-8
- 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
The skin sensitization potential of target chemical 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8) was assessedin various experimental studies which were conducted on guinea pigs and humans for target chemical2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8) andits structurally similar read across substancesC. I. Pigment Yellow 12 (CAS no: 6358-85-6) and C. I. Pigment Yellow 13 (CAS no: 5102-83-0). The predicted data usingQSAR toolboxhas also been compared with the experimental data.Based on the available data for the target and read across substances and applying the weight of evidence approach, it can be concluded that chemical 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8) is unable to cause skin sensitization and thus can be considered as not sensitizing. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- 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 3.3 and QMRF report has been attached
- Qualifier:
- according to guideline
- Guideline:
- other: estimated data
- Principles of method if other than guideline:
- Prediction is done using QSAR Toolbox version 3.3
- GLP compliance:
- not specified
- Type of study:
- guinea pig maximisation test
- Justification for non-LLNA method:
- not specified
- Specific details on test material used for the study:
- - Name of test material (IUPAC name): 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide
- Molecular formula: C18H17ClN4O5
- Molecular weight: 404.808 g/mol
- Smiles notation: O=C(Nc1ccc(OCC)cc1)[C@@H](\N=N\c1c([N+](=O)[O-])cc(cc1)Cl)C(=O)C
- InChl: 1S/C18H17ClN4O5/c1-3-28-14-7-5-13(6-8-14)20-18(25)17(11(2)24)22-21-15-9-4-12(19)10-16(15)23(26)27/h4-10,17H,3H2,1-2H3,(H,20,25)/b22-21+
- Substance type: Organic
- Physical state: Solid - Species:
- guinea pig
- Strain:
- Dunkin-Hartley
- Sex:
- not specified
- Details on test animals and environmental conditions:
- No data available
- Route:
- intradermal and epicutaneous
- Vehicle:
- not specified
- Concentration / amount:
- No data available
- Day(s)/duration:
- No data available
- Adequacy of induction:
- not specified
- No.:
- #1
- Route:
- epicutaneous, occlusive
- Vehicle:
- not specified
- Concentration / amount:
- No data available
- Day(s)/duration:
- 48 hours
- Adequacy of challenge:
- not specified
- No. of animals per dose:
- 20
- Details on study design:
- No data available
- Reading:
- 1st reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- No data available
- No. with + reactions:
- 0
- Total no. in group:
- 20
- Clinical observations:
- No skin sensitization was observed in treated guinea pigs.
- Remarks on result:
- no indication of skin sensitisation
- Cellular proliferation data / Observations:
- No skin sensitization was observed in treated guinea pigs.
- Interpretation of results:
- other: Not sensitizing
- Conclusions:
- The chemical 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8) was estimated to be not sensitizing to the skin of Dunkin-Hartley guinea pigs. Based on the estimated result 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8) failed to induce skin sanitization effects and hence is considered to be not sensitizing to Dunkin-Hartley guinea pigs.
- Executive summary:
The skin sensitization potential of 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8) was estimated using OECD QSAR toolbox version 3.4 with log Pow as the primary descriptor. The chemical 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8) was estimated to be not sensitizing to the skin of Dunkin-Hartley guinea pigs. Based on the estimated result 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8) failed to induce skin sanitization effects and hence is considered to be not sensitizing to Dunkin-Hartley guinea pigs and can be classified under the category ˋ Not Classified’ as per CLP regulation.
Reference
The
prediction was based on dataset comprised from the following
descriptors: "Skin Sensitisation"
Estimation method: Takes highest mode value from the 9 nearest neighbours
Domain logical expression:Result: In Domain
((((((((("a"
and ("b"
and (
not "c")
)
)
and ("d"
and (
not "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 Amides by Aquatic toxicity
classification by ECOSAR
Domain
logical expression index: "b"
Referential
boundary: The
target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion
formation AND SN1 >> Nitrenium Ion formation >> Aromatic azo AND SN1 >>
Nitrenium Ion formation >> Aromatic nitro by DNA binding by OECD
Domain
logical expression index: "c"
Referential
boundary: The
target chemical should be classified as Acylation OR Acylation >> Direct
Addition of an Acyl Halide OR Acylation >> Direct Addition of an Acyl
Halide >> Acyl halide OR Acylation >> P450 Mediated Activation to
Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation
to Isocyanates or Isothiocyanates >> Formamides OR 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 >> Alkyl phenols 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 >> Hydroquinones OR Michael addition
>> Polarised Alkenes-Michael addition OR Michael addition >> Polarised
Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR No alert
found OR Schiff base formers OR Schiff base formers >> Chemicals
Activated by P450 to Glyoxal OR Schiff base formers >> Chemicals
Activated by P450 to Glyoxal >> Ethylenediamines (including piperazine)
OR SN1 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >>
Hydrazine OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion
Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation
>> Aromatic phenylureas OR SN1 >> Nitrenium Ion formation >> Primary
(unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >>
Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary
aromatic amine OR SN1 >> Nitrenium Ion formation >> Unsaturated
heterocyclic azo OR SN2 OR SN2 >> SN2 at an sp3 Carbon atom OR SN2 >>
SN2 at an sp3 Carbon atom >> Phosphates by DNA binding by OECD
Domain
logical expression index: "d"
Referential
boundary: The
target chemical should be classified as Acylation AND Acylation >> Ester
aminolysis AND Acylation >> Ester aminolysis >> Amides by Protein
binding by OASIS v1.3
Domain
logical expression index: "e"
Referential
boundary: The
target chemical should be classified as Nucleophilic addition OR
Nucleophilic addition >> Addition to carbon-hetero double bonds OR
Nucleophilic addition >> Addition to carbon-hetero double bonds >>
Ketones by Protein binding by OASIS v1.3
Domain
logical expression index: "f"
Referential
boundary: The
target chemical should be classified as Has superfragment AND
O=C(R{*})C(C(=O)NR{*})N=NR{*} by Superfragments ONLY
Domain
logical expression index: "g"
Referential
boundary: The
target chemical should be classified as (!Undefined)Group All Lipid
Solubility < 0.01 g/kg AND (!Undefined)Group CNHal Lipid Solubility < 4
g/kg AND (!Undefined)Group CNHal Lipid Solubility < 400 g/kg AND Group
All Melting Point > 200 C AND Group CNHal Aqueous Solubility < 0.001 g/L
AND Group CNHal Aqueous Solubility < 0.1 g/L AND Group CNHal log Kow >
3.8 AND Group CNHal Molecular Weight > 370 g/mol AND Group CNHal
Molecular Weight > 380 g/mol by Skin irritation/corrosion Exclusion
rules by BfR
Domain
logical expression index: "h"
Referential
boundary: The
target chemical should be classified as (!Undefined)Group CN Lipid
Solubility < 0.4 g/kg OR Group All log Kow > 9 OR Group CN Aqueous
Solubility < 0.0001 g/L OR Group CN Aqueous Solubility < 0.1 g/L OR
Group CN log Kow > 4.5 OR Group CN Melting Point > 180 C OR Group CN
Molecular Weight > 290 g/mol OR Group CN Molecular Weight > 540 g/mol OR
Group CN Vapour Pressure < 0.001 Pa by Skin irritation/corrosion
Exclusion rules by BfR
Domain
logical expression index: "i"
Referential
boundary: The
target chemical should be classified as Group 14 - Carbon C AND Group 15
- Nitrogen N AND Group 16 - Oxygen O AND Group 17 - Halogens Cl AND
Group 17 - Halogens F,Cl,Br,I,At by Chemical elements
Domain
logical expression index: "j"
Referential
boundary: The
target chemical should be classified as Group 17 - Halogens F by
Chemical elements
Domain
logical expression index: "k"
Similarity
boundary:Target:
CCOc1ccc(NC(=O)C(C(C)=O)N=Nc2ccc(Cl)cc2N(=O)=O)cc1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization
Domain
logical expression index: "l"
Similarity
boundary:Target:
CCOc1ccc(NC(=O)C(C(C)=O)N=Nc2ccc(Cl)cc2N(=O)=O)cc1
Threshold=50%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization
Domain
logical expression index: "m"
Referential
boundary: The
target chemical should be classified as Alkylarylether AND Aromatic
compound AND Aryl chloride AND Aryl halide AND Carbonyl compound AND
Carboxylic acid amide AND Carboxylic acid sec. amide AND Ether AND
Halogen derivative AND Ketone AND Nitro compound by Organic functional
groups, Norbert Haider (checkmol)
Domain
logical expression index: "n"
Referential
boundary: The
target chemical should be classified as Carbonic acid derivative OR CO2
derivative (general) OR Heterocyclic compound 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 >= 3.55
Domain
logical expression index: "p"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 8.15
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not sensitising)
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
- Additional information:
Various studieshas been investigated for the test chemical2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8) to observe the potential for skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pigs and humans for target chemical2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8) and its structurally similar read across substancesC. I. Pigment Yellow 12 (CAS no: 6358-85-6) and C. I. Pigment Yellow 13 (CAS no: 5102-83-0). The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;
The skin sensitization potential of 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8) was estimated to be not sensitizing to the skin of Dunkin-Hartley guinea pigs. Based on the estimated result 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8) can be considered to be not sensitizing to Dunkin-Hartley guinea pigs.
The above result was further supported by the patch test studies conducted by Thierbach MA et.al., {Contact Dermatitis, 27, 22-26, (1992)} for two read across substances C. I. Pigment Yellow 12 (CAS no: 6358-85-6) and C. I. Pigment Yellow 13 (CAS no: 5102-83-0) as follow;
The patch test for both the chemical was performed in 32 patients with an established p-aminoazobenzene allergy (32 patients for each patch test). The test was conducted on a group of 32 patients with presumable allergic contact dermatitis and all with a positive patch teat reaction to p-aminoazobenzene (0.25% pet). The group consisted of 20 women (mean age 39.9 years) and men (mean age 46.6 years). 11 patients had previously also shown sensitization to PPD (Para-phenyldiamine). 30 patients with an allergic contact dermatitis but negative to p-aminoazobenzene and PPD were also tested with the same patch test series. A patch with test chemical was placed in small squares (about 1.0 cm2) and wetted with 1 drop of tap water, water was used to imitate the circumstances (wet hands or sweating of hands). By this procedure a slight but visible yellow stain on the skin was found at the test site after 2 days of application, indicating liberation of the dyes. The chemicals did not elicit a positive patch test reaction in any one of the 32 patients’ positive to p-aminoazobenzene nor in the 30 control subjects. Hence the chemicals C. I. Pigment Yellow 12 (CAS no: 6358-85-6) and C. I. Pigment Yellow 13 (CAS no: 5102-83-0) were considered to be not sensitizing.
Thus on the basis of available data for thetarget chemical2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8) and its structurally similar read across substancesC. I. Pigment Yellow 12 (CAS no: 6358-85-6) and C. I. Pigment Yellow 13 (CAS no: 5102-83-0),it can be concluded thatchemical 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8) is unable to cause skin sensitization and considered as non-skin sensitizer. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.
Justification for classification or non-classification
The skin sensitization potential of test substance 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8) and its structurally similar read across substances C. I. Pigment Yellow 12 (CAS no: 6358-85-6) and C. I. Pigment Yellow 13 (CAS no: 5102-83-0) were observed in various studies. From the results obtained from these studies it is concluded that the chemical 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8) is not likely to cause skin sensitization and hence can be classified as non-skin sensitizer.
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