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EC number: 261-867-0 | CAS number: 59703-00-3
- 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 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride(59703-00-3) was estimated by using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride (59703-00-3) was predicted to be not sensitizing to the skin of female and male Hartley guinea pig.
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Remarks:
- in vivo
- 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 the QMRF report has been attached
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- Principles of method if other than guideline:
- Prediction is done by using OECD QSAR toolboxv.3.3
- GLP compliance:
- not specified
- Type of study:
- Buehler test
- Justification for non-LLNA method:
- Not specified.
- Specific details on test material used for the study:
- - Name of test material (as cited in study report): 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride
- Molecular formula: C7H9ClN2O3
- Molecular weight: 204.612 g/mol
- Substance type: Organic
- Physical state: Solid - Species:
- guinea pig
- Strain:
- Hartley
- Sex:
- male/female
- Details on test animals and environmental conditions:
- No data available
- Route:
- epicutaneous, occlusive
- Vehicle:
- other: Mineral oil
- Concentration / amount:
- 75%
- Day(s)/duration:
- 3week
- Route:
- epicutaneous, open
- Vehicle:
- other: Mineral oil
- Concentration / amount:
- 75%
- Day(s)/duration:
- 48 hour
- No. of animals per dose:
- 10 animals
- Details on study design:
- MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: The test substance was applied once per week until a total of 3 induction applications had been made.
- Concentrations: 75%
B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: Challenge performed 13 days after last induction application
- Concentrations: 75%
- Evaluation (hr after challenge): 24 and 48 - Challenge controls:
- No data available.
- Positive control substance(s):
- yes
- Remarks:
- 1-chloro-2, 4- dinitrobenzene (DNCB)
- Statistics:
- No data available.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 75%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- No skin sensitization reaction observed.
- Remarks on result:
- no indication of skin sensitisation
- Interpretation of results:
- other: Negative
- Conclusions:
- The skin sensitization potential of 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride(59703-00-3) was estimated by using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride (59703-00-3) was predicted to be not sensitizing to the skin of female and male Hartley guinea pig.
- Executive summary:
The skin sensitization potential of 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride(59703-00-3) was estimated by using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride (59703-00-3) was predicted to be not sensitizing to the skin of female and male Hartley guinea pig.
Reference
The
prediction was based on dataset comprised from the following
descriptors: "S M W N"
Estimation method: Takes highest mode value from the 6 nearest neighbours
Domain logical expression:Result: In Domain
((((((((("a"
or "b" or "c" )
and ("d"
and (
not "e")
)
)
and "f" )
and ("g"
and (
not "h")
)
)
and "i" )
and ("j"
and (
not "k")
)
)
and ("l"
and (
not "m")
)
)
and ("n"
and (
not "o")
)
)
and ("p"
and "q" )
)
Domain
logical expression index: "a"
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 >> Alkyl carbamyl halides OR SN1 OR SN1 >> Iminium Ion Formation
OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines by DNA
binding by OECD ONLY
Domain
logical expression index: "b"
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 >> (Thio)Acyl and (thio)carbamoyl halides and
cyanides OR 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
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 Acylation >> Direct Acylation
Involving a Leaving group >> Acyl halides (including benzyl and
carbamoyl deriv.) OR Acylation >> Direct Acylation Involving a Leaving
group >> Dialkyl carbamoylhalides by Protein binding by OECD ONLY
Domain
logical expression index: "d"
Referential
boundary: The
target chemical should be classified as No alert found by DNA binding by
OASIS v.1.3
Domain
logical expression index: "e"
Referential
boundary: The
target chemical should be classified as AN2 OR AN2 >> Michael-type
addition on alpha, beta-unsaturated carbonyl compounds OR AN2 >>
Michael-type addition on alpha, beta-unsaturated carbonyl compounds >>
Four- and Five-Membered Lactones OR AN2 >> Shiff base formation after
aldehyde release OR AN2 >> Shiff base formation after aldehyde release
>> Specific Acetate Esters OR Non-covalent interaction OR Non-covalent
interaction >> DNA intercalation OR Non-covalent interaction >> DNA
intercalation >> Coumarins OR Non-covalent interaction >> DNA
intercalation >> DNA Intercalators with Carboxamide Side Chain OR
Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR
Radical >> Radical mechanism via ROS formation (indirect) >> Coumarins
OR SN1 OR SN1 >> Nucleophilic attack after carbenium ion formation OR
SN1 >> Nucleophilic attack after carbenium ion formation >> Specific
Acetate Esters OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >>
Specific Acetate Esters OR SN2 >> Alkylation, ring opening SN2 reaction
OR SN2 >> Alkylation, ring opening SN2 reaction >> Four- and
Five-Membered Lactones OR SN2 >> Direct acting epoxides formed after
metabolic activation OR SN2 >> Direct acting epoxides formed after
metabolic activation >> Coumarins OR SN2 >> Nucleophilic substitution at
sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom
>> Specific Acetate Esters by DNA binding by OASIS v.1.3
Domain
logical expression index: "f"
Referential
boundary: The
target chemical should be classified as Acylation AND Acylation >>
Direct Addition of an Acyl Halide AND Acylation >> Direct Addition of an
Acyl Halide >> Alkyl carbamyl halides AND SN1 AND SN1 >> Iminium Ion
Formation AND SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines
by DNA binding by OECD ONLY
Domain
logical expression index: "g"
Referential
boundary: The
target chemical should be classified as Not possible to classify
according to these rules by DPRA Cysteine peptide depletion
Domain
logical expression index: "h"
Referential
boundary: The
target chemical should be classified as Low reactive OR Low reactive >>
N-substituted aromatic amides OR Moderate reactive OR Moderate reactive
>> Five-membered heterocyclic urea by DPRA Cysteine peptide depletion
Domain
logical expression index: "i"
Referential
boundary: The
target chemical should be classified as Bioavailable by Lipinski Rule
Oasis ONLY
Domain
logical expression index: "j"
Referential
boundary: The
target chemical should be classified as Halogens AND Non-Metals by
Groups of elements
Domain
logical expression index: "k"
Referential
boundary: The
target chemical should be classified as Alkali Earth by Groups of
elements
Domain
logical expression index: "l"
Referential
boundary: The
target chemical should be classified as Not categorized by Repeated dose
(HESS)
Domain
logical expression index: "m"
Referential
boundary: The
target chemical should be classified as Aliphatic amines (Mucous
membrane irritation) Rank C by Repeated dose (HESS)
Domain
logical expression index: "n"
Referential
boundary: The
target chemical should be classified as Inclusion rules not met by Skin
irritation/corrosion Inclusion rules by BfR
Domain
logical expression index: "o"
Referential
boundary: The
target chemical should be classified as Alkylalkanol-amines OR
Quaternary organic ammonium compounds by Skin irritation/corrosion
Inclusion rules by BfR
Domain
logical expression index: "p"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= -3.02
Domain
logical expression index: "q"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 2.33
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not sensitising)
- Additional information:
Skin sensitization
In different studies, 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride(59703-00-3) has been investigated for potential for dermal sensitization to a greater or lesser extent. The prediction is based on in vivo experiments in guinea pig for target chemical 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride(59703-00-3) and in vivo experiments in human for its structurally similar read across substancesTriethanolamine (102 -17 -6). The predicted data using the OECD QSAR toolbox have also been compared with the experimental data of read across.
The skin sensitization potential of 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride(59703-00-3) was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride (59703-00-3) was predicted to be not sensitizing to the skin of female and male Hartley guinea pig.
Further supported by experimental data conducted by SIDS Initial Assessment Report, SIAM 3 (SIDS Initial Assessment Report for SIAM 3, 1995) on structurally similar read across substance Triethanolamine (102 -17 -6)in humans. The read across substances share high similarity in structure and log kow .Therefore, it is acceptable to derive information on skin sensitization from the analogue substance. The skin sensitization study of Triethanolamine (102 -17 -6) was performed by repeated insult patch test in 64 human volunteers. By using 0.1% Triethanolamine. In induction phase, repeated patch applications was done using 0.1% test substance for 24hr per application at upper arm of the volunteers for 3 times per week for 3 weeks . After 14 days rest period, challenge application of 0.1% test substance was applied on opposite arm of the subject. Evaluation was performed after 48hr and 96hr.No evidence of sensitivity was noted. Hence it is considered that Triethanolamine(102 -17 -6) was not skin sensitizing in human .
Thus based on the above predictions on4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride(59703-00-3) as well as its read across substances and applying weight of evidence, it can be concluded that4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride(59703-00-3) is not a skin sensitizer. Thus comparing the above annotations with the criteria of CLP regulation, 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride(59703-00-3)can be considered as not classified for skin sensitization effects.
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Thus comparing the above annotations with the criteria of CLP regulation, 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride(59703-00-3)can be considered as not classified for skin sensitization effects.
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