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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
Skin Irritation:
The dermal irritation potential of 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride (CAS No: 59703-00-3) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride (CAS No: 59703-00-3) was estimated to be not irritating to the skin of Vienna White rabbits.
Based on the estimated result, 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride (CAS No: 59703-00-3) can be considered to be not irritating to skin and can be classified under the category "Not Classified" as per CLP regulation.
Eye Irritation:
The ocular irritation potential of 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride (CAS No: 59703-00-3) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor.4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride (CAS No: 59703-00-3) was estimated to be not irritating to the eyes of Vienna White rabbits.
Based on the estimated result, 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride (CAS No: 59703-00-3) can be considered to be not irritating to eye and can be classified under the category "Not Classified"as per CLP regulation.
Key value for chemical safety assessment
Skin irritation / corrosion
Link to relevant study records
- Endpoint:
- skin irritation: 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:
- other: Estimated data
- Principles of method if other than guideline:
- Prediction is done using QSAR Toolbox version 3.3
- GLP compliance:
- 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:
- rabbit
- Strain:
- Vienna White
- Details on test animals or test system and environmental conditions:
- no data available
- Type of coverage:
- occlusive
- Preparation of test site:
- not specified
- Vehicle:
- unchanged (no vehicle)
- Controls:
- not specified
- Amount / concentration applied:
- No data available
- Duration of treatment / exposure:
- 1, 5, 15 min20 h
- Observation period:
- 8 days
- Number of animals:
- 2
- Details on study design:
- no data available
- Other effects / acceptance of results:
- no data available
- Irritation parameter:
- overall irritation score
- Basis:
- mean
- Time point:
- other: 8 days
- Reversibility:
- not specified
- Remarks on result:
- no indication of irritation
- Irritant / corrosive response data:
- No irritation was observed.
- Interpretation of results:
- other: not irritating
- Conclusions:
- 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride (CAS No: 59703-00-3) was estimated to be not irritating to the skin of Vienna White rabbits.
- Executive summary:
The dermal irritation potential of 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride (CAS No: 59703-00-3) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride (CAS No: 59703-00-3) was estimated to be not irritating to the skin of Vienna White rabbits.
Based on the estimated result, 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride (CAS No: 59703-00-3) can be considered to be not irritating to skin and can be classified under the category "Not Classified" as per CLP regulation.
Reference
Estimation
method: Takes mode value from the 5 nearest neighbours
Domain logical expression:Result: In Domain
(((((((((((((((((("a"
or "b" or "c" )
and "d" )
and ("e"
and (
not "f")
)
)
and ("g"
and (
not "h")
)
)
and ("i"
and (
not "j")
)
)
and ("k"
and (
not "l")
)
)
and ("m"
and (
not "n")
)
)
and ("o"
and (
not "p")
)
)
and ("q"
and (
not "r")
)
)
and ("s"
and (
not "t")
)
)
and ("u"
and (
not "v")
)
)
and "w" )
and "x" )
and "y" )
and "z" )
and ("aa"
and (
not "ab")
)
)
and "ac" )
and ("ad"
and "ae" )
)
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 Bioavailable by Lipinski Rule
Oasis ONLY
Domain
logical expression index: "e"
Referential
boundary: The
target chemical should be classified as Halogens AND Non-Metals by
Groups of elements
Domain
logical expression index: "f"
Referential
boundary: The
target chemical should be classified as Alkali Earth OR Alkaline Earth
OR Metalloids OR Transition Metals by Groups of elements
Domain
logical expression index: "g"
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: "h"
Referential
boundary: The
target chemical should be classified as Group 15 - Phosphorus P OR Group
16 - Sulfur S OR Group 17 - Halogens Br OR Group 17 - Halogens F OR
Group 17 - Halogens I by Chemical elements
Domain
logical expression index: "i"
Referential
boundary: The
target chemical should be classified as Not categorized by Repeated dose
(HESS)
Domain
logical expression index: "j"
Referential
boundary: The
target chemical should be classified as 3-Methylcholantrene
(Hepatotoxicity) Alert OR Aliphatic amines (Mucous membrane irritation)
Rank C OR Aliphatic nitriles (Hepatotoxicity) Rank B OR Allyl esters
(Hepatotoxicity) Rank A OR Chlorphentermine (Hepatotoxicity) Alert OR
Dantrolene (Hepatotoxicity) Alert OR Fialuridine (Hepatotoxicity) Alert
OR Oxyphenistain (Hepatotoxicity) Alert OR Perhexiline (Hepatotoxicity)
Alert OR Valproic acid (Hepatotoxicity) Alert by Repeated dose (HESS)
Domain
logical expression index: "k"
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: "l"
Referential
boundary: The
target chemical should be classified as Acid anhydrides OR Acyl halides
OR Alkylalkanol-amines OR Aromatic amines OR Esters including acrylic
and methacrylic esters OR Ethylenglycolethers OR Ketones OR Lactones OR
Phenols OR Substituted benzoic acid halogenides by Skin
irritation/corrosion Inclusion rules by BfR
Domain
logical expression index: "m"
Referential
boundary: The
target chemical should be classified as No alert found by Respiratory
sensitisation
Domain
logical expression index: "n"
Referential
boundary: The
target chemical should be classified as Acylation OR Acylation >> Direct
acylation at a carbonyl with a leaving group OR Acylation >> Direct
acylation at a carbonyl with a leaving group >> Acyl chlorides OR
Acylation >> Direct acylation at a carbonyl with a leaving group >>
Phenyl acetates by Respiratory sensitisation
Domain
logical expression index: "o"
Referential
boundary: The
target chemical should be classified as No alert found by Protein
binding alerts for Chromosomal aberration by OASIS v1.1
Domain
logical expression index: "p"
Referential
boundary: The
target chemical should be classified as AN2 OR AN2 >> Michael addition
to activated double bonds in heterocyclic ring systems OR AN2 >> Michael
addition to activated double bonds in heterocyclic ring systems >>
Pyrazolone and Pyrazolidine Derivatives OR AN2 >> Michael type addition
to activated double bond of pyrimidine bases OR AN2 >> Michael type
addition to activated double bond of pyrimidine bases >> Pyrimidines and
Purines OR AN2 >> Shiff base formation with carbonyl compounds OR AN2 >>
Shiff base formation with carbonyl compounds >> Pyrazolone and
Pyrazolidine Derivatives OR AN2 >> Shiff base formation with carbonyl
group of pyrimidine or purine bases OR AN2 >> Shiff base formation with
carbonyl group of pyrimidine or purine bases >> Pyrimidines and Purines
OR SN2 OR SN2 >> Alkylation, nucleophilic subsitution at sp3-Carbon atom
OR SN2 >> Alkylation, nucleophilic subsitution at sp3-Carbon atom >>
Alpha-Activated Haloalkanes by Protein binding alerts for Chromosomal
aberration by OASIS v1.1
Domain
logical expression index: "q"
Referential
boundary: The
target chemical should be classified as Acyl halides AND
H-acceptor-path3-H-acceptor by in vivo mutagenicity (Micronucleus)
alerts by ISS
Domain
logical expression index: "r"
Referential
boundary: The
target chemical should be classified as Aliphatic halogen OR Aliphatic
N-nitro group OR Alkyl carbamate and thiocarbamate OR
alpha,beta-unsaturated aliphatic alkoxy group OR alpha,beta-unsaturated
carbonyls OR Aromatic N-acyl amine OR Hydrazine OR Nitro-aromatic OR
N-methylol derivatives OR No alert found OR Polycyclic Aromatic
Hydrocarbons by in vivo mutagenicity (Micronucleus) alerts by ISS
Domain
logical expression index: "s"
Referential
boundary: The
target chemical should be classified as Inclusion rules not met by Eye
irritation/corrosion Inclusion rules by BfR
Domain
logical expression index: "t"
Referential
boundary: The
target chemical should be classified as Aliphatic esters of chloro
formic acid OR Pyrrolidones by Eye irritation/corrosion Inclusion rules
by BfR
Domain
logical expression index: "u"
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: "v"
Referential
boundary: The
target chemical should be classified as 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) >> Alkyl formamide analogs OR Alkyl amide,
urea, thiourea, nitroso urea, carbonate, guanidine and carbamate
derivatives (21b1) >> Alkylamide or thioamide analogs OR Allantoin and
dimethadione-like derivatives (17b) OR Barbital and ETU, PLTU-like
derivatives (17a) OR Di-substituted hydrocarbons (24a) OR Known
precedent reproductive and developmental toxic potential OR Metal
chelators 24 (d, e, f) OR Miscellaneous cyclic chemicals (18) OR Purine
and pyrimidine-like derivatives (7b) OR Toluene and small alkyl toluene
derivatives (8a) by DART scheme v.1.0
Domain
logical expression index: "w"
Referential
boundary: The
target chemical should be classified as Very fast by Bioaccumulation -
metabolism half-lives ONLY
Domain
logical expression index: "x"
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: "y"
Referential
boundary: The
target chemical should be classified as High (Class III) by Toxic hazard
classification by Cramer (with extensions) ONLY
Domain
logical expression index: "z"
Referential
boundary: The
target chemical should be classified as Not calculated by Hydrolysis
half-life (pH 6.5-7.4) ONLY
Domain
logical expression index: "aa"
Referential
boundary: The
target chemical should be classified as Non binder, without OH or NH2
group by Estrogen Receptor Binding
Domain
logical expression index: "ab"
Referential
boundary: The
target chemical should be classified as Non binder, non cyclic structure
by Estrogen Receptor Binding
Domain
logical expression index: "ac"
Referential
boundary: The
target chemical should be classified as weeks - months by Biodeg
ultimate (Biowin 3) ONLY
Domain
logical expression index: "ad"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= -1.91
Domain
logical expression index: "ae"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= -1.1
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Eye irritation
Link to relevant study records
- Endpoint:
- eye irritation: 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:
- other: estimated data
- Principles of method if other than guideline:
- Prediction is done using QSAR Toolbox version 3.3
- GLP compliance:
- 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:
- rabbit
- Strain:
- Vienna White
- Details on test animals or tissues and environmental conditions:
- no data available
- Vehicle:
- unchanged (no vehicle)
- Controls:
- not specified
- Amount / concentration applied:
- 0.05 mL
- Duration of treatment / exposure:
- 24 hours
- Observation period (in vivo):
- 8 days
- Duration of post- treatment incubation (in vitro):
- no data available
- Number of animals or in vitro replicates:
- 2 rabbits
- Details on study design:
- no data available
- Other effects / acceptance of results:
- no data available
- Irritation parameter:
- overall irritation score
- Basis:
- mean
- Time point:
- other: 8 days
- Reversibility:
- not specified
- Remarks on result:
- no indication of irritation
- Irritant / corrosive response data:
- no irritation was observed.
- Interpretation of results:
- other: not irritating
- Conclusions:
- 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride (CAS No: 59703-00-3) was estimated to be not irritating to the eyes of Vienna White rabbits.
- Executive summary:
The ocular irritation potential of 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride (CAS No: 59703-00-3) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor.
4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride (CAS No: 59703-00-3) was estimated to be not irritating to the eyes of Vienna White rabbits.
Based on the estimated result, 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride (CAS No: 59703-00-3) can be considered to be not irritating to eye and can be classified under the category "Not Classified" as per CLP regulation.
Reference
Estimation
method: Takes mode value from the 5 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 ("m"
and (
not "n")
)
)
and ("o"
and (
not "p")
)
)
and ("q"
and "r" )
)
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 >> Schiff base formation by
aldehyde formed after metabolic activation OR AN2 >> Schiff base
formation by aldehyde formed after metabolic activation >> Geminal
Polyhaloalkane Derivatives OR AN2 >> Shiff base formation after aldehyde
release OR AN2 >> Shiff base formation after aldehyde release >>
Specific Acetate Esters OR AN2 >> Shiff base formation for aldehydes OR
AN2 >> Shiff base formation for aldehydes >> Geminal Polyhaloalkane
Derivatives OR Non-covalent interaction OR Non-covalent interaction >>
DNA intercalation OR Non-covalent interaction >> DNA intercalation >>
DNA Intercalators with Carboxamide Side Chain OR Non-specific OR
Non-specific >> Incorporation into DNA/RNA, due to structural analogy
with nucleoside bases OR Non-specific >> Incorporation into DNA/RNA,
due to structural analogy with nucleoside bases >> Specific Imine
and Thione Derivatives OR Radical OR Radical >> Generation of reactive
oxygen species OR Radical >> Generation of reactive oxygen species >>
N,N-Dialkyldithiocarbamate Derivatives OR Radical >> Radical mechanism
via ROS formation (indirect) OR Radical >> Radical mechanism via ROS
formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >>
Radical mechanism via ROS formation (indirect) >> Nitro Azoarenes OR
Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes
with Other Active Groups OR Radical >> Radical mechanism via ROS
formation (indirect) >> p-Substituted Mononitrobenzenes OR Radical >>
Radical mechanism via ROS formation (indirect) >> Single-Ring
Substituted Primary Aromatic Amines OR Radical >> Radical mechanism via
ROS formation (indirect) >> Specific Imine and Thione Derivatives OR SN1
OR SN1 >> Alkylation after metabolically formed carbenium ion species OR
SN1 >> Alkylation after metabolically formed carbenium ion species >>
Polycyclic Aromatic Hydrocarbon Derivatives OR SN1 >> Nucleophilic
attack after carbenium ion formation OR SN1 >> Nucleophilic attack after
carbenium ion formation >> Specific Acetate Esters OR SN1 >>
Nucleophilic attack after diazonium or carbenium ion formation OR SN1 >>
Nucleophilic attack after diazonium or carbenium ion formation >>
Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after
metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after
metabolic nitrenium ion formation >> Single-Ring Substituted Primary
Aromatic Amines OR SN1 >> Nucleophilic attack after reduction and
nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction
and nitrenium ion formation >> Nitro Azoarenes OR SN1 >> Nucleophilic
attack after reduction and nitrenium ion formation >> Nitroarenes with
Other Active Groups OR SN1 >> Nucleophilic attack after reduction and
nitrenium ion formation >> p-Substituted Mononitrobenzenes OR SN1 >>
Nucleophilic substitution on diazonium ions OR SN1 >> Nucleophilic
substitution on diazonium ions >> Specific Imine and Thione Derivatives
OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate
Esters OR SN2 >> Acylation involving a leaving group OR SN2 >>
Acylation involving a leaving group >> Geminal Polyhaloalkane
Derivatives OR SN2 >> Acylation involving a leaving group after
metabolic activation OR SN2 >> Acylation involving a leaving group after
metabolic activation >> Geminal Polyhaloalkane Derivatives OR SN2 >>
Alkylation, direct acting epoxides and related after P450-mediated
metabolic activation OR SN2 >> Alkylation, direct acting epoxides and
related after P450-mediated metabolic activation >> Polycyclic Aromatic
Hydrocarbon Derivatives OR SN2 >> Alkylation, ring opening SN2 reaction
OR SN2 >> Alkylation, ring opening SN2 reaction >> Four- and
Five-Membered Lactones OR SN2 >> Direct acylation involving a leaving
group OR SN2 >> Direct acylation involving a leaving group >> Acyl
Halides OR SN2 >> DNA alkylation OR SN2 >> DNA alkylation >> Vicinal
Dihaloalkanes OR SN2 >> Internal SN2 reaction with aziridinium and/or
cyclic sulfonium ion formation (enzymatic) OR SN2 >> Internal SN2
reaction with aziridinium and/or cyclic sulfonium ion formation
(enzymatic) >> Vicinal Dihaloalkanes OR SN2 >> Nucleophilic substitution
at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon
atom >> Specific Acetate Esters OR SN2 >> Nucleophilic substitution at
sp3 carbon atom after thiol (glutathione) conjugation OR SN2 >>
Nucleophilic substitution at sp3 carbon atom after thiol (glutathione)
conjugation >> Geminal Polyhaloalkane Derivatives OR SN2 >> SN2 attack
on activated carbon Csp3 or Csp2 OR SN2 >> SN2 attack on activated
carbon Csp3 or Csp2 >> Nitroarenes with Other Active Groups 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 Non binder, without OH or NH2
group by Estrogen Receptor Binding
Domain
logical expression index: "h"
Referential
boundary: The
target chemical should be classified as Non binder, impaired OH or NH2
group OR Non binder, MW>500 OR Non binder, non cyclic structure by
Estrogen Receptor Binding
Domain
logical expression index: "i"
Referential
boundary: The
target chemical should be classified as Acylation AND Acylation >>
Direct Acylation Involving a Leaving group AND Acylation >> Direct
Acylation Involving a Leaving group >> Acetates AND Acylation >> Direct
Acylation Involving a Leaving group >> Acyl halides (including benzyl
and carbamoyl deriv.) AND Acylation >> Direct Acylation Involving a
Leaving group >> Dialkyl carbamoylhalides by Protein binding by OECD ONLY
Domain
logical expression index: "j"
Referential
boundary: The
target chemical should be classified as Inclusion rules not met by Eye
irritation/corrosion Inclusion rules by BfR
Domain
logical expression index: "k"
Referential
boundary: The
target chemical should be classified as Pyrrolidones by Eye
irritation/corrosion Inclusion rules by BfR
Domain
logical expression index: "l"
Referential
boundary: The
target chemical should be classified as Bioavailable by Lipinski Rule
Oasis ONLY
Domain
logical expression index: "m"
Referential
boundary: The
target chemical should be classified as Stable form by Tautomers unstable
Domain
logical expression index: "n"
Referential
boundary: The
target chemical should be classified as Conjugated ketoamine(scy) -
1,5-H shift by Tautomers unstable
Domain
logical expression index: "o"
Referential
boundary: The
target chemical should be classified as Not categorized by US-EPA New
Chemical Categories
Domain
logical expression index: "p"
Referential
boundary: The
target chemical should be classified as Aliphatic Amines OR Hindered
Amines OR Imides (Acute toxicity) by US-EPA New Chemical Categories
Domain
logical expression index: "q"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= -2.37
Domain
logical expression index: "r"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= -0.388
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Respiratory irritation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Skin Irritation:
In different studies, 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride has been investigated for potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with predicted data for target chemical and its functionally similar read across substances 1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione (CAS: 58-55-9) and 1,3 -bis(hydroxymethyl)-5,5-dimethylimidazolidine-2,4-dione (CAS: 6440-58-0). The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.
In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the skin irritation potential was estimated for4-ethyl-2,3 -dioxopiperazine-1-carbonyl chloride. 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride was not irritating to Vienna White rabbit skin.
This result was supported by the study summarized in IUCLID Dataset,2000 for thefunctionally similar read across substance 1,3-dimethyl-3,7-dihydro-1H-purine-2,6 -dione (CAS: 58-55-9).The study was performed in accordance with OECD Guideline 404 "Acute Dermal Irritation/Corrosion". the rabbits were exposed to 500mg of 50% test chemical for 4 hours exposure period under semi-occlusive condition.
After 4 h, the application patches were removed, and the application sites were washed. Scoring was made at 4, 24, 48, and 72 hours after beginning of the study. Very slight reddening was observed in the 2 females at 4 hours. No other signs of irritation were noted. As the mean irritation index was 0.0, the test chemical Theophylline(CAS No:-58-55-9) was considered to be not irritating to the skin of White Vienna rabbits.
The above studies are also supported by the experimental study summarized in REPORTS of the Scientific Committee on Cosmetology (sixth series)- Commission of the European Communities ,Luxembourg; 1987, forthefunctionally similar read across substance 1,3-bis(hydroxymethyl)-5,5-dimethylimidazolidine-2,4-dione (CAS: 6440-58-0). 0.5 ml of test chemical was applied in to the intact or abraded skin of rabbits and later observed for any skin reactions. No known skin irritating effects were observed at this concentration. Hence the test chemical, 1,3 -Dimethylol-5,5-dimethylhydantoin(CAS No:-6440-58-0) was considered to be not irritating to the rabbits’ skin.
Based on the available data for the target and read across substances and applying the weight of evidence approach, 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride can be considered to be not irritating to skin.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.
Eye Irritation:
In different studies, 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride has been investigated for potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with predicted data for target chemical and its functionally similar read across substances 1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione (CAS: 58-55-9); 1,3-bis(hydroxymethyl)-5,5-dimethylimidazolidine-2,4-dione (CAS: 6440-58-0) and structurally similar substance Diethylcarbamoyl chloride (CAS: 88-10-8). The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.
In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the ocular irritation potential was estimated for 4-ethyl-2,3 -dioxopiperazine-1-carbonyl chloride. 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride was not irritating to Vienna White rabbit eyes.
This result was supported by the study summarized in IUCLID Dataset,2000 for thefunctionally similar read across substance 1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione (CAS: 58-55-9). The study was performed in accordance with OECD Guideline 405 "Acute Eye Irritation/Corrosion". The test substance was placed into the right conjunctival sac of each of 3 male White Vienna rabbits. The eyes were not rinsed. Scoring was made at 1, 24, 48, and 72 hours and at 8 days after instillation. Very slight corneal opacity was observed in 1-2 rabbits up to day 8. Slight to well-defined conjunctival redness and conjunctival swellings were observed in all 3 rabbits up to 72h and 48h, respectively. Mean irritation indices were 0.6 (corneal opacity), 0.0 (iritis), 1.8 (conjunctival redness), and 0.6 (conjunctival swelling).On day 8 one animal showed conjuctiva redness (grad 2) and slight cornea opacity (grad 1) and keratitis. The effects could possibly be due to mechanical irritation by the crystalline test substance. The iris was unaffected in each animal at each time. The findings were reversible in 2 of the 3 animals. The findings were reversible in 2 of the 3 animals. Hence the test chemical, Theophylline (CAS No:-58-55-9) was considered to be not irritating to the eyes of White Vienna rabbits.
The above are also supported by the experimental study summarized in GESTIS SUBSTANCE Database (information system in hazardous substance of the Berufsgenossenscheftn), 2017, for the structurally similar substance Diethylcarbamoyl chloride (CAS: 88-10-8). 0.5 ml of the test sample was installed into rabbits’ eyes caused severe irritation to the conjunctiva after 1 hour with formation of slight edema and delayed development of corneal opacity which was later reversible. As all the observed effects were reversible after 1 hour, the test chemical Diethylcarbamoyl chloride (CAS No:- 88-10-8 ) was considered to be not irritating to the rabbits’ eye.
These results are further supported by the experimental study summarized in REPORTS of the Scientific Committee on Cosmetology (sixth series)- Commission of the European Communities ,Luxembourg; 1987, forthefunctionally similar read across substance 1,3-bis(hydroxymethyl)-5,5-dimethylimidazolidine-2,4-dione (CAS: 6440-58-0). 1% of 1,3-bis(hydroxymethyl)-5,5-dimethylimidazolidine-2,4-dione was instilled in to rabbit eyes and observed for any ocular changes. Since the chemical did not induce any adverse effects at 1% concentration, the test chemical1,3-Dimethylol-5,5-dimethylhydantoin(CAS No:-6440-58-0) was considered to be not irritating to the rabbits’ eye.
Based on the available data for the target and read across substances and applying the weight of evidence approach, 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride can be considered to be not irritating to eyes.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
Available studies for4-ethyl-2,3-dioxopiperazine-1-carbonyl chloridesuggest that it is not irritating to eyes and skin. Hence,4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride can be classified under the category “Not Classified” as per CLP regulation.
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