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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
LD50 was estimated to be 3727 mg/kg bw when rats were orally exposed with 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride.
Key value for chemical safety assessment
Acute toxicity: via oral route
Link to relevant study records
- Endpoint:
- acute 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 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
- Test type:
- other: No data
- Limit test:
- no
- Specific details on test material used for the study:
- - Name of the test material: 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride
- IUPAC name: 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride
- Molecular Formula: C7H9ClN2O3
- Molecular Weight: 204.612 g/mol
- Substance type: Organic
- Smiles: N1(C(C(=O)N(CC1)CC)=O)C(=O)Cl - Species:
- rat
- Strain:
- not specified
- Sex:
- not specified
- Details on test animals or test system and environmental conditions:
- No data
- Route of administration:
- oral: unspecified
- Vehicle:
- not specified
- Details on oral exposure:
- No data
- Doses:
- 3727 mg/kg bw
- No. of animals per sex per dose:
- No data
- Control animals:
- not specified
- Details on study design:
- No data
- Statistics:
- No data
- Preliminary study:
- No data
- Sex:
- not specified
- Dose descriptor:
- LD50
- Effect level:
- 3 727 mg/kg bw
- Based on:
- test mat.
- Remarks on result:
- other: 50 % mortality observed
- Mortality:
- No data
- Clinical signs:
- other: No data
- Gross pathology:
- No data
- Other findings:
- No data
- Interpretation of results:
- Category 5 based on GHS criteria
- Conclusions:
- LD50 was estimated to be 3727 mg/kg bw when rats were orally exposed with 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloridehas.
- Executive summary:
In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloridehas. The LD50 was estimated to be 3727 mg/kg bw when rats were orally exposed with 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloridehas.
Reference
The
prediction was based on dataset comprised from the following
descriptors: LD50
Estimation method: Takes average 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 (
not "j")
)
)
and ("k"
and (
not "l")
)
)
and "m" )
and ("n"
and (
not "o")
)
)
and ("p"
and (
not "q")
)
)
and "r" )
and ("s"
and (
not "t")
)
)
and ("u"
and (
not "v")
)
)
and ("w"
and (
not "x")
)
)
and ("y"
and "z" )
)
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 OR AN2
>> Schiff base formation >> Dicarbonyl compounds 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 >>
Coumarins 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) >> Coumarins 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, nucleophilic substitution
at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at
sp3-carbon atom >> Sulfonates and Sulfates 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 >> Direct acting epoxides
formed after metabolic activation >> Quinoline Derivatives 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 at an activated carbon atom OR
SN2 >> SN2 at an activated carbon atom >> Quinoline 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 Not known precedent reproductive
and developmental toxic potential by DART scheme v.1.0
Domain
logical expression index: "j"
Referential
boundary: The
target chemical should be classified as ARA inhibitors, Candesartan-like
chemicals (5c-3) OR ARA inhibitors, Candesartan-like chemicals (5c-3) >>
Candesartan-like ARA inhibitors OR Barbital and ETU, PLTU-like
derivatives (17a) OR Imidazole derivatives (13a) OR Known precedent
reproductive and developmental toxic potential OR Purine and
pyrimidine-like derivatives (7b) by DART scheme v.1.0
Domain
logical expression index: "k"
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: "l"
Referential
boundary: The
target chemical should be classified as Alkyl carbamate and
thiocarbamate OR alpha,beta-unsaturated carbonyls OR Hydrazine OR
N-methylol derivatives OR No alert found by in vivo mutagenicity
(Micronucleus) alerts by ISS
Domain
logical expression index: "m"
Referential
boundary: The
target chemical should be classified as Bioavailable by Lipinski Rule
Oasis ONLY
Domain
logical expression index: "n"
Referential
boundary: The
target chemical should be classified as Halogens AND Non-Metals by
Groups of elements
Domain
logical expression index: "o"
Referential
boundary: The
target chemical should be classified as Alkali Earth OR Metalloids by
Groups of elements
Domain
logical expression index: "p"
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: "q"
Referential
boundary: The
target chemical should be classified as Group 16 - Sulfur S by Chemical
elements
Domain
logical expression index: "r"
Similarity
boundary:Target:
CCN1CCN(C(=O)Cl)C(=O)C1=O
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization
Domain
logical expression index: "s"
Referential
boundary: The
target chemical should be classified as Not categorized by Repeated dose
(HESS)
Domain
logical expression index: "t"
Referential
boundary: The
target chemical should be classified as Aliphatic amines (Mucous
membrane irritation) Rank C by Repeated dose (HESS)
Domain
logical expression index: "u"
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: "v"
Referential
boundary: The
target chemical should be classified as Low reactive OR Low reactive >>
N-substituted aromatic amides by DPRA Cysteine peptide depletion
Domain
logical expression index: "w"
Referential
boundary: The
target chemical should be classified as No Data by Ultimate biodeg
Domain
logical expression index: "x"
Referential
boundary: The
target chemical should be classified as > 100 days OR 1 to 10 days OR 10
to 100 days by Ultimate biodeg
Domain
logical expression index: "y"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= -2.39
Domain
logical expression index: "z"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= -0.348
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 3 727 mg/kg bw
- Quality of whole database:
- Data is Kilmisch 2 and from OECD QSAR toolbox
Acute toxicity: via inhalation route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Acute toxicity: via dermal route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Acute oral toxicity:
In different studies, 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride as been investigated for acute oral 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-ethyl-2,3-dioxopiperazine-1-carbonyl chloride along with the study available on structurally similar read across 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 acute oral toxicity was estimated for 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride. The LD50 was estimated to be 3727 mg/kg bw when rats were orally exposed with 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride.
In another prediction done by using Danish QSAR (2017), the acute oral toxicity was estimated for 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride. The LD50 was estimated to be 2400 mg/kg bw when rats were orally exposed with 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride.
Also it is further supported experimental data conducted by Dupont chem (Scientific associates, OTS0571246, report number: 8EHQ-1092-11308, October 15. 1992) on 50-60% structurally similar read across substance Diethylcarbamoyl chloride (CAS: 88-10-8), Sprague Dawlay male and female rats were treated with Diethylcarbamoyl chloride undiluted in the concentration of 2000, 2350, 2600 and 2900 mg/kg bw orally by gavage. All the five female rats were died at 2900 mg/kg bw. Half of deaths occurred in 30 minutes to two hours while the other occurred in 24 to 72 hours. 1 male and 1 female rat died at 2600 mg/kg bw, 1 male rat died at 2350 mg/kg bw and No mortality were observed in treated male and female rats at 2000 mg/kg bw. Muscular in coordination, lethargy, convulsions and coma were observed in died rats. Moderately severe diarrhea was observed in all surviving rats. Decreased in 8 to 15 % body weight was observed in treated rats. In addition, Alteration In Gastric Secretion, severally irritant intestinal mucosa, abnormally dark liver and greenish colure spleen was observed in treated rats. Hemorrhogic area in Liver and congestion of tubule in kidney were observed in treated rats. Therefore, LD50 was estimated to 2700 mg/kg bw when Sprague Dawlay male and female rats were treated with Diethylcarbamoyl chloride orally by gavage.
Thus, based on the above studies and predictions on 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride and its read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus comparing this value with the criteria of CLP regulation, 4-methylphenyl acetate can be ‘Not classified’ for acute oral toxicity.
Justification for classification or non-classification
Thus, based on the above studies and predictions on 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride and its read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus comparing this value with the criteria of CLP regulation, 4-methylphenyl acetate can be ‘Not classified’ for acute oral toxicity.
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