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EC number: 206-137-4 | CAS number: 303-26-4
- 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
Short-term toxicity to aquatic invertebrates
Administrative data
Link to relevant study record(s)
- Endpoint:
- short-term toxicity to aquatic invertebrates
- 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: Predicted data
- Principles of method if other than guideline:
- Prediction is done using QSAR Toolbox version 3.3 with log kow as the primary discriptors.
- GLP compliance:
- not specified
- Specific details on test material used for the study:
- - Name of the test material: 1-[(4-chlorophenyl)(phenyl)methyl]piperazine
- Common Name: Norchlorcyclizine
- IUPAC name: 1-[(4-chlorophenyl)(phenyl)methyl]piperazine
- Molecular weight: 286.804 g/mol
- Molecular formula: C17H19ClN2
- Substance type: Organic
- SMILES Notation: c1([C@@H](c2ccccc2)N2CCNCC2)ccc(Cl)cc1
- InChI: 1S/C17H19ClN2/c18-16-8-6-15(7-9-16)17(14-4-2-1-3-5-14)20-12-10-19-11-13-20/h1-9,17,19H,10-13H2
- Physical State: Solid (white to pale yellow) - Analytical monitoring:
- not specified
- Vehicle:
- not specified
- Test organisms (species):
- Daphnia magna
- Test type:
- static
- Water media type:
- freshwater
- Total exposure duration:
- 48 h
- Key result
- Duration:
- 48 h
- Dose descriptor:
- EC50
- Effect conc.:
- 116.794 mg/L
- Nominal / measured:
- meas. (not specified)
- Conc. based on:
- test mat.
- Basis for effect:
- other: Intoxication
- Remarks on result:
- other: no toxic
- Conclusions:
- Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the closest read across substances, the toxicity to aquatic invertebrate was predicted 1-[(4-chlorophenyl)(phenyl)methyl]piperazine (CAS: 303-26-4). EC50 intoxication value was estimated to be 116.794 mg/l for Daphnia magna for 48 hrs duration. It was concluded that 1-[(4-chlorophenyl)(phenyl)methyl]piperazine (CAS: 303-26-4) was likely to be not toxic to aquatic invertebrate.
- 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 closest read across substances, the toxicity to aquatic invertebrate was predicted 1-[(4-chlorophenyl)(phenyl)methyl]piperazine (CAS: 303-26-4). EC50 intoxication value was estimated to be 116.794 mg/l for Daphnia magna for 48 hrs duration. It was concluded that 1-[(4-chlorophenyl)(phenyl)methyl]piperazine (CAS: 303-26-4) was likely to be not toxic to aquatic invertebrate.
Reference
The
prediction was based on dataset comprised from the following
descriptors: EC50
Estimation method: Takes average value from the 5 nearest neighbours
Domain logical expression:Result: In Domain
((((((((((((("a"
or "b" or "c" or "d" or "e") and("f"
and(not
"g")) ) and("h"
and(not
"i")) ) and("j"
and(not
"k")) ) and
"l") and
"m") and
"n") and("o"
and(not
"p")) ) and("q"
and(not
"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 Secondary amines by OECD HPV
Chemical Categories
Domain
logical expression index: "b"
Referential
boundary:The
target chemical should be classified as Aliphatic Amines by US-EPA New
Chemical Categories
Domain
logical expression index: "c"
Referential
boundary:The
target chemical should be classified as Michael addition AND Michael
addition >> P450 Mediated Activation to Quinones and Quinone-type
Chemicals AND Michael addition >> P450 Mediated Activation to Quinones
and Quinone-type Chemicals >> Arenes AND SN1 AND SN1 >> Iminium Ion
Formation AND SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines
by DNA binding by OECD
Domain
logical expression index: "d"
Referential
boundary:The
target chemical should be classified as Narcotic Amine by Acute aquatic
toxicity MOA by OASIS
Domain
logical expression index: "e"
Referential
boundary:The
target chemical should be classified as Aliphatic Amines by Aquatic
toxicity classification by ECOSAR
Domain
logical expression index: "f"
Referential
boundary:The
target chemical should be classified as No alert found by DNA binding by
OASIS v.1.3
Domain
logical expression index: "g"
Referential
boundary:The
target chemical should be classified as AN2 OR AN2 >> Carbamoylation
after isocyanate formation OR AN2 >> Carbamoylation after isocyanate
formation >> N-Hydroxylamines 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 >> Schiff base formation by aldehyde
formed after metabolic activation >> N-methylol 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 Radical OR Radical >> Radical mechanism via
ROS formation (indirect) OR Radical >> Radical mechanism via ROS
formation (indirect) >> Conjugated Nitro Compounds OR Radical >> Radical
mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane
Derivatives OR Radical >> Radical mechanism via ROS formation (indirect)
>> N-Hydroxylamines OR Radical >> Radical mechanism via ROS formation
(indirect) >> Nitroarenes with Other Active Groups OR SN1 OR SN1 >>
Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic
attack after carbenium ion formation >> N-Nitroso Compounds 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 >> N-Hydroxylamines OR
SN1 >> Nucleophilic attack after nitrenium and/or carbenium ion
formation OR SN1 >> Nucleophilic attack after nitrenium and/or carbenium
ion formation >> N-Nitroso Compounds OR SN1 >> Nucleophilic attack after
reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack
after reduction and nitrenium ion formation >> Conjugated Nitro
Compounds OR SN1 >> Nucleophilic attack after reduction and nitrenium
ion formation >> Nitroarenes with Other Active Groups 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 >> Direct acting epoxides formed after
metabolic activation OR SN2 >> Direct acting epoxides formed after
metabolic activation >> Quinoline Derivatives 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: "h"
Referential
boundary:The
target chemical should be classified as Michael addition AND Michael
addition >> P450 Mediated Activation to Quinones and Quinone-type
Chemicals AND Michael addition >> P450 Mediated Activation to Quinones
and Quinone-type Chemicals >> Arenes AND SN1 AND SN1 >> Iminium Ion
Formation AND SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines
by DNA binding by OECD
Domain
logical expression index: "i"
Referential
boundary:The
target chemical should be classified as Acylation OR Acylation >> P450
Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >>
P450 Mediated Activation to Isocyanates or Isothiocyanates >>
Benzylamines-Acylation OR Michael addition >> P450 Mediated Activation
to Quinones and Quinone-type Chemicals >> Methylenedioxyphenyl 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 >> Ethanolamines
(including morpholine) OR Schiff base formers >> Direct Acting Schiff
Base Formers OR Schiff base formers >> Direct Acting Schiff Base Formers
>> Mono aldehydes OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium
Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion
formation >> Tertiary aromatic amine OR SN2 OR SN2 >> Epoxidation of
Aliphatic Alkenes OR SN2 >> Epoxidation of Aliphatic Alkenes >>
Halogenated polarised alkenes by DNA binding by OECD
Domain
logical expression index: "j"
Referential
boundary:The
target chemical should be classified as No alert found by Protein
binding by OASIS v1.3
Domain
logical expression index: "k"
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 >> Carbamates OR Acylation >> Ester
aminolysis OR Acylation >> Ester aminolysis >> Amides OR Acylation >>
Ester aminolysis >> Dithiocarbamates OR Michael Addition OR Michael
Addition >> Quinone type chemicals OR Michael Addition >> Quinone type
chemicals >> Pyranones, Pyridones (and related nitrogen chemicals) 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
Domain
logical expression index: "l"
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: "m"
Referential
boundary:The
target chemical should be classified as Narcotic Amine by Acute aquatic
toxicity MOA by OASIS ONLY
Domain
logical expression index: "n"
Referential
boundary:The
target chemical should be classified as Bioavailable by Lipinski Rule
Oasis ONLY
Domain
logical expression index: "o"
Referential
boundary:The
target chemical should be classified as Aryl AND Aryl halide AND
Piperazine AND Saturated heterocyclic amine AND Saturated heterocyclic
fragment by Organic Functional groups
Domain
logical expression index: "p"
Referential
boundary:The
target chemical should be classified as Aliphatic Amine, primary by
Organic Functional groups
Domain
logical expression index: "q"
Referential
boundary:The
target chemical should be classified as Aryl AND Aryl halide AND
Piperazine AND Saturated heterocyclic amine AND Saturated heterocyclic
fragment by Organic Functional groups
Domain
logical expression index: "r"
Referential
boundary:The
target chemical should be classified as Cycloalkane by Organic
Functional groups
Domain
logical expression index: "s"
Referential
boundary:The
target chemical should be classified as Aliphatic amine [-NH2 or
-NH-] AND Aromatic chloride [-CL] AND Aromatic-CH AND Aromatic-H AND
-CH2- [cyclic] AND Tertiary amine by Biodegradation fragments (BioWIN
MITI)
Domain
logical expression index: "t"
Referential
boundary:The
target chemical should be classified as Aliphatic ether [C-O-C] by
Biodegradation fragments (BioWIN MITI)
Domain
logical expression index: "u"
Referential
boundary:The
target chemical should be classified as Aliphatic amine [-NH2 or
-NH-] AND Aromatic chloride [-CL] AND Aromatic-CH AND Aromatic-H AND
-CH2- [cyclic] AND Tertiary amine by Biodegradation fragments (BioWIN
MITI)
Domain
logical expression index: "v"
Referential
boundary:The
target chemical should be classified as -C=CH [alkenyl hydrogen] by
Biodegradation fragments (BioWIN MITI)
Domain
logical expression index: "w"
Referential
boundary:The
target chemical should be classified as Aliphatic Amines by Aquatic
toxicity classification by ECOSAR
Domain
logical expression index: "x"
Referential
boundary:The
target chemical should be classified as Nicotinoids by Aquatic toxicity
classification by ECOSAR
Domain
logical expression index: "y"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= 0.906
Domain
logical expression index: "z"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 4.46
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 closest read across substances, the toxicity to aquatic invertebrate was predicted 1-[(4-chlorophenyl)(phenyl)methyl]piperazine (CAS: 303-26-4). EC50 intoxication value was estimated to be 116.794 mg/l for Daphnia magna for 48 hrs duration. It was concluded that 1-[(4-chlorophenyl)(phenyl)methyl]piperazine (CAS: 303-26-4) was likely to be not toxic to aquatic invertebrate.
Key value for chemical safety assessment
Fresh water invertebrates
Fresh water invertebrates
- Effect concentration:
- 116.794 mg/L
Additional information
Following studies of target chemical and structurally similar read across includes predicted data and experimental data to conclude the toxicity extent of 1-[(4-chlorophenyl)(phenyl)methyl]piperazine (CAS: 303-26-4) towards aquatic invertebrate is summarized as follows:
Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the closest read across substances, the toxicity to aquatic invertebrate was predicted 1-[(4-chlorophenyl)(phenyl)methyl]piperazine (CAS: 303-26-4). EC50 intoxication value was estimated to be 116.794 mg/l for Daphnia magna for 48 hrs duration. It was concluded that 1-[(4-chlorophenyl)(phenyl)methyl]piperazine (CAS: 303-26-4) was likely to be not toxic to aquatic invertebrate.
The above predicted data of target chemical is supported by the experimental study of structurally similar read across disodium 2-dibutylaminoethanol (CAS: 102 -81 -8) from the J-CHeck, suggests that the Short term toxicity test was carried out acoording to the OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test) to study the effects on aquatic environment. mobility was measured during the test. The effective concentration to 50% of Daphnia magna when exposed to 2-dibutylaminoethanol for 48 hr is >110 mg/L. It can be concluded from the value that 2-dibutylaminoethanol (CAS: 102 -81 -8) is not toxic/toxic to the aquatic invertebrate and can be considered as “not classified” as per the classification criteria for aquatic environment.
Another supporting experimental study for the structurally similar read across piperazine (CAS: 110-85-0) from the J-CHeck 2017, also suggests that the Short term toxicity to aquatic invertebrates was performed according to the OECD guideline 202.The test was conducted for 48 hrs and EC 50 value was observed.
After experiment the EC50 value for short term toxicity to aquatic invertebrates for piperazine (CAS: 110-85-0) was determined to be 110 mg/l.
On the basis of results for toxicity to aquatic invertebrates, it can be considered that the substance is not likely to be toxic to aquatic invertebrates and can be considered as not classified as per the CLP regulation.
Thus based on the effect concentrations which is in the range 110 mg/l to 116.794 mg/l give the conclusion that test substance 1-[(4-chlorophenyl)(phenyl)methyl]piperazine (CAS: 303-26-4) was likely to be not toxic to aquatic invertebrate at environmentally relevant concentrations and can be considered to be “not classified” as per the CLP classification criteria.
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