Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
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
Endpoint summary
Administrative data
Description of key information
Skin Irritation:
The dermal irritation potential of 1-[(4-chlorophenyl)(phenyl)methyl]piperazine was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor.
1-[(4-chlorophenyl)(phenyl)methyl]piperazine was estimated to be corrosive to the skin of New Zealand White rabbits.
Based on the estimated result;1-[(4-chlorophenyl)(phenyl)methyl]piperazine can be considered corrosive to skin and can be classified under the category “Category 1” as per CLP regulation.
Eye Irritation:
The ocular irritation potential of 1-[(4-chlorophenyl)(phenyl)methyl]piperazine was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor.
1-[(4-chlorophenyl)(phenyl)methyl]piperazine was estimated to be corrosive to the eyes of New Zealand White rabbits.
Based on the estimated result;1-[(4-chlorophenyl)(phenyl)methyl]piperazine can be considered corrosive to the eyes and can be classified under the category “Category 1” 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 v3.3 and the QMRF report has been attached
- Qualifier:
- according to guideline
- Guideline:
- other: Estimated data
- Principles of method if other than guideline:
- Prediction was done using OECD QSAR toolbox v.3.3
- 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 - Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- no data available
- Type of coverage:
- semiocclusive
- Preparation of test site:
- clipped
- Vehicle:
- not specified
- Controls:
- not specified
- Amount / concentration applied:
- 0.5ml
- Duration of treatment / exposure:
- 4 hours
- Observation period:
- 20 hours
- Number of animals:
- 1
- 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: 20 hours
- Reversibility:
- not specified
- Remarks on result:
- positive indication of irritation
- Irritant / corrosive response data:
- Corrosive effects observed
- Interpretation of results:
- Category 1 (corrosive) based on GHS criteria
- Conclusions:
- 1-[(4-chlorophenyl)(phenyl)methyl]piperazine was estimated to be corrosive to the skin of New Zealand White rabbits.
- Executive summary:
The dermal irritation potential of 1-[(4-chlorophenyl)(phenyl)methyl]piperazine was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor.
1-[(4-chlorophenyl)(phenyl)methyl]piperazine was estimated to be corrosive to the skin of New Zealand White rabbits.
Based on the estimated result;1-[(4-chlorophenyl)(phenyl)methyl]piperazine can be considered corrosive to skin and can be classified under the category “Category 1” 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" or "d" or "e" )
and ("f"
and (
not "g")
)
)
and ("h"
and (
not "i")
)
)
and ("j"
and (
not "k")
)
)
and ("l"
and (
not "m")
)
)
and ("n"
and (
not "o")
)
)
and "p" )
and ("q"
and (
not "r")
)
)
and "s" )
and ("t"
and (
not "u")
)
)
and ("v"
and (
not "w")
)
)
and "x" )
and "y" )
and ("z"
and "aa" )
)
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 >> 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 >> DNA Intercalators with Carboxamide Side Chain OR
Radical OR Radical >> Generation of reactive oxygen species OR Radical
>> Generation of reactive oxygen species >> Thiols OR Radical >> Radical
mechanism via ROS formation (indirect) OR Radical >> Radical mechanism
via ROS formation (indirect) >> N-Hydroxylamines OR Radical >> Radical
mechanism via ROS formation (indirect) >> Single-Ring Substituted
Primary Aromatic Amines 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 >> Carbenium ion formation OR SN1 >> Carbenium ion
formation >> Alpha-Haloethers OR SN1 >> Nucleophilic attack after
carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium
ion formation >> Specific Acetate Esters 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 metabolic nitrenium ion formation >>
Single-Ring Substituted Primary Aromatic Amines OR SN2 OR SN2 >>
Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >>
Alkylation, direct acting epoxides and related OR SN2 >> Alkylation,
direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >>
Alkylation, direct acting epoxides and related after cyclization OR SN2
>> Alkylation, direct acting epoxides and related after cyclization >>
Nitrogen Mustards 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 >> Nucleophilic substitution at sp3 Carbon atom OR
SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate
Esters OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom
>> Alpha-Haloethers 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 Acylation >> P450 Mediated Activation to
Isocyanates or Isothiocyanates >> Formamides OR Michael addition >> P450
Mediated Activation of Heterocyclic Ring Systems OR Michael addition >>
P450 Mediated Activation of Heterocyclic Ring Systems >>
Thiophenes-Michael addition OR Michael addition >> P450 Mediated
Activation to Quinones and Quinone-type Chemicals >> Alkyl phenols OR
Michael addition >> Polarised Alkenes-Michael addition OR Michael
addition >> Polarised Alkenes-Michael addition >> Alpha, beta-
unsaturated amides 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
>> Chemicals Activated by P450 to Glyoxal >> Ethylenediamines
(including piperazine) OR Schiff base formers >> Chemicals Activated by
P450 to Mono-aldehydes OR Schiff base formers >> Chemicals Activated by
P450 to Mono-aldehydes >> Benzylamines-Schiff base OR SN1 >> Nitrenium
Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1
>> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion
formation >> Primary (unsaturated) heterocyclic amine OR SN1 >>
Nitrenium Ion formation >> Tertiary (unsaturated) heterocyclic amine OR
SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN2 OR SN2
>> P450 Mediated Epoxidation OR SN2 >> P450 Mediated Epoxidation >>
Thiophenes-SN2 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 OECD
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 >> Acetates OR Acylation >> Ring Opening
Acylation OR Acylation >> Ring Opening Acylation >> alpha-Lactams OR SN2
OR SN2 >> SN2 reaction at a sulphur atom OR SN2 >> SN2 reaction at a
sulphur atom >> Disulfides by Protein binding by OECD
Domain
logical expression index: "l"
Referential
boundary: The
target chemical should be classified as No alert found by Protein
binding by OASIS v1.3
Domain
logical expression index: "m"
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 by Protein binding by OASIS v1.3
Domain
logical expression index: "n"
Referential
boundary: The
target chemical should be classified as No alert found by
Carcinogenicity (genotox and nongenotox) alerts by ISS
Domain
logical expression index: "o"
Referential
boundary: The
target chemical should be classified as Aliphatic N-nitro group
(Genotox) OR alpha,beta-unsaturated carbonyls (Genotox) OR Halogenated
benzene (Nongenotox) OR Hydrazine (Genotox) OR Metals, oxidative stress
(Nongenotox) OR Structural alert for genotoxic carcinogenicity OR
Structural alert for nongenotoxic carcinogenicity by Carcinogenicity
(genotox and nongenotox) alerts by ISS
Domain
logical expression index: "p"
Referential
boundary: The
target chemical should be classified as Narcotic Amine by Acute aquatic
toxicity MOA by OASIS ONLY
Domain
logical expression index: "q"
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: "r"
Referential
boundary: The
target chemical should be classified as Alkylalkanol-amines OR Ketones
OR Tertiary aliphatic amine by Skin irritation/corrosion Inclusion rules
by BfR
Domain
logical expression index: "s"
Referential
boundary: The
target chemical should be classified as Bioavailable by Lipinski Rule
Oasis ONLY
Domain
logical expression index: "t"
Referential
boundary: The
target chemical should be classified as Halogens AND Non-Metals by
Groups of elements
Domain
logical expression index: "u"
Referential
boundary: The
target chemical should be classified as Alkali Earth by Groups of
elements
Domain
logical expression index: "v"
Referential
boundary: The
target chemical should be classified as Group 14 - Carbon C AND Group 15
- Nitrogen N AND Group 17 - Halogens Cl AND Group 17 - Halogens
F,Cl,Br,I,At by Chemical elements
Domain
logical expression index: "w"
Referential
boundary: The
target chemical should be classified as Group 16 - Oxygen O by Chemical
elements
Domain
logical expression index: "x"
Similarity
boundary:Target:
Clc1ccc(C(c2ccccc2)N2CCNCC2)cc1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization
Domain
logical expression index: "y"
Similarity
boundary:Target:
Clc1ccc(C(c2ccccc2)N2CCNCC2)cc1
Threshold=40%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization
Domain
logical expression index: "z"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= 0.526
Domain
logical expression index: "aa"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 4.47
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (corrosive)
Eye irritation
Link to relevant study records
- Endpoint:
- eye irritation: in vivo
- Type of information:
- calculation (if not (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 v3.3 and the QMRF report has been attached
- Qualifier:
- according to guideline
- Guideline:
- other: Estimated data
- Principles of method if other than guideline:
- Prediction was done using OECD QSAR toolbox v3.3
- 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 - Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or tissues and environmental conditions:
- no data available
- Vehicle:
- not specified
- Controls:
- not specified
- Amount / concentration applied:
- 0.1ml
- Duration of treatment / exposure:
- 24 hours
- Observation period (in vivo):
- 7 days
- Duration of post- treatment incubation (in vitro):
- no data available
- Number of animals or in vitro replicates:
- 1
- Details on study design:
- no data available
- Other effects / acceptance of results:
- no data available
- Irritation parameter:
- overall irritation score
- Basis:
- mean
- Time point:
- 7 d
- Reversibility:
- not specified
- Remarks on result:
- positive indication of irritation
- Irritant / corrosive response data:
- Corrosive effects were observed
- Interpretation of results:
- Category 1 (irreversible effects on the eye) based on GHS criteria
- Conclusions:
- 1-[(4-chlorophenyl)(phenyl)methyl]piperazine was estimated to be corrosive to the eyes of New Zealand White rabbits.
- Executive summary:
The ocular irritation potential of 1-[(4-chlorophenyl)(phenyl)methyl]piperazine was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor.
1-[(4-chlorophenyl)(phenyl)methyl]piperazine was estimated to be corrosive to the eyes of New Zealand White rabbits.
Based on the estimated result;1-[(4-chlorophenyl)(phenyl)methyl]piperazine can be considered corrosive to the eyes and can be classified under the category “Category 1” as per CLP regulation.
Reference
Estimation
method: Takes mode value from the 6 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 (
not "m")
)
)
and "n" )
and ("o"
and (
not "p")
)
)
and ("q"
and (
not "r")
)
)
and "s" )
and "t" )
and ("u"
and "v" )
)
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 Halogens AND Non-Metals by
Groups of elements
Domain
logical expression index: "g"
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: "h"
Referential
boundary: The
target chemical should be classified as Group 14 - Carbon C AND Group 15
- Nitrogen N AND Group 17 - Halogens Cl AND Group 17 - Halogens
F,Cl,Br,I,At by Chemical elements
Domain
logical expression index: "i"
Referential
boundary: The
target chemical should be classified as Group 16 - Oxygen O by Chemical
elements
Domain
logical expression index: "j"
Referential
boundary: The
target chemical should be classified as Group 14 - Carbon C AND Group 15
- Nitrogen N AND Group 17 - Halogens Cl AND Group 17 - Halogens
F,Cl,Br,I,At by Chemical elements
Domain
logical expression index: "k"
Referential
boundary: The
target chemical should be classified as Group 16 - Sulfur S OR Group 17
- Halogens F by Chemical elements
Domain
logical expression index: "l"
Referential
boundary: The
target chemical should be classified as Amine AND Aromatic compound AND
Aryl chloride AND Aryl halide AND Halogen derivative AND Heterocyclic
compound AND Secondary aliphatic amine AND Secondary amine AND Tertiary
aliphatic amine AND Tertiary amine by Organic functional groups, Norbert
Haider (checkmol)
Domain
logical expression index: "m"
Referential
boundary: The
target chemical should be classified as Aminal OR Anion OR Azo compound
OR Carboxylic acid amidine OR Cation OR CO2 derivative (general) OR
Guanidine OR Nitrile OR No functional group found OR Primary aliphatic
amine OR Primary amine by Organic functional groups, Norbert Haider
(checkmol)
Domain
logical expression index: "n"
Similarity
boundary:Target:
Clc1ccc(C(c2ccccc2)N2CCNCC2)cc1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization
Domain
logical expression index: "o"
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 by Skin
irritation/corrosion Exclusion rules by BfR
Domain
logical expression index: "p"
Referential
boundary: The
target chemical should be classified as Group All log Kow > 9 by Skin
irritation/corrosion Exclusion rules by BfR
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 Amidine by Organic Functional
groups
Domain
logical expression index: "s"
Referential
boundary: The
target chemical should be classified as Does NOT Biodegrade Fast by
Biodeg probability (Biowin 2) ONLY
Domain
logical expression index: "t"
Referential
boundary: The
target chemical should be classified as Biodegrades Fast by Biodeg
probability (Biowin 1) ONLY
Domain
logical expression index: "u"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= 0.523
Domain
logical expression index: "v"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 7.42
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (irreversible damage)
Respiratory irritation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Skin Irritation:
Several studies were performed to ascertain the degree of dermal irritation caused by 1-[(4-chlorophenyl)(phenyl)methyl]piperazine in living organisms. These studies include in vivo studies in rabbits as well as predicted data for the target chemical as well its functionally similar read across substances, 1-Phenylpiperazine[CAS: 92-54-6] and 1-methyl-3 -phenylpiperazine[CAS: 5271-27-2]. Thepredicted 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 for1-[(4-chlorophenyl)(phenyl)methyl]piperazine.1-[(4-chlorophenyl)(phenyl)methyl]piperazine was corrosive to New Zealand White rabbit skin.
Skin irritation effects were also estimated by four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra used within Danish QSAR database for 1-[(4-chlorophenyl)(phenyl)methyl]piperazine. Based on estimation, severe skin irritation effects were known when 1-[(4-chlorophenyl)(phenyl)methyl]piperazine was exposed to rabbit skin.Hence,1-[(4-chlorophenyl)(phenyl)methyl]piperazine can be considered severely irritating to skin.
Both the estimated results indicate a possibility of 1-[(4-chlorophenyl)(phenyl)methyl]piperazine being irritating to skin.
These results are supported by the experimental study summarized in American Industrial Hygiene Association Journal, 1962, 23:2, 95-107; for the functionally similar read across substance, 1-Phenylpiperazine[CAS: 92-54-6]. Primary skin irritation on rabbits was recorded in a 10-grade ordinal series and was based upon the severest reaction that develops on the clipped abdominal skin of each of five albino rabbits within 24 hours of the uncovered application of 0.01 ml of undiluted sample or of solutions in water, propylene glycol, or acetone. Grade 1 indicates no irritation and Grade 2 the least visible capillary injection from the undiluted chemical. Grade 6 indicates necrosis when undiluted and Grade 10 indicates necrosis from a 0.01% solution. Primary Irritation score after 24 hours for 1-phenyl piperazine was Grade 6.
Based on this grade,1-phenyl piperazine can be considered moderately irritating to rabbit skin.
The above results are further supported by the experimental study summarized in ATLA, 37, 671–689, 2009; for thefunctionally similar read across substance, 1-methyl-3-phenylpiperazine[CAS: 5271-27-2]. 1-methyl-3-phenylpiperazine was exposed to rabbit skin and observed for signs of irritation (no further details mentioned). Erythema was observed when1-methyl-3 -phenylpiperazine was applied to rabbit skin.The Primary Irritation Index was 3.3.
Hence,1-methyl-3-phenylpiperazine can be considered to be irritating to skin.
Based on the available data for the target as well as read across chemicals and applying the weight of evidence approach,1-[(4-chlorophenyl)(phenyl)methyl]piperazinecan be considered to be irritating to skin. Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Category 2”.
Eye Irritation:
Several studies were performed to ascertain the degree of ocular irritation caused by1-[(4-chlorophenyl)(phenyl)methyl]piperazinein living organisms. These studies include in vivo studies in rabbits as well as predicted data for the target chemical as well its functionally similar read across substances, Piperazine[CAS: 110-85-0] and 1-phenylpiperazine[CAS: 92-54 -6]. 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 1-[(4-chlorophenyl)(phenyl)methyl]piperazine.1-[(4-chlorophenyl)(phenyl)methyl]piperazine was corrosive to New Zealand White rabbit eyes.
This is supported by the experimental study summarized inAmerican Journal of Ophthalmology, 29, 1363–1372, 1946; for the functionally similar read across substance, Piperazine[CAS: 110-85-0].Normal rabbit eyes were selected on basis of visual inspection after staining with a 5% aqueous solution of fluorescein, and flushed out with distilled water 20 seconds after application. After a 2-hour resting period, 0.005 ml of a 5% solution was applied to the centre of the cornea while the lids were retracted. About one minute later the lids were released, and 18-24 hours later the eyes were stained with fluorescein and the injury scored.
Together with sulphuric acid and ammonium hydroxide, piperazine was given the grade 9 on a scale ranging from 1 to 10, with necrosis covering 60-90% of the cornea. An aqueous solution containing 1-5% piperazine (assumingly piperazine base) caused etching and necrosis of the rabbit cornea.
Hence piperazine was considered to be corrosive to rabbit eyes.
These results are supported by the experimental study summarized in American Industrial Hygiene Association Journal, 1962, 23:2, 95-107; for the functionally similar read across substance, 1-phenylpiperazine[CAS: 92-54-6]. Eye injury in rabbits is recorded in a 10- grade ordinal series and is based upon the degree of corneal necrosis that results from instillation of various volumes and concentrations of chemical.
Grade 1 indicates at most a very small area of necrosis resulting from 0.5 ml of undiluted chemical in the eye. Grade 5 indicates a so-called severe burn from 0.005 ml, and Grade 10 indicates a severe burn from 0.5 ml of a 1% solution in water or propylene glycol.
Primary Irritation score after 24 hours for 1-phenyl piperazine was Grade 9.
In the acute eye irritation study conducted in albino rabbits, 1-phenyl piperazine was considered to be corrosive to rabbit eyes.
Based on the available data for the target as well as read across chemicals and applying the weight of evidence approach,1-[(4-chlorophenyl)(phenyl)methyl]piperazine can be considered to be corrosive to skin. Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Category 1”.
Justification for classification or non-classification
Available data for 1-[(4-chlorophenyl)(phenyl)methyl]piperazine indicates that it is likely to cause severe irritation (corrosion) to skin and eyes.Hence,1-[(4-chlorophenyl)(phenyl)methyl]piperazine can be classified under the category “Category 2” for skin irritation and " Category 1" for eye irritation as per CLP regulation.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.