Registration Dossier
Registration Dossier
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: 254-529-9 | CAS number: 39577-43-0
- 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 833 mg/kg bw when rats were orally exposed with 1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine.
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:
- OECD Guideline 401 (Acute Oral Toxicity)
- Principles of method if other than guideline:
- Prediction is done using QSAR Toolbox version 3.3
- GLP compliance:
- not specified
- Test type:
- standard acute method
- Limit test:
- no
- Specific details on test material used for the study:
- - Name of test material: 1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine
- Molecular formula: C13H18Cl2N2
- Molecular weight: 273.205 g/mole
- Smiles notation: N1(c2cc(Cl)ccc2)CCN(CC1)CCCCl
- InChl: 1S/C13H18Cl2N2/c14-5-2-6-16-7-9-17(10-8-16)13-4-1-3-12(15)11-13/h1,3-4,11H,2,5-10H2
- Substance type: Organic
- Physical state: Solid - Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on oral exposure:
- No data available
- Doses:
- 833 mg/kg bw
- No. of animals per sex per dose:
- 5
- Control animals:
- yes
- Details on study design:
- No data available
- Statistics:
- No data available
- Preliminary study:
- No data available
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- 833 mg/kg bw
- Based on:
- test mat.
- Remarks on result:
- other: 50 % mortality observed
- Mortality:
- No data available
- Clinical signs:
- other: No data available
- Gross pathology:
- No data available
- Other findings:
- No data available
- Interpretation of results:
- Category 4 based on GHS criteria
- Conclusions:
- LD50 was estimated to be 833 mg/kg bw when rats were orally exposed with 1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine.
- 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 1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine. The LD50 was estimated to be 833 mg/kg bw when rats were orally exposed with 1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine.
Reference
The
prediction was based on dataset comprised from the following
descriptors: LD50
Estimation method: Takes average value from the 6 nearest neighbours
Domain logical expression:Result: In Domain
(((((((((("a"
or "b" or "c" or "d" )
and ("e"
and (
not "f")
)
)
and "g" )
and ("h"
and (
not "i")
)
)
and ("j"
and (
not "k")
)
)
and "l" )
and "m" )
and ("n"
and (
not "o")
)
)
and ("p"
and (
not "q")
)
)
and ("r"
and "s" )
)
Domain
logical expression index: "a"
Referential
boundary: The
target chemical should be classified as Aliphatic Amines by US-EPA New
Chemical Categories
Domain
logical expression index: "b"
Referential
boundary: The
target chemical should be classified as SN1 OR SN1 >> Iminium Ion
Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines
OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >>
Tertiary aromatic amine OR SN2 OR SN2 >> SN2 at an sp3 Carbon atom OR
SN2 >> SN2 at an sp3 Carbon atom >> Aliphatic halides by DNA binding by
OECD ONLY
Domain
logical expression index: "c"
Referential
boundary: The
target chemical should be classified as SN2 OR SN2 >> Nucleophilic
substitution at sp3 carbon atom OR SN2 >> Nucleophilic substitution at
sp3 carbon atom >> Alkyl halides by Protein binding by OASIS v1.3 ONLY
Domain
logical expression index: "d"
Referential
boundary: The
target chemical should be classified as SN2 OR SN2 >> SN2 reaction at
sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl
halides by Protein binding by OECD ONLY
Domain
logical expression index: "e"
Referential
boundary: The
target chemical should be classified as No alert found by DNA binding by
OASIS v.1.3
Domain
logical expression index: "f"
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 OR AN2 >>
Schiff base formation >> Polarized Haloalkene Derivatives 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 AN2 >> Shiff base formation for
aldehydes >> Haloalkane Derivatives with Labile Halogen OR AN2 >>
Thioacylation via nucleophilic addition after cysteine-mediated
thioketene formation OR AN2 >> Thioacylation via nucleophilic addition
after cysteine-mediated thioketene formation >> Polarized Haloalkene
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 >>
Generation of reactive oxygen species OR Radical >> Generation of
reactive oxygen species >> N,N-Dialkyldithiocarbamate Derivatives OR
Radical >> Generation of reactive oxygen species >> Thiols OR Radical >>
Generation of ROS by glutathione depletion (indirect) OR Radical >>
Generation of ROS by glutathione depletion (indirect) >> Haloalkanes
Containing Heteroatom 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) >> Haloalcohols OR Radical >> Radical
mechanism via ROS formation (indirect) >> N-Hydroxylamines OR Radical >>
Radical mechanism via ROS formation (indirect) >> Nitrophenols,
Nitrophenyl Ethers and Nitrobenzoic Acids 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 SN1 >> Nucleophilic
attack after reduction and nitrenium ion formation OR SN1 >>
Nucleophilic attack after reduction and nitrenium ion formation >>
Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids 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 >> Haloalkane Derivatives with Labile Halogen
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 by epoxide
metabolically formed after E2 reaction OR SN2 >> Alkylation by epoxide
metabolically formed after E2 reaction >> Haloalcohols OR SN2 >>
Alkylation by epoxide metabolically formed after E2 reaction >>
Monohaloalkanes 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 >> Haloalkane Derivatives with Labile Halogen OR SN2 >>
Alkylation, nucleophilic substitution at sp3-carbon atom >>
Monohaloalkanes OR SN2 >> Alkylation, nucleophilic substitution at
sp3-carbon atom >> Sulfonates and Sulfates OR SN2 >> Direct acting
epoxides formed after metabolic activation OR SN2 >> Direct acting
epoxides formed after metabolic activation >> Quinoline Derivatives OR
SN2 >> DNA alkylation OR SN2 >> DNA alkylation >> Alkylphosphates,
Alkylthiophosphates and Alkylphosphonates 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
after carbenium ion formation OR SN2 >> Nucleophilic substitution after
carbenium ion formation >> Monohaloalkanes OR SN2 >> Nucleophilic
substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at
sp3 Carbon atom >> Haloalkanes Containing Heteroatom 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 at sp3 and activated sp2 carbon atom OR SN2 >> SN2 at sp3 and
activated sp2 carbon atom >> Polarized Haloalkene Derivatives 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: "g"
Referential
boundary: The
target chemical should be classified as SN1 AND SN1 >> Iminium Ion
Formation AND SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines
AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >>
Tertiary aromatic amine AND SN2 AND SN2 >> SN2 at an sp3 Carbon atom AND
SN2 >> SN2 at an sp3 Carbon atom >> Aliphatic halides by DNA binding by
OECD ONLY
Domain
logical expression index: "h"
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: "i"
Referential
boundary: The
target chemical should be classified as High reactive OR High reactive
>> Benzyl halides OR Low reactive OR Low reactive >> N-substituted
aromatic amides OR Low reactive >> Primary haloalkanes OR Moderate
reactive OR Moderate reactive >> Five-membered heterocyclic urea by DPRA
Cysteine peptide depletion
Domain
logical expression index: "j"
Referential
boundary: The
target chemical should be classified as Non binder, without OH or NH2
group by Estrogen Receptor Binding
Domain
logical expression index: "k"
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 OR
Strong binder, OH group OR Weak binder, OH group by Estrogen Receptor
Binding
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"
Similarity
boundary:Target:
ClCCCN1CCN(c2cccc(Cl)c2)CC1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization
Domain
logical expression index: "n"
Referential
boundary: The
target chemical should be classified as Not categorized by Repeated dose
(HESS)
Domain
logical expression index: "o"
Referential
boundary: The
target chemical should be classified as Aliphatic amines (Mucous
membrane irritation) Rank C OR Aliphatic nitriles (Hepatotoxicity) Rank
B OR Allyl esters (Hepatotoxicity) Rank A OR Anilines (Hemolytic anemia
with methemoglobinemia) Rank A OR Anilines (Hepatotoxicity) Rank C OR
Chlorphentermine (Hepatotoxicity) Alert by Repeated dose (HESS)
Domain
logical expression index: "p"
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: "q"
Referential
boundary: The
target chemical should be classified as Esters of organic sulfonic or
sulfuric esters OR Ketones by Skin irritation/corrosion Inclusion rules
by BfR
Domain
logical expression index: "r"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= 1.94
Domain
logical expression index: "s"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 4.43
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 833 mg/kg bw
- Quality of whole database:
- Data is Klimisch 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, 1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine has 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 1-(3-chlorophenyl)-4-(3-chloropropyl)piperazinealong with the study available on structurally similar read across substance Trazodone (CAS no 19794-93-5). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.
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 1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine. The LD50 was estimated to be 833 mg/kg bw when rats were orally exposed with 1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine.
In another prediction done by SSS (2017) using the Danish QSAR with log kow as the primary descriptor, the acute oral toxicity was estimated for 1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine. The LD50 was estimated to be 660 mg/kg bw when mice were orally exposed with 1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine.
Also it is further supported by experimental study summarized by U.S. National Library of Medicine (ChemIDplusA TOXNET Database, 2017) on structurally similar read across substance Trazodone (CAS no 19794-93-5), mice and rat were treated with Trazodone orally. 50% mortality was observed in treated mice at 610 mg/kg bw and in rat at 690 mg/kg bw. Dyspnea of Lungs, Thorax or Respiration was observed. Convulsions or Effect on Seizure Threshold and Somnolence (General Depressed Activity) were observed in treated mice and rat. Therefore, LD50 was considered to 610 mg/kg bw and 690 mg/kg bw when mice and rat were treated with Trazodone orally.
Thus, based on the above studies and predictions on 1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine and its read across substances and by applying weight of evidence, it can be concluded that LD50 value is less than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine can be classified as Category IV of acute oral toxicity.
Justification for classification or non-classification
Based on the above studies and predictions on 1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine and its read across substances and by applying weight of evidence, it can be concluded that LD50 value is less than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine can be classified as Category IV of acute oral toxicity.
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.

EU Privacy Disclaimer
This website uses cookies to ensure you get the best experience on our websites.