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Description of key information

Skin Irritation:

The dermal irritation potential of 1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine was estimated to be not irritating to the skin of New Zealand White rabbits.

Based on the estimated results, sodium benzenesulfinate can be considered not irritating to skin and can be classified under the category “Not Classified” as per CLP regulation.

Eye Irritation:

The ocular irritation potential of 1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine was estimated to be not irritating to the eyes of Himalayan rabbits.

Based on the estimated results, 1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine can be considered not irritating to eyes and can be classified under the category “Not Classified” as per CLP regulation.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
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 v3.3
GLP compliance:
not specified
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/mol
- 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:
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:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
0.5ml
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3
Details on study design:
no data available
Other effects / acceptance of results:
no data available
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
72 h
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No irritation observed

Estimation method: Takes mode value from the 7 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 ( not "m") )  )  and ("n" and ( not "o") )  )  and "p" )  and "q" )  and "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 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 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 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) >> 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 >> 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 >> 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 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 Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "i"

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: "j"

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: "k"

Referential boundary: The target chemical should be classified as Ketones by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael type addition to activated double bond of pyrimidine bases OR AN2 >> Michael type addition to activated double bond of pyrimidine bases >> Pyrimidines and Purines OR AN2 >> Shiff base formation with carbonyl group of pyrimidine or purine bases OR AN2 >> Shiff base formation with carbonyl group of pyrimidine or purine bases >> Pyrimidines and Purines by Protein binding alerts for Chromosomal aberration by OASIS v1.1

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"

Similarity boundary:Target: ClCCCN1CCN(c2cccc(Cl)c2)CC1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "q"

Similarity boundary:Target: ClCCCN1CCN(c2cccc(Cl)c2)CC1
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "r"

Similarity boundary:Target: ClCCCN1CCN(c2cccc(Cl)c2)CC1
Threshold=40%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "s"

Similarity boundary:Target: ClCCCN1CCN(c2cccc(Cl)c2)CC1
Threshold=50%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Aliphatic amines (Mucous membrane irritation) Rank C OR Allyl esters (Hepatotoxicity) Rank A OR Anilines (Hemolytic anemia with methemoglobinemia) Rank A OR Anilines (Hepatotoxicity) Rank C OR Halobenzenes (Hepatotoxicity) Rank A OR Halobenzenes (Renal toxicity) Rank A OR Halogenated aliphatic compounds (Hepatotoxicity) Rank A by Repeated dose (HESS)

Domain logical expression index: "v"

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: "w"

Referential boundary: The target chemical should be classified as Known precedent reproductive and developmental toxic potential OR Purine and pyrimidine-like derivatives (7b) OR Toluene and small alkyl toluene derivatives (8a) by DART scheme v.1.0

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Does NOT Biodegrade Fast by Biodeg probability (Biowin 7) ONLY

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Discrete chemical by Substance Type ONLY

Domain logical expression index: "z"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.394

Domain logical expression index: "aa"

Parametric boundary:The target chemical should have a value of log Kow which is <= 6.67

Interpretation of results:
other: not irritating
Conclusions:
1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine was estimated to be not irritating to the skin of New Zealand White rabbits.
Executive summary:

The dermal irritation potential of 1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine was estimated to be not irritating to the skin of New Zealand White rabbits.

Based on the estimated results, sodium benzenesulfinate can be considered not irritating to skin and can be classified under the category “Not Classified” as per CLP regulation.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification
Justification for type of information:
data is from OECD QSAR toolbox 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 test material: 1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine
- Molecular formula: C13H18Cl2N2
- Molecular weight: 273.205 g/mol
- 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:
rabbit
Strain:
Himalayan
Details on test animals or tissues and environmental conditions:
no data
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
0.1g
Duration of treatment / exposure:
single exposure
Observation period (in vivo):
1,24,48 and 72 hours
Duration of post- treatment incubation (in vitro):
no data
Number of animals or in vitro replicates:
3
Details on study design:
no data available
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 1,24,48 and 72 hours
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
no irritation observed

Estimation method: Takes mode value from the 5 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 ("o" and ( not "p") )  )  and "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 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 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 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 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 >> 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 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 Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "i"

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: "j"

Referential boundary: The target chemical should be classified as Inclusion rules not met by Eye irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Pyrrolidones by Eye irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "m"

Similarity boundary:Target: ClCCCN1CCN(c2cccc(Cl)c2)CC1
Threshold=40%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "n"

Similarity boundary:Target: ClCCCN1CCN(c2cccc(Cl)c2)CC1
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by Keratinocyte gene expression

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as High gene expression OR High gene expression >> Activated esters OR High gene expression >> N-Acylamides OR Very high gene expression OR Very high gene expression >> alpha-Halobenzyls by Keratinocyte gene expression

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Not calculated by Hydrolysis half-life (Kb, pH 7)(Hydrowin) ONLY

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.73

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.01

Interpretation of results:
other: not irritating
Conclusions:
1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine was estimated to be not irritating to the eyes of Himalayan rabbits.
Executive summary:

The ocular irritation potential of 1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine was estimated to be not irritating to the eyes of Himalayan rabbits.

Based on the estimated results, 1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine can be considered not irritating to eyes and can be classified under the category “Not Classified” as per CLP regulation.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin Irritation:

In different studies, 1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine has been investigated for potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with predicted data for target chemical 1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine and its closely related read across substances, 2-piperazin-1 -ylethanol [CAS: 103-76-4] andtriallyl isocyanurate [CAS:1025-15-6]. 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 dermal irritation potential was estimated for 1-(3-chlorophenyl)-4-(3 -chloropropyl)piperazine. 1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine was estimated to be not irritating to the skin of New Zealand White rabbits.

This result is supported by the experimental study summarized inAmerican Industrial Hygiene Association Journal, 1962, 23:2, 95-107, for theclosely related read across substance, 2 -piperazin-1-ylethanol [CAS: 103-76-4].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 forN-(2-Hydroxyethyl)piperazine was Grade 1.

Based on this grade,N-(2-Hydroxyethyl)piperazine can be considered not irritating to rabbit skin.

The above results are also supported by the experimental study summarized inTOXICOLOGICAL SUMMARY FOR TRIALLYL ISOCYANURATE [1025-15-6],National Institute of Environmental Health Sciences (NIEHS), 2009; for the closely related read across substanceTriallyl isocyanurate[1025-15-6].Triallyl isocyanurate was applied to intact (A), occluded (B) and abraded skin (C) of 3 rabbits (1/method).The chemical was applied 3 times over 3 days and observed for 14 days for signs of irritation.Repeated, prolonged contact of triallyl isocyanurate was essentially not irritating to rabbit skin.Hence, triallyl isocyanurate can be considered not 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-(3-chlorophenyl)-4-(3-chloropropyl)piperazine can be considered not irritating to skin.Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Not Classified”.

Eye Irritation:

In different studies, 1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine has been investigated for potential for ocular irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with predicted data for target chemical 1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine and its closely related read across substances,N,N diethylaniline[CAS: 91-66-7];2-{2-ethoxy-5-[(4-ethylpiperazin-1-yl)sulfonyl]phenyl}-5-methyl-7-propylimidazo[5,1-f][1,2,4]triazin-4(1H)-one (Vardenafil) [CAS: 224785-90-4].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-(3-chlorophenyl)-4-(3 -chloropropyl)piperazine. 1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine was estimated to be not irritating to the eyes of Himalayan rabbits.

This result is supported by the experimental study summarized inGESTIS, 2017; for the closely related substance, N,N diethylaniline [CAS: 91-66-7]. Undiluted test substance N,N diethylaniline, did not induce any irritation to rabbit eyes. Hence N,N diethylaniline  can be considered as a non irritant.

The above results are also supported by the experimental study summarized in PHARMACOLOGY/TOXICOLOGY NDA REVIEW AND EVALUATION, APPLICATION NUMBER:200179Orig1s000, 2010;for the closely related substance,2-{2-ethoxy-5-[(4-ethylpiperazin-1-yl)sulfonyl]phenyl}-5-methyl-7-propylimidazo[5,1-f][1,2,4]triazin-4(1H)-one (Vardenafil) [CAS: 224785-90-4]. A single application of 100 mg Vardenafil was instilled into a conjunctival sac of the right eyeof rabbits. The rabbits were observed and scored for signs of irritation 1 hour post dosing.Conjunctival redness (grade 1) and conjunctival chemosis (grade 1) was observed one hour post-dosing in rabbit eyes.

Vardenafil can be considered not irritating 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-(3-chlorophenyl)-4-(3-chloropropyl)piperazine can be considered not irritating to eyes.Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Not Classified”.

Justification for classification or non-classification

Available data for 1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine suggests that it is not likely to cause any irritation to eyes and skin.

1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine can be classified under the category “Not Classified” as per CLP regulation.