4-chloro-N-methylpiperidine

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

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:

The supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

The data is predicted using the OECD QSAR toolbox version 3.3

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material: 4-chloro-1-methylpiperidine
- Molecular formula: C6H12ClN
- Molecular weight: 133.621 g/mol
- Smiles notation: N1(CCC(CC1)Cl)C
- InChl: 1S/C6H12ClN/c1-8-4-2-6(7)3-5-8/h6H,2-5H2,1H3
- Substance type: Organic
- Physical state: Liquid

Radiolabelling:

not specified

Analytical monitoring:

not specified

Transformation products:

not specified

Key result

DT50:

92.616 d

Type:

(pseudo-)first order (= half-life)

Remarks on result:

other: Other details not known

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 "i" )  and ("j" and ( not "k") )  )  and "l" )  and ("m" and ( not "n") )  )  and ("o" and ( not "p") )  )  and ("q" and "r" )  )

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 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 >> 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 for aldehydes OR AN2 >> Shiff base formation for aldehydes >> Geminal Polyhaloalkane Derivatives OR Radical OR Radical >> Generation of reactive oxygen species OR Radical >> Generation of reactive oxygen species >> N,N-Dialkyldithiocarbamate Derivatives 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 SN2 OR SN2 >> Acylation involving a leaving group  OR SN2 >> Acylation involving a leaving group  >> Geminal Polyhaloalkane Derivatives OR SN2 >> Acylation involving a leaving group after metabolic activation OR SN2 >> Acylation involving a leaving group after metabolic activation >> Geminal Polyhaloalkane Derivatives OR SN2 >> Alkylation 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, nucleophilic substitution at sp3-carbon atom 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 after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives 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 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 calculated by Hydrolysis half-life (Kb, pH 7)(Hydrowin) ONLY

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Not calculated by Hydrolysis half-life (pH 6.5-7.4) ONLY

Domain logical expression index: "j"

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

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Aliphatic amines (Mucous membrane irritation) Rank C OR Thiocarbamates/Sulfides (Hepatotoxicity) No rank by Repeated dose (HESS)

Domain logical expression index: "l"

Similarity boundary:Target: CN1CCC(Cl)CC1
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Halogens AND Non-Metals by Groups of elements

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Alkali Earth by Groups of elements

Domain logical expression index: "o"

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: "p"

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

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of Molecular weight which is >= 73 Da

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of Molecular weight which is <= 160 Da

Validity criteria fulfilled:

not specified

Conclusions:

The estimated half-life of 4-chloro-1-methylpiperidine was estimated to be 92.6 days, indicating that it is not hydrolysable.

Executive summary:

Hydrolysis of 4-chloro-1-methylpiperidine (CAS no. 5570 -77 -4) is predicted using OECD QSAR toolbox version 3.3 with logKow as the primary descriptor. The estimated half-life of 4-chloro-1-methylpiperidine was estimated to be 92.6 days, indicating that it is not hydrolysable.

Description of key information

Hydrolysis of 4-chloro-1-methylpiperidine (CAS no. 5570 -77 -4) is predicted using OECD QSAR toolbox version 3.3 (2017) with logKow as the primary descriptor. The estimated half-life of 4-chloro-1-methylpiperidine was estimated to be 92.6 days, indicating that it is not hydrolysable.

Key value for chemical safety assessment

Half-life for hydrolysis:

92.6 d

Additional information

The predicted data for the target substance 4-chloro-1-methylpiperidine and the available data for its structurally similar substance were reviewed for hydrolysis endpoint and are presented as weight of evidence approach as follows:

Hydrolysis of 4-chloro-1-methylpiperidine (CAS no. 5570 -77 -4) is predicted using OECD QSAR toolbox version 3.3 (2017) with logKow as the primary descriptor. The estimated half-life of 4-chloro-1-methylpiperidine was estimated to be 92.6 days, indicating that it is not hydrolysable.

As part of a study in which the structurally similar substance 1-ethenylpyrrolidin-2-one (CAS 88 -12 -0) was administered in drinking water, 1-ethenylpyrrolidin-2-one was shown to be stable in drinking water for at least 4 days. Hence it can be considered that the test substance is slowly hydrolysable in water.

Considering above data it can be assumed that the target substance 4-chloro-1-methylpiperidine is slowly to negligibly hydrolysable and stable in water.