4-chloro-1-methylpiperidinium chloride

Endpoint summary

Description of key information

Acute oral toxicity

LD50 was estimated to be 2230.54mg/kg bw, when male Carworth-Wistar rats were exposed with 4-chloro-1-methylpiperidin-1-ium chloride (5382-23-0) orally.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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 from OECD QSAR toolbox v3.3 and the QMRF report has been attached.

Qualifier:

equivalent or similar to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.3, 2017

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Specific details on test material used for the study:

- Name of test material: 4-chloro-1-methylpiperidinium chloride
- IUPAC name: 4-chloro-1-methylpiperidin-1-ium chloride
- Molecular formula: C6H13Cl2N
- Molecular weight: 170.0817 g/mole
- Smiles : CN1CCC(CC1)Cl.Cl
- Inchl: 1S/C6H12ClN.ClH/c1-8-4-2-6(7)3-5-8;/h6H,2-5H2,1H3;1H
- Substance type: Organic
- Physical state: Solid crystal powder (White - Slightly pale yellow)

Species:

rat

Strain:

other: Carworth-Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

No data available

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

No data available

Doses:

2230.54 mg/kg bw

No. of animals per sex per dose:

5 male

Control animals:

not specified

Details on study design:

No data available

Statistics:

No data available

Preliminary study:

No data available

Sex:

male

Dose descriptor:

LD50

Effect level:

2 230.54 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality was observed

Mortality:

No data available

Clinical signs:

other: No data available

Gross pathology:

No data available

Other findings:

No data available

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 8 nearest neighbours
Domain  logical expression:Result: In Domain

((((((((((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and ("m" and ( not "n") )  )  and "o" )  and ("p" and ( not "q") )  )  and ("r" and ( not "s") )  )  and ("t" and ( not "u") )  )  and ("v" and ( not "w") )  )  and "x" )  and ("y" and "z" )  )

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 SN2 AND SN2 >> SN2 at an sp3 Carbon atom AND SN2 >> SN2 at an sp3 Carbon atom >> Aliphatic halides by DNA binding by OECD

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as SN2 AND SN2 >> Nucleophilic substitution at sp3 carbon atom AND SN2 >> Nucleophilic substitution at sp3 carbon atom >> Alkyl halides  by Protein binding by OASIS v1.3

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as SN2 AND SN2 >> SN2 reaction at sp3 carbon atom AND SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl halides by Protein binding by OECD

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 >> 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 >> 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, 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 >> Direct acylation involving a leaving group OR SN2 >> Direct acylation involving a leaving group >> Acyl Halides 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 Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Moderate binder, NH2 group OR Moderate binder, OH grooup OR Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, non cyclic structure OR Strong binder, NH2 group OR Strong binder, OH group OR Weak binder, NH2 group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "i"

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: "j"

Referential boundary: The target chemical should be classified as Alpha aryloxy substituted acetic acid (9c) OR Known precedent reproductive and developmental toxic potential OR Piperazine-, dioxane-, morpholine-, tetrahydrothiopyran-like derivatives and cyclohexanamine (17c) OR Polyhalogenated benzene derivatives (8c) OR Toluene and small alkyl toluene derivatives (8a) by DART scheme v.1.0

Domain logical expression index: "k"

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: "l"

Referential boundary: The target chemical should be classified as Derivatives of alpha amino benzene OR Substituted indoles by Eye irritation/corrosion Inclusion rules by BfR

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 OR Metalloids by Groups of elements

Domain logical expression index: "o"

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

Domain logical expression index: "p"

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: "q"

Referential boundary: The target chemical should be classified as Group 16 - Oxygen O OR Group 16 - Sulfur S OR Group 17 - Halogens Br OR Group 17 - Halogens F OR Group 17 - Halogens I by Chemical elements

Domain logical expression index: "r"

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: "s"

Referential boundary: The target chemical should be classified as Primary and secondary aliphatic amines OR Tertiary aliphatic amine by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as No alert found by Respiratory sensitisation

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Pro-Schiff base formation OR Pro-Schiff base formation >> Pro-cross linking Schiff base OR Pro-Schiff base formation >> Pro-cross linking Schiff base >> Hexamine by Respiratory sensitisation

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Not classified by Oncologic Primary Classification

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Halogenated Aromatic Hydrocarbon Type Compounds OR ortho-Haloganated Heterocyclic Type Compounds by Oncologic Primary Classification

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Very fast by Bioaccumulation - metabolism half-lives ONLY

Domain logical expression index: "y"

Parametric boundary:The target chemical should have a value of log Kow which is >= -2.15

Domain logical expression index: "z"

Parametric boundary:The target chemical should have a value of log Kow which is <= -0.098

Interpretation of results:

other: not classified

Conclusions:

LD50 was estimated to be 2230.54mg/kg bw, when male Carworth-Wistar rats were exposed with 4-chloro-1-methylpiperidin-1-ium chloride (5382-23-0) orally.

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 4-chloro-1-methylpiperidin-1-ium chloride (5382-23-0).LD50 was estimated to be 2230.54mg/kg bw, when male Carworth-Wistar ratswere exposed with 4-chloro-1-methylpiperidin-1-ium chloride (5382-23-0) orally.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 230.54 mg/kg bw

Quality of whole database:

Data is Klimicsh 2 and from QSAR Toolbox 3.3. (2017)

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, 4-chloro-1-methylpiperidin-1-ium chloride (5382-23-0) 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 4-chloro-1-methylpiperidin-1-ium chloride (5382-23-0) 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 4-chloro-1-methylpiperidin-1-ium chloride (5382-23-0).LD50 was estimated to be 2230.54mg/kg bw, when male Carworth-Wistar rats were exposed with 4-chloro-1-methylpiperidin-1-ium chloride (5382-23-0) orally.

In another experimental study given by IFA GESTIS (GESTIS SUBSTANCE Database (information system in hazardous substance of the Berufsgenossenscheftn).2017)on structurally similar read across substance 1-Methylpiperazine(109-01-3).

Acute oral toxicity study was done in 5 Carworth-Wistar male rat using1-Methylpiperazine(109-01-3).All the animals having weight rang 90-120g and age 4-5 weeks and provided by Rockland rat diet, The test material in dose concentration 2560 given undiluted by oral intubation and observed for 14 days .50% mortality was observed at dose 2560mg/kg bw. HenceLD50 was considered to be 2560mg/kgbody weight. When rats were treated with1-Methylpiperazine(109-01-3)orally.

 

Also it is further supported by experimental study given by IFA GESTIS (GESTIS SUBSTANCE Database (information system in hazardous substance of the Berufsgenossenscheftn).2017)on structurally similar read across substance 1-(2-Aminoethyl)piperazine (140-31-8).Acute oral toxicity study was done in rat using 1-(2-Aminoethyl) piperazine (140-31-8).50% mortality was observed at dose 2110mg/kg bw. Hence LD50 was considered to be 2110mg/kg body weight. When rats were treated with1-(2-Aminoethyl)piperazine (140-31-8)orally.

Also it is further supported by experimental study given by RTECS (RTECS (registry of toxic effect of chemical substance data base), 2017) on structurally similar read across substance Chlorocyclohexane (542-18-7). Acute oral toxicity study was done in rat using Chlorocyclohexane (542-18-7). 50% mortality was observed at dose 3000mg/kg bw. Hence LD50 was considered to be 3000mg/kg body weight.

 

 

Thus, based on the above studies and predictions on 4-chloro-1-methylpiperidin-1-ium chloride (5382-23-0) and its read across substances, it can be concluded that LD50 value is 2230.54mg/kg bw.Thus, comparing this value with the criteria of CLP regulation 4-chloro-1-methylpiperidin-1-ium chloride (5382-23-0) can be “Not classified” for acute oral toxicity.

 

 

Justification for classification or non-classification

Thus, comparing this value with the criteria of CLP regulation 4-chloro-1-methylpiperidin-1-ium chloride (5382-23-0) can be “Not classified” for acute oral toxicity.