1-methylpiperidin-4-ol

Endpoint summary

Description of key information

Acute toxicity: oral
Acute oral LD50 value for the test substance 1-methylpiperidin-4-ol was estimated to be 2119 mg/kg bw for rats.

Acute toxicity: inhalation
The study does not needs to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of inhalable size.

Acute toxicity: dermal
Acute dermal LD50 value for the test substance 1-methylpiperidin-4-ol was estimated to be 2526.7 mg/kg bw for rabbits.

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 QSAR Toolbox 3.4. and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4

GLP compliance:

not specified

Test type:

other: No data

Specific details on test material used for the study:

- Name of test material (as cited in study report): 1-methylpiperidin-4-ol
- Molecular formula: C6H13NO
- Molecular weight: 115.175 g/mol
- Substance type: Organic
- Physical state: Liquid

Species:

rat

Strain:

not specified

Sex:

not specified

Route of administration:

oral: unspecified

Vehicle:

water

Details on oral exposure:

No data avaiable

Doses:

No data avaiable

No. of animals per sex per dose:

No data

Control animals:

not specified

Details on study design:

No data avaiable

Statistics:

No data avaiable

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

2 119 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50 % mortality observed

Mortality:

50 % mortality observed

Clinical signs:

No data avaiable

Body weight:

No data avaiable

Gross pathology:

No data avaiable

Other findings:

No data avaiable

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average 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("r" and(not "s")) ) and "t") and "u") and("v" and(not "w")) ) and "x") and("y" and(not "z")) ) and("aa" and(not "ab")) ) and "ac") and "ad") and "ae") and "af") and("ag" and "ah") )

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 Alcohol AND Piperidine AND Saturated heterocyclic amine AND Saturated heterocyclic fragment by Organic Functional groups

Domain logical expression index: "c"

Referential boundary:The target chemical should be classified as Alcohol AND Overlapping groups AND Piperidine AND Saturated heterocyclic amine AND Saturated heterocyclic fragment by Organic Functional groups (nested)

Domain logical expression index: "d"

Referential boundary:The target chemical should be classified as Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Amino, aliphatic attach [-N<] AND Hydroxy, aliphatic attach [-OH] by Organic functional groups (US EPA)

Domain logical expression index: "e"

Referential boundary:The target chemical should be classified as Alcohol AND Amine AND Heterocyclic compound AND Hydroxy compound AND Secondary alcohol AND Tertiary aliphatic amine AND Tertiary amine by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "f"

Referential boundary:The target chemical should be classified as No alert found by DNA binding by OASIS v.1.4

Domain logical expression index: "g"

Referential boundary:The target chemical should be classified as AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Flavonoids OR AN2 >>  Michael-type addition, quinoid structures >> Quinones and Trihydroxybenzenes OR AN2 >> Carbamoylation after isocyanate formation OR AN2 >> Carbamoylation after isocyanate formation >> N-Hydroxylamines OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds >> Four- and Five-Membered Lactones OR AN2 >> Nucleophilic addition reaction with cycloisomerization OR AN2 >> Nucleophilic addition reaction with cycloisomerization >> Hydrazine Derivatives OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> Dicarbonyl compounds 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 Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Acridone, Thioxanthone, Xanthone and Phenazine Derivatives OR Non-covalent interaction >> DNA intercalation >> Aminoacridine DNA Intercalators OR Non-covalent interaction >> DNA intercalation >> Coumarins OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide and Aminoalkylamine Side Chain OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Nitroaromatics OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Non-covalent interaction >> DNA intercalation >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives OR Non-covalent interaction >> DNA intercalation >> Quinolone Derivatives OR Non-covalent interaction >> DNA intercalation >> Quinones and Trihydroxybenzenes OR Radical 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 by ROS formation OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA >> Organic Peroxy Compounds OR Radical >> Radical mechanism by ROS formation >> Five-Membered Aromatic Nitroheterocycles OR Radical >> Radical mechanism by ROS formation >> Quinoxaline-Type 1,4-Dioxides OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Acridone, Thioxanthone, Xanthone and Phenazine Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> C-Nitroso Compounds OR Radical >> Radical mechanism via ROS formation (indirect) >> Conjugated Nitro Compounds OR Radical >> Radical mechanism via ROS formation (indirect) >> Coumarins OR Radical >> Radical mechanism via ROS formation (indirect) >> Diazenes and Azoxyalkanes OR Radical >> Radical mechanism via ROS formation (indirect) >> Flavonoids OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Nitroaromatics OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Hydrazine Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> N-Hydroxylamines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitro Azoarenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR Radical >> Radical mechanism via ROS formation (indirect) >> p-Substituted Mononitrobenzenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones and Trihydroxybenzenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Thiols OR Radical >> ROS formation after GSH depletion (indirect) OR Radical >> ROS formation after GSH depletion (indirect) >> Haloalcohols OR SN1 OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers OR SN1 >> Direct nucleophilic attack on diazonium cation (DNA alkylation) OR SN1 >> Direct nucleophilic attack on diazonium cation (DNA alkylation) >> Diazenes and Azoxyalkanes OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> N-Nitroso Compounds OR SN1 >> Nucleophilic attack after carbenium ion formation >> Pyrrolizidine Derivatives 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 >> Fused-Ring Primary Aromatic Amines OR SN1 >> Nucleophilic attack after nitrenium ion formation OR SN1 >> Nucleophilic attack after nitrenium ion formation >> N-Hydroxylamines OR SN1 >> Nucleophilic attack after nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN1 >> Nucleophilic attack after nitrosonium cation formation OR SN1 >> Nucleophilic attack after nitrosonium cation formation >> N-Nitroso Compounds OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Conjugated Nitro Compounds OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Fused-Ring Nitroaromatics OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitro Azoarenes OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> p-Substituted Mononitrobenzenes OR SN1 >> Nucleophilic substitution after glutathione-induced nitrenium ion formation OR SN1 >> Nucleophilic substitution after glutathione-induced nitrenium ion formation >> C-Nitroso Compounds OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> N-Hydroxylamines OR SN2 >> Acylation >> Specific Acetate Esters 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 OR SN2 >> Alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> Alkylation by epoxide metabolically formed after E2 reaction OR SN2 >> Alkylation by epoxide metabolically formed after E2 reaction >> Haloalcohols 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 and Sulfur 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 and Naphthalenediimide Derivatives OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Sulfonates and Sulfates OR SN2 >> Alkylation, ring opening SN2 reaction OR SN2 >> Alkylation, ring opening SN2 reaction >> Four- and Five-Membered Lactones OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Coumarins OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> Direct nucleophilic attack on diazonium cation OR SN2 >> Direct nucleophilic attack on diazonium cation >> Hydrazine Derivatives OR SN2 >> DNA alkylation 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 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-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers by DNA binding by OASIS v.1.4

Domain logical expression index: "h"

Referential boundary:The target chemical should be classified as 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 >> Sulfonylureas OR Michael addition OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems >> Furans 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 OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> 5-alkoxyindoles OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Alkyl phenols OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Methylenedioxyphenyl 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 Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated ketones 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 Schiff base formers >> Direct Acting Schiff Base Formers OR Schiff base formers >> Direct Acting Schiff Base Formers >> Mono aldehydes OR SN1 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Allyl benzenes OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Aromatic phenylureas OR SN1 >> Nitrenium Ion formation >> Primary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Secondary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Secondary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary (unsaturated) heterocyclic amine  OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN2 OR SN2 >> Episulfonium Ion Formation OR SN2 >> Episulfonium Ion Formation >> Mustards OR SN2 >> Epoxidation of Aliphatic Alkenes OR SN2 >> Epoxidation of Aliphatic Alkenes >> Halogenated polarised alkenes OR SN2 >> P450 Mediated Epoxidation OR SN2 >> P450 Mediated Epoxidation >> Thiophenes-SN2 OR SN2 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Aliphatic halides OR SN2 >> SN2 at an sp3 Carbon atom >> Alkyl carbamates OR SN2 >> SN2 at an sp3 Carbon atom >> Phosphates OR SN2 >> SN2 at an sp3 Carbon atom >> Sulfonates 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 OASIS v1.4

Domain logical expression index: "k"

Referential boundary:The target chemical should be classified as Acylation OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group >> Carboxylic Acid Amides OR Acylation >> Acylation involving an activated (glucuronidated) ester group OR Acylation >> Acylation involving an activated (glucuronidated) ester group >> Arenecarboxylic Acid Esters OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> Anhydrides (sulphur analogues of anhydrides)  OR Acylation >> Direct acylation involving a leaving group >> Carbamates  OR Acylation >> Direct acylation involving a leaving group >> Carboxylic Acid Amides OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR Acylation >> Ester aminolysis >> Dithiocarbamates OR Acylation >> Ester aminolysis or thiolysis OR Acylation >> Ester aminolysis or thiolysis >> Carbamates  OR Acylation >> Ring opening acylation OR Acylation >> Ring opening acylation >> beta-Lactams  OR AN2 OR AN2 >> Formaldehyde releaser (abiotic) OR AN2 >> Formaldehyde releaser (abiotic) >> Hexahydrotriazine Derivatives OR AN2 >> Michael addition to activated double bonds OR AN2 >> Michael addition to activated double bonds >> alpha,beta-Unsaturated Carbonyls and Related Compounds 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 >> Michael-type addition to activated double bonds in vinyl pyridines OR AN2 >> Michael-type addition to activated double bonds in vinyl pyridines >> Ethenyl Pyridines OR AN2 >> Michael-type addition to quinoid structures  OR AN2 >> Michael-type addition to quinoid structures  >> Carboxylic Acid Amides OR AN2 >> Michael-type addition to quinoid structures  >> N-Substituted Aromatic Amines OR AN2 >> Michael-type addition to quinoid structures  >> Substituted Anilines OR AN2 >> Michael-type addition to quinoid structures  >> Substituted Phenols OR AN2 >> Nucleophilic addition to pyridonimine tautomer of aminopyridoindoles or aminopyridoimidazoles (hypothesized) OR AN2 >> Nucleophilic addition to pyridonimine tautomer of aminopyridoindoles or aminopyridoimidazoles (hypothesized) >> Heterocyclic Aromatic Amines OR AN2 >> Schiff base formation with carbonyl group of pyrimidine and purine bases OR AN2 >> Schiff base formation with carbonyl group of pyrimidine and purine bases >> Pyrimidines and Purines OR Michael addition OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> alpha,beta-Carbonyl compounds with polarized double bonds  OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> Conjugated systems with electron withdrawing groups  OR Michael addition >> Michael addition on polarised Alkenes OR Michael addition >> Michael addition on polarised Alkenes >> Polarised Alkene - alkenyl pyridines, pyrazines, pyrimidines or triazines  OR Michael addition >> Michael addition on polarised Alkenes >> Polarised Alkenes - sulfones  OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones OR Radical reactions OR Radical reactions >> ROS Generation OR Radical reactions >> ROS Generation >> Sterically Hindered Piperidine Derivatives OR Radical reactions >> ROS generation and direct attack of hydroxyl radical to the C8 position of nucleoside base OR Radical reactions >> ROS generation and direct attack of hydroxyl radical to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines OR Schiff base formation OR Schiff base formation >> Direct acting Schiff base formers OR Schiff base formation >> Direct acting Schiff base formers >> 1,2-Dicarbonyls and 1,3-Dicarbonyls  OR Schiff base formation >> Schiff base formation with carbonyl compounds OR Schiff base formation >> Schiff base formation with carbonyl compounds >> Aromatic carbonyl compounds OR SE reaction (CYP450-activated heterocyclic amines) OR SE reaction (CYP450-activated heterocyclic amines) >> Direct attack of arylnitrenium cation to the C8 position of nucleoside base  OR SE reaction (CYP450-activated heterocyclic amines) >> Direct attack of arylnitrenium cation to the C8 position of nucleoside base  >> Heterocyclic Aromatic Amines OR SN2 OR SN2 >> Interchange reaction with sulphur containing compounds OR SN2 >> Interchange reaction with sulphur containing compounds >> Thiols and disulfide compounds  OR SN2 >> Nucleophilic substitution on benzilyc carbon atom OR SN2 >> Nucleophilic substitution on benzilyc carbon atom >> alpha-Activated benzyls  OR SN2 >> SN2 Reaction at a sp3 carbon atom OR SN2 >> SN2 Reaction at a sp3 carbon atom >> Activated alkyl esters and thioesters  OR SN2 >> SN2 reaction at a sulfur atom OR SN2 >> SN2 reaction at a sulfur atom >> Thiocyanates OR SN2 Ionic OR SN2 Ionic >> Nucleophilic substitution at protein disulfide bonds involving S-nucleophiles OR SN2 Ionic >> Nucleophilic substitution at protein disulfide bonds involving S-nucleophiles >> Thiourea compounds  OR SNAr OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds >> Activated aryl and heteroaryl compounds OR SR reaction (peroxidase-activated heterocyclic amines) OR SR reaction (peroxidase-activated heterocyclic amines) >> Direct attack of arylnitrenium radical to the C8 position of nucleoside base OR SR reaction (peroxidase-activated heterocyclic amines) >> Direct attack of arylnitrenium radical to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines by Protein binding by OASIS v1.4

Domain logical expression index: "l"

Referential boundary:The target chemical should be classified as No alert found by Protein binding by OECD

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 >> Acetates OR Michael addition OR Michael addition >> Quinones and Quinone-type Chemicals OR Michael addition >> Quinones and Quinone-type Chemicals >> Pyranones (and related nitrogen chemicals) OR SN2 OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Allyl acetates and related chemicals by Protein binding by OECD

Domain logical expression index: "n"

Referential boundary:The target chemical should be classified as Not possible to classify according to these rules (GSH) by Protein binding potency

Domain logical expression index: "o"

Referential boundary:The target chemical should be classified as Moderately reactive (GSH) OR Moderately reactive (GSH) >> 2-Vinyl carboxamides (MA) by Protein binding potency

Domain logical expression index: "p"

Referential boundary:The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "q"

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

Domain logical expression index: "r"

Referential boundary:The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "s"

Referential boundary:The target chemical should be classified as Group 15 - Phosphorus P OR Group 16 - Sulfur S OR Group 17 - Halogens Br OR Group 17 - Halogens Cl OR Group 17 - Halogens F OR Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "t"

Similarity boundary:Target: CN1CCC(O)CC1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "u"

Similarity boundary:Target: CN1CCC(O)CC1
Threshold=40%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "v"

Referential boundary:The target chemical should be classified as Stable form by Tautomers unstable

Domain logical expression index: "w"

Referential boundary:The target chemical should be classified as Lactim form by Tautomers unstable

Domain logical expression index: "x"

Referential boundary:The target chemical should be classified as weeks - months by Biodeg ultimate (Biowin 3) ONLY

Domain logical expression index: "y"

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: "z"

Referential boundary:The target chemical should be classified as Known precedent reproductive and developmental toxic potential OR Opioid receptor binders:Morphine- like derivatives (6a-1 to 6) OR Opioid receptor binders:Morphine- like derivatives (6a-1 to 6) >> Morphine- like derivatives OR Piperazine-, dioxane-, morpholine-, tetrahydrothiopyran-like derivatives and cyclohexanamine (17c) by DART scheme v.1.0

Domain logical expression index: "aa"

Referential boundary:The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CN Lipid Solubility < 0.4 g/kg by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "ab"

Referential boundary:The target chemical should be classified as Group All Melting Point > 200 C OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN log Kow > 4.5 by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "ac"

Similarity boundary:Target: CN1CCC(O)CC1
Threshold=50%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "ad"

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

Domain logical expression index: "ae"

Referential boundary:The target chemical should be classified as Narcotic Amine by Acute aquatic toxicity MOA by OASIS ONLY

Domain logical expression index: "af"

Referential boundary:The target chemical should be classified as Class 5 (Not possible to classify according to these rules) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "ag"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.591

Domain logical expression index: "ah"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.431

Interpretation of results:

GHS criteria not met

Conclusions:

Acute oral LD50 value for the test substance 1-methylpiperidin-4-ol was estimated to be 2119 mg/kg bw for rats.

Executive summary:

Based on the prediction done using the OECD QSAR toolbox version 3.4 considering the five closest read across substances, the acute oral toxicity was predicted for target substance 1-methylpiperidin-4-ol (CAS no. 106 -52 -5). LD50 value was estimated to be 2119 mg/kg bw for rats . Based on this value it can be concluded that the substance 1-methylpiperidin-4-ol is considered to be non-toxic to rats and does not classify under Acute oral toxic category as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 119 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from QSAR Toolbox 3.4 (2016)

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

Endpoint conclusion

Quality of whole database:

The study does not needs to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of inhalable size.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

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:

Prediction is done using QSAR Toolbox version 3.4 and the supporting QMRF report has been attached

Qualifier:

equivalent or similar to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4

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 (as cited in study report): 1-methylpiperidin-4-ol
- Molecular formula: C6H13NO
- Molecular weight: 115.175 g/mol
- Substance type: Organic
- Physical state: Liquid

Species:

rabbit

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

No data avaialble

Type of coverage:

not specified

Vehicle:

not specified

Details on dermal exposure:

No data avaialble

Duration of exposure:

24 hours

Doses:

No data

No. of animals per sex per dose:

No data

Control animals:

not specified

Details on study design:

No data avaialble

Statistics:

No data avaialble

Preliminary study:

No data avaialble

Sex:

not specified

Dose descriptor:

LD50

Effect level:

2 526.7 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50 % mortality observed

Mortality:

No data avaialble

Clinical signs:

No data avaialble

Body weight:

No data avaialble

Gross pathology:

No data avaialble

Other findings:

No data avaialble

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average 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 ("i" and ( not "j") )  )  and "k" )  and ("l" and ( not "m") )  )  and ("n" and ( not "o") )  )  and ("p" and ( not "q") )  )  and ("r" and ( not "s") )  )  and "t" )  and ("u" and ( not "v") )  )  and ("w" and "x" )  )

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 Alcohol AND Piperidine AND Saturated heterocyclic amine AND Saturated heterocyclic fragment by Organic Functional groups

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Alcohol AND Overlapping groups AND Piperidine AND Saturated heterocyclic amine AND Saturated heterocyclic fragment by Organic Functional groups (nested)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Amino, aliphatic attach [-N<] AND Hydroxy, aliphatic attach [-OH] by Organic functional groups (US EPA)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Alcohol AND Amine AND Heterocyclic compound AND Hydroxy compound AND Secondary alcohol AND Tertiary aliphatic amine AND Tertiary amine by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Iminium Ion Formation AND SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines by DNA binding by OECD

Domain logical expression index: "g"

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 Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes 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 by DNA binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as High (Class III) by Toxic hazard classification by Cramer (extension) ONLY

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for Chromosomal aberration by OASIS v.1.2

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Radical mechanism OR Radical mechanism >> ROS generation OR Radical mechanism >> ROS generation >> Sterically Hindered Piperidine Derivatives by Protein binding alerts for Chromosomal aberration by OASIS v.1.2

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr OR Group 15 - Phosphorus P by Chemical elements

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Phenol Type Compounds by Oncologic Primary Classification

Domain logical expression index: "p"

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: "q"

Referential boundary: The target chemical should be classified as High gene expression OR High gene expression >> N-Acylamides by Keratinocyte gene expression

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Aliphatic Amines by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Amides OR Nitriles, Polyaliphatic by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Class 5 (Not possible to classify according to these rules) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Not categorized by OECD HPV Chemical Categories

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Primary amines OR Secondary amines by OECD HPV Chemical Categories

Domain logical expression index: "w"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.38

Domain logical expression index: "x"

Parametric boundary:The target chemical should have a value of log Kow which is <= -0.0597

Interpretation of results:

not classified

Conclusions:

Acute dermal LD50 value for the test substance 1-methylpiperidin-4-ol was estimated to be 2526.7 mg/kg bw for rabbits.

Executive summary:

Based on the prediction done using the OECD QSAR toolbox version 3.4 considering the five closest read across substances, the acute dermal toxicity was predicted for target substance 1-methylpiperidin-4-ol (CAS no. 106 -52 -5). LD50 value was estimated to be 2526.7 mg/kg bw for rabbits . Based on this value it can be concluded that the substance 1-methylpiperidin-4-ol is considered to be non-toxic to rabbit and does not classify under Acute dermal toxic category as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no study available

Dose descriptor:

LD50

Value:

2 526.7 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from QSAR Toolbox 3.4 (2016)

Additional information

Acute toxicity: oral

Predicted data for the test chemical 4-Piperidinol, 1-methyl- (CAS No. 106-52-5) and the studies of its read across substances were reviewed to summarize the following information:

Based on the prediction done using the OECD QSAR toolbox version 3.4 considering the five closest read across substances, the acute oral toxicity was predicted for target substance 1-methylpiperidin-4-ol (CAS no. 106 -52 -5). LD50 value was estimated to be 2119 mg/kg bw for rats .

In supporting study for RA (CAS No.109-01-3), Acute oral toxicity of 1-methylpiperazine was studied in rats. 50 % mortality was observed in treated rats at 2560 mg/kg bw. Therefore, acute oral LD50 was determined to be 2560 mg/kg bw.

In a study given by European Chemicals Bureau IUCID Data set (2000) for read across (CAS 105-59-9), acute oral toxicity was evaluated in five Carworth–Wistar rats by using Ethanol, 2.2’-(methylimino)bis- (MDEA) in the concentration in a logarithmic series. 50 % mortality observed in treated rats at 4780 mg/kg bw. Therefore, LD50 was considered to be 4780 mg/kg bw when Carworth–Wistar rats were treated with Ethanol, 2.2’-(methylimino)bis- (MDEA) orally by gavage.

In the above similar IUCID Data set for read across (CAS 105-59-9), acute oral toxicity was evaluated in rats by using Ethanol, 2.2’-(methylimino)bis- (MDEA) in the concentration of 4680 mg/kg bw. 50 % mortality observed in treated rats at 4680 mg/kg bw. Therefore, LD50 was considered to be 4680 mg/kg bw when rats were treated with Ethanol, 2.2’-(methylimino)bis- (MDEA) orally.

Thus, based on weight of evidence for target 4-piperidinol, 1-methyl-(CAS no 106-52-5) and its structurally related read across substances, the target substance is likely to be non hazardous and does not classify under Acute oral toxic category as per CLP regulation.

Acute toxicity: inhalation

Acute toxicity: dermal
Predicted data for the test chemical 4-Piperidinol, 1-methyl- (CAS No. 106-52-5) and the studies of its read across substances were reviewed to summarize the following information:

Based on the prediction done using the OECD QSAR toolbox version 3.4 considering the five closest read across substances, the acute dermal toxicity was predicted for target substance 1-methylpiperidin-4-ol (CAS no. 106 -52 -5). LD50 value was estimated to be 2526.7 mg/kg bw for rabbits.

In a study given by European Chemicals Bureau IUCID Data set (2000) for read across (CAS 105-59-9), for dermal toxicity study, rabbits were treated with Ethanol, 2.2’-(methylimino)bis- (MDEA) in the concentration of 2000 mg/kg bw dermally. No mortality observed in treated rabbits. Sluggishness, unsteady gait, emaciation and prostration were observed after application of undiluted MDEA in treated rabbits but, surviving animals recovered during the observation period. Therefore, LD50 was considered to be > 2000 mg/kg bw when rabbits were treated with Ethanol, 2.2’-(methylimino)bis- (MDEA) dermally.

In the above similar IUCID Data set for read across (CAS 105-59-9), In dermal toxicity study,4 male New Zealand albino rabbits were treated with Ethanol, 2.2’-(methylimino)bis- (MDEA) in the concentration of 5990 mg/kg bw dermally. No mortality observed in treated rabbits. Therefore, LD50 was considered to be > 5990 mg/kg bw when 4 male New Zealand albino rabbits were treated with Ethanol, 2.2’-(methylimino)bis- (MDEA) dermally.

Thus, based on weight of evidence for target 4-piperidinol, 1-methyl-(CAS no 106-52-5) and its structurally related read across substances, the target substance is likely to be non hazardous and does not classify under Acute dermal toxic category as per CLP regulation.

Justification for classification or non-classification

Based on weight of evidence approach for target 4-piperidinol, 1-methyl-(CAS no 106-52-5) and its structurally related read across substances (CAS no 109 -01 -3 and 105-59-9) it is likely to be non hazardous for acute oral and dermal toxicity.