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EC number: 226-942-4 | CAS number: 5570-77-4
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Description of key information
Repeated dose toxicity: oral
Based on the prediction done using the
OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and
considering the five closest read across substances, repeated dose oral
toxicity was predicted for the test compound 4-Chloro-1-methylpiperidine
. The study assumed the use rats in repeated dose toxicity study. No
significant alterations were noted at the dose level of 557.61
mg/kg/day. The predicted No Observed Adverse Effect Level (NOAEL) for
4-Chloro-1-methylpiperidine is considered to be 557.61 mg/kg/day.
Repeated dose toxicity: inhalation
Since no compound related effects on rats are observed, the no observed effect concentration (NOEC) relating to repeated dose for the given test material 4-chloro-1-methylpiperidine is estimated to be 119210 mg/m3 via inhalation route of administration using QSAR Toolbox version 3.4.
Repeated dose toxicity: dermal
The acute toxicity
value for 4-chloro-1-methylpiperidine (as provided in section 7.2.3) is
>2000 mg/kg body weight. Also, given the use of the chemical; repeated
exposure by the dermal route is unlikely since the use of gloves is
common practice in industries. Thus, it is expected that
4-chloro-1-methylpiperidine shall not exhibit 28 day repeated dose
toxicity by the dermal route. In addition, there is no data available
that suggests that 4-chloro-1-methylpiperidine shall exhibit repeated
dose toxicity by the dermal route. Hence this end point was considered
for waiver.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- repeated dose toxicity: oral, other
- Type of information:
- (Q)SAR
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification
- Justification for type of information:
- Data is predicted by OECD QSAR Toolbox version 3.4. The supporting QMRF report has been attached
- Qualifier:
- according to guideline
- Guideline:
- other: as mentioned below
- Principles of method if other than guideline:
- Data is predicted by OECD QSAR Toolbox version 3.4.
- 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 - Species:
- rat
- Strain:
- not specified
- Sex:
- not specified
- Route of administration:
- oral: gavage
- Vehicle:
- not specified
- Analytical verification of doses or concentrations:
- not specified
- Frequency of treatment:
- No data
- Remarks:
- No data
- Control animals:
- not specified
- Clinical signs:
- no effects observed
- Mortality:
- not specified
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not specified
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Dose descriptor:
- NOAEL
- Effect level:
- 557.619 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- body weight and weight gain
- clinical signs
- Remarks on result:
- other: No toxic effect were observed.
- Critical effects observed:
- not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Conclusions:
- Since no compound related adverse effects on rats are observed, the no observed adverse effect level (NOAEL) relating to repeated dose for the given test material 4-chloro-1-methylpiperidine is estimated to be 557.61 mg/kg/day via oral route of administration using QSAR Toolbox version 3.4.
- Executive summary:
Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, repeated dose oral toxicity was predicted for the test compound 4-Chloro-1-methylpiperidine . The study assumed the use rats in repeated dose toxicity study. No significant alterations were noted at the dose level of 557.61 mg/kg/day. The predicted No Observed Adverse Effect Level (NOAEL) for 4-Chloro-1-methylpiperidine is considered to be 557.61 mg/kg/day.
Reference
The
prediction was based on dataset comprised from the following
descriptors: NOAEL
Estimation method: Takes average value from the 7 nearest neighbours
Domain logical expression:Result: In Domain
((((((((((((("a"
or "b" or "c" or "d" or "e" or "f" or "g" )
and ("h"
and (
not "i")
)
)
and ("j"
and (
not "k")
)
)
and ("l"
and (
not "m")
)
)
and "n" )
and ("o"
and (
not "p")
)
)
and "q" )
and "r" )
and ("s"
and (
not "t")
)
)
and ("u"
and (
not "v")
)
)
and ("w"
and (
not "x")
)
)
and ("y"
and (
not "z")
)
)
and ("aa"
and "ab" )
)
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 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
Domain
logical expression index: "c"
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: "d"
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 v1.4
Domain
logical expression index: "e"
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: "f"
Referential
boundary: The
target chemical should be classified as Narcotic Amine by Acute aquatic
toxicity MOA by OASIS
Domain
logical expression index: "g"
Referential
boundary: The
target chemical should be classified as Aliphatic Amines by Aquatic
toxicity classification by ECOSAR
Domain
logical expression index: "h"
Referential
boundary: The
target chemical should be classified as No alert found by DNA binding by
OASIS v.1.4
Domain
logical expression index: "i"
Referential
boundary: The
target chemical should be classified as Non-covalent interaction OR
Non-covalent interaction >> DNA intercalation OR Non-covalent
interaction >> DNA intercalation >> N-Hydroxyethyl Lactams 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 via
ROS formation (indirect) OR Radical >> Radical mechanism via ROS
formation (indirect) >> N,N-Dialkyldithiocarbamate Derivatives OR SN1 OR
SN1 >> Nucleophilic substitution after carbenium ion formation OR SN1 >>
Nucleophilic substitution after carbenium ion formation >>
Monohaloalkanes OR SN2 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 >>
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 and Sulfur Mustards 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 >> Monohaloalkanes 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 by
DNA binding by OASIS v.1.4
Domain
logical expression index: "j"
Referential
boundary: The
target chemical should be classified as Non binder, without OH or NH2
group by Estrogen Receptor Binding
Domain
logical expression index: "k"
Referential
boundary: The
target chemical should be classified as 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 by Estrogen Receptor Binding
Domain
logical expression index: "l"
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: "m"
Referential
boundary: The
target chemical should be classified as Ketones OR Primary and secondary
aliphatic amines by Skin irritation/corrosion Inclusion rules by BfR
Domain
logical expression index: "n"
Referential
boundary: The
target chemical should be classified as Bioavailable by Lipinski Rule
Oasis ONLY
Domain
logical expression index: "o"
Referential
boundary: The
target chemical should be classified as Halogens AND Non-Metals by
Groups of elements
Domain
logical expression index: "p"
Referential
boundary: The
target chemical should be classified as Metalloids by Groups of elements
Domain
logical expression index: "q"
Similarity
boundary:Target:
CN1CCC(Cl)CC1
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization
Domain
logical expression index: "r"
Similarity
boundary:Target:
CN1CCC(Cl)CC1
Threshold=40%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization
Domain
logical expression index: "s"
Referential
boundary: The
target chemical should be classified as Not categorized by Repeated dose
(HESS)
Domain
logical expression index: "t"
Referential
boundary: The
target chemical should be classified as Aliphatic amines (Mucous
membrane irritation) Rank C by Repeated dose (HESS)
Domain
logical expression index: "u"
Referential
boundary: The
target chemical should be classified as (!Undefined)Group All Lipid
Solubility < 0.01 g/kg AND (!Undefined)Group CNHal Lipid Solubility < 4
g/kg AND (!Undefined)Group CNHal Lipid Solubility < 400 g/kg by Skin
irritation/corrosion Exclusion rules by BfR
Domain
logical expression index: "v"
Referential
boundary: The
target chemical should be classified as Group All log Kow < -3.1 by Skin
irritation/corrosion Exclusion rules by BfR
Domain
logical expression index: "w"
Referential
boundary: The
target chemical should be classified as No alert found by Protein
binding alerts for skin sensitization by OASIS v1.4
Domain
logical expression index: "x"
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 >> Carbamates by Protein binding alerts for
skin sensitization by OASIS v1.4
Domain
logical expression index: "y"
Referential
boundary: The
target chemical should be classified as No alert found by in vivo
mutagenicity (Micronucleus) alerts by ISS
Domain
logical expression index: "z"
Referential
boundary: The
target chemical should be classified as Oxolane by in vivo mutagenicity
(Micronucleus) alerts by ISS
Domain
logical expression index: "aa"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= 0.0664
Domain
logical expression index: "ab"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 3.69
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 557.61 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Data is of K2 reliability and predicted by QSAR toolbox.
Repeated dose toxicity: inhalation - systemic effects
Link to relevant study records
- Endpoint:
- repeated dose toxicity: inhalation, other
- Type of information:
- (Q)SAR
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification
- Justification for type of information:
- Data is predicted by OECD QSAR Toolbox version 3.4. The supporting QMRF report has been attached
- Qualifier:
- according to guideline
- Guideline:
- other: as mentioned below
- Principles of method if other than guideline:
- Data is predicted by OECD QSAR Toolbox version 3.4.
- 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 - Species:
- rat
- Strain:
- not specified
- Sex:
- not specified
- Route of administration:
- inhalation
- Type of inhalation exposure:
- not specified
- Vehicle:
- not specified
- Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- not specified
- Frequency of treatment:
- not specified
- Remarks:
- no data
- Control animals:
- not specified
- Details on study design:
- not specified
- Positive control:
- not specified
- Observations and examinations performed and frequency:
- not specified
- Sacrifice and pathology:
- not specified
- Other examinations:
- not specified
- Statistics:
- not specified
- Clinical signs:
- no effects observed
- Mortality:
- not specified
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not specified
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Key result
- Dose descriptor:
- NOEC
- Effect level:
- 119 210 mg/m³ air
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- body weight and weight gain
- clinical signs
- Remarks on result:
- other: No toxic effect were observed.
- Critical effects observed:
- not specified
- Conclusions:
- Since no compound related effects on rats are observed, the no observed effect concentration (NOEC) relating to repeated dose for the given test material 4-chloro-1-methylpiperidine is estimated to be 119210 mg/m3 via inhalation route of administration using QSAR Toolbox version 3.4.
- Executive summary:
Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, repeated inhalation toxicity was predicted for the test compound 4-Chloro-1-methylpiperidine. The study assumed the use rats in repeated dose toxicity study. No significant alterations were noted at the dose level of 119210 mg/m3. The predicted no observed effect concentration (NOAEC)f or 4-Chloro-1-methylpiperidine is considered to be 119210 mg/m3.
Reference
The
prediction was based on dataset comprised from the following
descriptors: "study NOEL"
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" or "f" or "g" )
and ("h"
and (
not "i")
)
)
and "j" )
and ("k"
and (
not "l")
)
)
and ("m"
and (
not "n")
)
)
and "o" )
and "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 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
Domain
logical expression index: "c"
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: "d"
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 v1.4
Domain
logical expression index: "e"
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: "f"
Referential
boundary: The
target chemical should be classified as Narcotic Amine by Acute aquatic
toxicity MOA by OASIS
Domain
logical expression index: "g"
Referential
boundary: The
target chemical should be classified as Aliphatic Amines by Aquatic
toxicity classification by ECOSAR
Domain
logical expression index: "h"
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: "i"
Referential
boundary: The
target chemical should be classified as Highly reactive (GSH) OR Highly
reactive (GSH) >> Allyl chlorides and 1-alkyl substituted Allyl bromides
(SN2) OR Moderately reactive (GSH) OR Moderately reactive (GSH) >>
alpha-chloro toluenes (SN2) by Protein binding potency
Domain
logical expression index: "j"
Referential
boundary: The
target chemical should be classified as No superfragment by
Superfragments ONLY
Domain
logical expression index: "k"
Referential
boundary: The
target chemical should be classified as Alkyl halide AND Overlapping
groups AND Piperidine AND Saturated heterocyclic amine AND Saturated
heterocyclic fragment by Organic Functional groups (nested)
Domain
logical expression index: "l"
Referential
boundary: The
target chemical should be classified as Alcohol OR Aliphatic Amine,
primary OR Aliphatic Amine, secondary by Organic Functional groups
(nested)
Domain
logical expression index: "m"
Referential
boundary: The
target chemical should be classified as Alkyl halide AND Overlapping
groups AND Piperidine AND Saturated heterocyclic amine AND Saturated
heterocyclic fragment by Organic Functional groups (nested)
Domain
logical expression index: "n"
Referential
boundary: The
target chemical should be classified as Aryl halide OR Benzyl OR
Cycloalkane by Organic Functional groups (nested)
Domain
logical expression index: "o"
Referential
boundary: The
target chemical should be classified as Not calculated by Hydrolysis
half-life (Ka, pH 7)(Hydrowin) ONLY
Domain
logical expression index: "p"
Referential
boundary: The
target chemical should be classified as Narcotic Amine by Acute aquatic
toxicity MOA by OASIS ONLY
Domain
logical expression index: "q"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= 1.51
Domain
logical expression index: "r"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 2.08
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEC
- 119 210 mg/m³
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Data is of K2 reliability and predicted by QSAR toolbox.
Repeated dose toxicity: inhalation - local effects
Link to relevant study records
- Endpoint:
- repeated dose toxicity: inhalation, other
- Type of information:
- (Q)SAR
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification
- Justification for type of information:
- Data is predicted by OECD QSAR Toolbox version 3.4. The supporting QMRF report has been attached
- Qualifier:
- according to guideline
- Guideline:
- other: as mentioned below
- Principles of method if other than guideline:
- Data is predicted by OECD QSAR Toolbox version 3.4.
- 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 - Species:
- rat
- Strain:
- not specified
- Sex:
- not specified
- Route of administration:
- inhalation
- Type of inhalation exposure:
- not specified
- Vehicle:
- not specified
- Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- not specified
- Frequency of treatment:
- not specified
- Remarks:
- no data
- Control animals:
- not specified
- Details on study design:
- not specified
- Positive control:
- not specified
- Observations and examinations performed and frequency:
- not specified
- Sacrifice and pathology:
- not specified
- Other examinations:
- not specified
- Statistics:
- not specified
- Clinical signs:
- no effects observed
- Mortality:
- not specified
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not specified
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Key result
- Dose descriptor:
- NOEC
- Effect level:
- 119 210 mg/m³ air
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- body weight and weight gain
- clinical signs
- Remarks on result:
- other: No toxic effect were observed.
- Critical effects observed:
- not specified
- Conclusions:
- Since no compound related effects on rats are observed, the no observed effect concentration (NOEC) relating to repeated dose for the given test material 4-chloro-1-methylpiperidine is estimated to be 119210 mg/m3 via inhalation route of administration using QSAR Toolbox version 3.4.
- Executive summary:
Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, repeated inhalation toxicity was predicted for the test compound 4-Chloro-1-methylpiperidine. The study assumed the use rats in repeated dose toxicity study. No significant alterations were noted at the dose level of 119210 mg/m3. The predicted no observed effect concentration (NOAEC)f or 4-Chloro-1-methylpiperidine is considered to be 119210 mg/m3.
Reference
The
prediction was based on dataset comprised from the following
descriptors: "study NOEL"
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" or "f" or "g" )
and ("h"
and (
not "i")
)
)
and "j" )
and ("k"
and (
not "l")
)
)
and ("m"
and (
not "n")
)
)
and "o" )
and "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 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
Domain
logical expression index: "c"
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: "d"
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 v1.4
Domain
logical expression index: "e"
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: "f"
Referential
boundary: The
target chemical should be classified as Narcotic Amine by Acute aquatic
toxicity MOA by OASIS
Domain
logical expression index: "g"
Referential
boundary: The
target chemical should be classified as Aliphatic Amines by Aquatic
toxicity classification by ECOSAR
Domain
logical expression index: "h"
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: "i"
Referential
boundary: The
target chemical should be classified as Highly reactive (GSH) OR Highly
reactive (GSH) >> Allyl chlorides and 1-alkyl substituted Allyl bromides
(SN2) OR Moderately reactive (GSH) OR Moderately reactive (GSH) >>
alpha-chloro toluenes (SN2) by Protein binding potency
Domain
logical expression index: "j"
Referential
boundary: The
target chemical should be classified as No superfragment by
Superfragments ONLY
Domain
logical expression index: "k"
Referential
boundary: The
target chemical should be classified as Alkyl halide AND Overlapping
groups AND Piperidine AND Saturated heterocyclic amine AND Saturated
heterocyclic fragment by Organic Functional groups (nested)
Domain
logical expression index: "l"
Referential
boundary: The
target chemical should be classified as Alcohol OR Aliphatic Amine,
primary OR Aliphatic Amine, secondary by Organic Functional groups
(nested)
Domain
logical expression index: "m"
Referential
boundary: The
target chemical should be classified as Alkyl halide AND Overlapping
groups AND Piperidine AND Saturated heterocyclic amine AND Saturated
heterocyclic fragment by Organic Functional groups (nested)
Domain
logical expression index: "n"
Referential
boundary: The
target chemical should be classified as Aryl halide OR Benzyl OR
Cycloalkane by Organic Functional groups (nested)
Domain
logical expression index: "o"
Referential
boundary: The
target chemical should be classified as Not calculated by Hydrolysis
half-life (Ka, pH 7)(Hydrowin) ONLY
Domain
logical expression index: "p"
Referential
boundary: The
target chemical should be classified as Narcotic Amine by Acute aquatic
toxicity MOA by OASIS ONLY
Domain
logical expression index: "q"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= 1.51
Domain
logical expression index: "r"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 2.08
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Prediction model based estimation for target and data available for the structurally related chemicals was reviewed to determine the toxic nature of 4-Chloro-1-methylpiperidine (5570-77-4) upon repeated exposure by oral, dermal and inhalation route of exposure. The studies are as mentioned below as weight of evidence approach:
Repeated dose oral toxicity:
Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, repeated dose oral toxicity was predicted for the test compound 4-Chloro-1-methylpiperidine . The study assumed the use rats in repeated dose toxicity study. No significant alterations were noted at the dose level of 557.61 mg/kg/day. The predicted No Observed Adverse Effect Level (NOAEL) for 4-Chloro-1-methylpiperidine is considered to be 557.61 mg/kg/day.
Another combined repeated dose and reproduction / developmental screening was performed by Ministry of Health, Labour and Welfare", "Ministry of the Environment" and "National Institute of Technology and Evaluation (Jcheck, 2017) to determine the oral toxic nature 1-methylpiperazine(109-01-3). Combined Repeated Dose Toxicity Study with the Reproduction/ Developmental Toxicity Screening Test (OECD TG422) was performed to evaluate the toxic nature of the test compound1-Methylpiperazineupon repeated dosing by oral route. The test was performed onmale and femaleCrl:CD (SD) rats at dose levels of 0, 80, 200, 500 mg/kg/day. The animals were observed for clinical signs, body weight, food consumption, urinalysis, hematological and blood biochemistry parameters, gross and histopathological changes.
Repeated inhalation study:
Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, repeated inhalation toxicity was predicted for the test compound 4-Chloro-1-methylpiperidine. The study assumed the use rats in repeated dose toxicity study. No significant alterations were noted at the dose level of 119210 mg/m3. The predicted no observed effect concentration (NOEC) for 4-Chloro-1-methylpiperidine is considered to be 119210 mg/m3.
Another Repeated inhalation study for N,N-diethylethanamine ;other name : Triethylamin(121-44-8) was performed by NTRL (NTRL ,source; OTS0515254, 1987) to determine toxic nature of Triethylamin. The read across substances share high similarity in structure and log kow .Therefore, it is acceptable to derive information on mutation from the analogue substance. A repeated inhalation study for Triethylamin was conducted inmale and female F-344 rats. They were exposed at 0, 25, or 247 ppm triethylamine (TEA) vapor, 6 hr per day, 5 days per week for up to 28 weeks in order to characterize the subchronic organ system toxicity. Rats were weighed biweekly and scheduled sacrifices were performed following about 30, 60, and 120 days of exposure. No statistically significant treatment-related effects on organ weights, hematology, clinical chemistry, or electrocardiographic indices were observed. Body weight gain was not affected by TEA treatment. No physiologic or pathologic evidence of cardiotoxicity was seen in rats exposed to either TEA concencentrations for up to 28 weeks. No gross or histopathological lesions attributable to TEA exposure were noted in any of the organs examined, including the nasal passages.Based on the study results 25 ppm (corresponds to 103.3 mg/m³) is considered to be a NOAEC for Triethylamin . Hence the substance cannot be classified as toxicant.
Repeated dermal study
The acute toxicity value for 4-chloro-1-methylpiperidine (as provided in section 7.2.3) is >2000 mg/kg body weight. Also, given the use of the chemical; repeated exposure by the dermal route is unlikely since the use of gloves is common practice in industries. Thus, it is expected that 4-chloro-1-methylpiperidine shall not exhibit 28 day repeated dose toxicity by the dermal route. In addition, there is no data available that suggests that 4-chloro-1-methylpiperidine shall exhibit repeated dose toxicity by the dermal route. Hence this end point was considered for waiver.
Based on the data available for the target chemical, 4-Chloro-1-methylpiperidine (5570-77-4) and its structurally related substances and by applying weight of evidence approach, it can be considered that it does not exhibit toxic nature upon repeated exposure by oral, inhalation and dermal route of exposure and hence is not likely to classify as per the criteria mentioned in CLP regulation.
Justification for classification or non-classification
Based on the data available for the target chemical and its prediction, 4-Chloro-1-methylpiperidine (5570-77-4) does not exhibit toxic nature upon repeated exposure by oral, inhalation and dermal route of exposure and hence is not likely to classify as per the criteria mentioned in CLP regulation.
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