4-chloro-N-methylpiperidine

Short-term toxicity to fish

Link to relevant study record(s)

Reference

Endpoint:

short-term toxicity to fish

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

The supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

OECD Guideline 203 (Fish, Acute Toxicity Test)

Principles of method if other than guideline:

The data is predicted using the OECD QSAR toolbox version 3.3 with logKow as the primary descriptor.

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

Analytical monitoring:

not specified

Vehicle:

not specified

Test organisms (species):

Danio rerio (previous name: Brachydanio rerio)

Test type:

static

Water media type:

freshwater

Total exposure duration:

96 h

Test temperature:

21 Deg.C

pH:

8.1

Reference substance (positive control):

not specified

Key result

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

243.66 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Sublethal observations / clinical signs:

The prediction was based on dataset comprised from the following descriptors: LC50
Estimation method: Takes average value from the 7 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and "g" )  and ("h" and ( not "i") )  )  and ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and "n" )  and "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 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN2 OR SN2 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Aliphatic halides by DNA binding by OECD ONLY

Domain logical expression index: "c"

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

Domain logical expression index: "d"

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

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Carbamoylation after isocyanate formation OR AN2 >> Carbamoylation after isocyanate formation >> N-Hydroxylamines OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation >> Geminal Polyhaloalkane Derivatives OR AN2 >> Shiff base formation for aldehydes OR AN2 >> Shiff base formation for aldehydes >> Geminal Polyhaloalkane 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 >> 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) >> N-Hydroxylamines OR SN1 OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> N-Hydroxylamines OR SN2 OR SN2 >> Acylation involving a leaving group  OR SN2 >> Acylation involving a leaving group  >> Geminal Polyhaloalkane Derivatives OR SN2 >> Acylation involving a leaving group after metabolic activation OR SN2 >> Acylation involving a leaving group after metabolic activation >> Geminal Polyhaloalkane Derivatives OR SN2 >> 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 after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives by DNA binding by OASIS v.1.3

Domain logical expression index: "g"

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

Domain logical expression index: "h"

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

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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: "k"

Referential boundary: The target chemical should be classified as Di-substituted hydrocarbons (24a) OR Known precedent reproductive and developmental toxic potential OR Piperazine-, dioxane-, morpholine-, tetrahydrothiopyran-like derivatives and cyclohexanamine (17c) by DART scheme v.1.0

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as No alert found by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as H-acceptor-path3-H-acceptor by in vivo mutagenicity (Micronucleus) alerts by ISS

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"

Similarity boundary:Target: CN1CCC(Cl)CC1
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "p"

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

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.172

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.31

Validity criteria fulfilled:

not specified

Conclusions:

The median lethal concentration (LC50) value for 4-chloro-1-methylpiperidine on Danio rerio in a 96 hours study was estimated to be 243.66 mg/L on the basis of effects on mortality.

Executive summary:

Using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity on fish was predicted for target substance 4-chloro-1-methylpiperidine (CAS no. 5570-77-4). LC50 value was estimated to be 243.66 mg/l for Danio rerio for 96 hrs. duration. Based on this value it can be concluded that the substance 4-chloro-1-methylpiperidine is considered to be non-toxic to fish at environmentally relevant concentrations and can be considered to be not-classified as per the CLP classification criteria.

Description of key information

Using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity on fish was predicted for target substance 4-chloro-1-methylpiperidine (CAS no. 5570-77-4). LC50 value was estimated to be 243.66 mg/l for Danio rerio for 96 hrs. duration. Based on this value it can be concluded that the substance 4-chloro-1-methylpiperidine is considered to be non-toxic to fish at environmentally relevant concentrations and can be considered to be not-classified as per the CLP classification criteria.

Key value for chemical safety assessment

Fresh water fish

Fresh water fish

Effect concentration:

243.66 mg/L

Additional information

Five studies from prediction reports and experimental study from peer reviewed journal and authorative database for short term fish toxicity endpoint for test chemical 4-chloro-1-methylpiperidine (Cas no. 5570-77-4) with relevant read across which is close to target using Log Kow as descriptor were reviewed as follows:

 

Using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity to fish was predicted for 4-chloro-1-methylpiperidine (Cas no. 5570-77-4). LC50 value was estimated to be 243.66 mg/L on Danio rerio (previous name: Brachydanio rerio) for 96 hrs duration.

In another prediction done using the EPI Suite ECOSAR version 1.10 the 96 hours LC50 was estimated to be 261.626 mg/l on Fish for substance 4-chloro-1-methylpiperidine (Cas no. 5570-77-4) on the basis of mortality effects.

And Danish QSAR study indicate 96 hrs LC50 value of test substance 4-chloro-1-methylpiperidine on Fathead minnow was estimated by three different models i.e, Battery, Leadscope and SciQSAR used within Danish QSAR database. Based on mortality, the 96 hrs LC50 value was predicted to be 133.89 mg/l.

Above all predictions assist by experimental study for read across chemical Isopropyl amine (Cas no. 75-31-0) from peer reviewed journal The journal of toxicological science 7(3): 193-203;1982 which suggest The acute toxicity of nitrogen compounds including chemical Isopropyl amine was investigated in order to observed toxicity effects of chemicals on fish species  Oryzias latipes (Japanese Medaka). During experiment chemical dissolved in distilled water or n-octanol at the concentration of 100 mg/liter.And vehicle selected as Ethanol at concentration 1ml as needed. Test performed in static freshwater on test species Oryzias latipes at 25 deg.C temp.10 fish per vessels was used. And Determination of dissolved oxygen checked periodically with the help of Electrode sensor. In experiment measured concentration of 1000 mg/l was taken. After 48 hrs exposure period the median lethal concentration (LC50) was observed to be 1000 mg/l.

One another read across chemical Diisopropylamine (Cas no. 108-18-9) from authorative database suggest in Acute fish toxicity study, the lethal concentration (LC50) was determined for test substance Diisopropylamine with an exposure period of 96 hrs. on the basis of effects on mortality. Test organism was used as Danio rerio (Zebra Danio) in static freshwater system. Test condition maintained as 209.43 mg/L CaCO3 hardness; 23 deg.C test temp.pH 8.2 and dissolved oxygen >6.5 mg/L.From experiment the Lethal concentration to 50% of test organisms(LC50) on the basis of Mortality effect was observed to be 680 mg/l for exposure period of 96 hrs.(Ecotox database;2017)

All the above studies for target and read across substance indicate that the chemical is likely to be non toxic to fish with lethal concentration range 133.89-1000 mg/l. Thus, based on the available information, the test substance 4-chloro-1-methylpiperidine (Cas no. 5570-77-4) can be considered as non toxic to aquatic environment and thus not classified in aquatic environment as per the CLP criteria.