4-chloro-N-methylpiperidine

Endpoint summary

Description of key information

Skin irritation:

The dermal irritation potential of 4-chloro-1-methylpiperidine (CAS No: 5570-77-4) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The substance 4-chloro-1-methylpiperidine (CAS No: 5570-77-4) is estimated to be severely irritating to the skin of rabbits. Based on the estimated result N 4-chloro-1-methylpiperidine (CAS No: 5570-77-4) can be considered as severely irritating to skin and can be classified under the category “Category 1 (corrosive)” as per CLP regulation.

Eye irritation:

The ocular irritation potential of 4-chloro-1-methylpiperidine (CAS No: 5570-77-4) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The substance 4-chloro-1-methylpiperidine (CAS No: 5570-77-4) is estimated to be severely irritating to the eye of rabbits. Based on the estimated result N 4-chloro-1-methylpiperidine (CAS No: 5570-77-4) can be considered as severely irritating to eye and can be classified under the category “Category 2” as per CLP regulation.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Justification for type of information:

Data is from OECD QSAR toolbox version 3.3 and QMRF report has been attached.

Qualifier:

equivalent or similar to guideline

Guideline:

other: Estimated data

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Specific details on test material used for the study:

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

Species:

rabbit

Strain:

not specified

Details on test animals or test system and environmental conditions:

No data available

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

No data available

Duration of treatment / exposure:

8 days

Observation period:

8 days

Number of animals:

No data available

Details on study design:

No data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 8 d

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

skin irritating effects were observed.

Estimation method: Takes mode value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and "g" )  and "h" )  and ("i" and ( not "j") )  )  and "k" )  and ("l" and ( not "m") )  )  and ("n" and "o" )  )

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 Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "f"

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

Domain logical expression index: "g"

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

Domain logical expression index: "h"

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

Domain logical expression index: "i"

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: "j"

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

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 Alkyl chloride AND Alkyl halide AND Amine AND Halogen derivative AND Heterocyclic compound AND Tertiary aliphatic amine AND Tertiary amine by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Aromatic compound OR Aryl chloride OR Aryl halide OR Primary aliphatic amine OR Primary amine OR Secondary aliphatic amine OR Secondary amine by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.382

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.89

Interpretation of results:

Category 1 (corrosive) based on GHS criteria

Conclusions:

The substance 4-chloro-1-methylpiperidine (CAS No: 5570-77-4) is estimated to be severely irritating to the skin of rabbits. Based on the estimated result N 4-chloro-1-methylpiperidine (CAS No: 5570-77-4) can be considered as severely irritating to skin and can be classified under the category “Category 1 (corrosive)” as per CLP regulation.

Executive summary:

The dermal irritation potential of 4-chloro-1-methylpiperidine (CAS No: 5570-77-4) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The substance 4-chloro-1-methylpiperidine (CAS No: 5570-77-4) is estimated to be severely irritating to the skin of rabbits. Based on the estimated result N 4-chloro-1-methylpiperidine (CAS No: 5570-77-4) can be considered as severely irritating to skin and can be classified under the category “Category 1 (corrosive)” as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Justification for type of information:

Data is from OECD QSAR toolbox version 3.3 and QMRF report has been attached.

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Specific details on test material used for the study:

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

Species:

rabbit

Strain:

not specified

Details on test animals or tissues and environmental conditions:

No data available

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

No data available

Duration of treatment / exposure:

No data available

Observation period (in vivo):

No data available

Duration of post- treatment incubation (in vitro):

No data available

Number of animals or in vitro replicates:

No data available

Details on study design:

No data available

Irritation parameter:

overall irritation score

Basis:

mean

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

Eye irritating effects were observed in treated animals.

Estimation method: Takes mode value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Aliphatic Amines by US-EPA New Chemical Categories

Domain logical expression index: "b"

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

Domain logical expression index: "c"

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: "d"

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: "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 after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR AN2 >> Shiff base formation for aldehydes OR AN2 >> Shiff base formation for aldehydes >> Geminal Polyhaloalkane Derivatives OR AN2 >> Shiff base formation for aldehydes >> Haloalkane Derivatives with Labile Halogen OR Radical OR Radical >> Generation of reactive oxygen species OR Radical >> Generation of reactive oxygen species >> Thiols OR Radical >> Generation of ROS by glutathione depletion (indirect) OR Radical >> Generation of ROS by glutathione depletion (indirect) >> Haloalkanes Containing Heteroatom OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Haloalcohols OR Radical >> Radical mechanism via ROS formation (indirect) >> N-Hydroxylamines OR SN1 OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> N-Hydroxylamines OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Acylation involving a leaving group  OR SN2 >> Acylation involving a leaving group  >> Geminal Polyhaloalkane Derivatives OR SN2 >> Acylation involving a leaving group  >> Haloalkane Derivatives with Labile Halogen OR SN2 >> Acylation involving a leaving group after metabolic activation OR SN2 >> Acylation involving a leaving group after metabolic activation >> Geminal Polyhaloalkane Derivatives OR SN2 >> Alkylation by epoxide metabolically formed after E2 reaction OR SN2 >> Alkylation by epoxide metabolically formed after E2 reaction >> Haloalcohols OR SN2 >> Alkylation by epoxide metabolically formed after E2 reaction >> Monohaloalkanes OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Alkylation, direct acting epoxides and related after cyclization OR SN2 >> Alkylation, direct acting epoxides and related after cyclization >> Nitrogen Mustards OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkane Derivatives with Labile Halogen OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Monohaloalkanes OR SN2 >> Direct acylation involving a leaving group OR SN2 >> Direct acylation involving a leaving group >> Acyl Halides OR SN2 >> DNA alkylation OR SN2 >> DNA alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> DNA alkylation >> Vicinal Dihaloalkanes OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) >> Vicinal Dihaloalkanes OR SN2 >> Nucleophilic substitution after carbenium ion formation OR SN2 >> Nucleophilic substitution after carbenium ion formation >> Monohaloalkanes OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers by DNA binding by OASIS v.1.3

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as 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: "h"

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 of Heterocyclic Ring Systems 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 >> Alkyl phenols 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 OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Primary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN2 >> P450 Mediated Epoxidation OR SN2 >> P450 Mediated Epoxidation >> Thiophenes-SN2 by DNA binding by OECD

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Alkali Earth OR Alkaline Earth OR Metalloids OR Transition Metals by Groups of elements

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 17 - Halogens Cl AND Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Group 15 - Phosphorus P OR Group 16 - Oxygen O OR Group 16 - Sulfur S OR Group 17 - Halogens Br by Chemical elements

Domain logical expression index: "n"

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 Chlorine, aliphatic attach [-Cl] by Organic functional groups (US EPA)

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Acetylenic Carbon [#C] OR Amino, aliphatic attach [-NH-] OR Amino, aliphatic attach [-NH2] OR Amino-ethylcyano [-N-CH-C#N]  OR Aromatic Carbon [C] OR Chlorine, aromatic attach [-Cl] OR Chlorine, olefinic attach [-Cl] OR Cyano, aliphatic attach [-C#N] OR Olefinic carbon [=CH- or =C<] OR Tertiary Carbon by Organic functional groups (US EPA)

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Alkyl chloride AND Alkyl halide AND Amine AND Halogen derivative AND Heterocyclic compound AND Tertiary aliphatic amine AND Tertiary amine by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Aminal by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "r"

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

Domain logical expression index: "s"

Similarity boundary:Target: CN1CCC(Cl)CC1
Threshold=60%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.949

Domain logical expression index: "u"

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

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

The substance 4-chloro-1-methylpiperidine (CAS No: 5570-77-4) is estimated to be severely irritating to the eye of rabbits. Based on the estimated result N 4-chloro-1-methylpiperidine (CAS No: 5570-77-4) can be considered as severely irritating to eye and can be classified under the category “Category 2” as per CLP regulation.

Executive summary:

The ocular irritation potential of 4-chloro-1-methylpiperidine (CAS No: 5570-77-4) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The substance 4-chloro-1-methylpiperidine (CAS No: 5570-77-4) is estimated to be severely irritating to the eye of rabbits. Based on the estimated result N 4-chloro-1-methylpiperidine (CAS No: 5570-77-4) can be considered as severely irritating to eye and can be classified under the category “Category 2” as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

Various studieshas been investigated for the test chemical4-chloro-1-methylpiperidine (CAS No: 5570-77-4)to observe the potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits for target chemical4-chloro-1-methylpiperidine (CAS No: 5570-77-4) and its structurally similar read across substances1-methylpiperazine (CAS No: 109-01-3)and1-ethenylpyrrolidin-2-one (CAS No: 88-12-0).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

 

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the skin irritation potential was estimated for test chemical4-chloro-1-methylpiperidine (CAS No: 5570-77-4).The chemical 4-chloro-1-methylpiperidine (CAS No: 5570-77-4) is estimated to be severely irritating to skin of rabbits.

 

The above result was supported by experimental study conducted by Henry F. Smyth Jr., Charles P. Carpenter, Carrol S. Well, Urbano C. Pozzani & Jean A. Striegel (1962)on five rabbits’ belly to assess the degree of skin irritation of structurally similar read across substance 1-methylpiperazine (CAS No: 109-01-3). Each rabbits received 0.1mlof undiluted1-methylpiperazineor of solutions in water, propylene glycol, or acetoneon clipped belly skin for 24 hour under uncovered condition.Primary skin irritation on rabbits was recorded in a 10-grade ordinal series and was based upon the severest reaction that developed on the clipped skin of each of five albino rabbits. Grade 1 in indicated no irritation and Grade 2 the least visible capillary injection from the undiluted chemical. Grade 6 indicates necrosis when undiluted and Grade 10 indicates necrosis from a 0.01% solution.The primary skin Irritation score for1-methylpiperazine (CAS No: 109-01-3)was observed to be Grade 6 indicatingNecrosis of skin in treated rabbits. Thusbased on the grade, 1-methylpiperazine (CAS No: 109-01-3)was considered to be irritating to the skin of albino rabbits.

 

 

EUROPEAN COMMISSION JOINT RESEARCH CENTRE(2003) reported the skin irritation study of another structurally related read across substance 1-ethenylpyrrolidin-2-one (CAS No: 88-12-0) carried out to the ear of 3 rabbits in an early dermal toxicity study which further supports the above results. In this test, cotton wool plugs soaked in 1-ethenylpyrrolidin-2-one were bound to the ear of 3 rabbitsand were observed for skin reactions after exposure period of 4 , 8 or 16 hours.Transient swellings, which bled profusely, were reported for the rabbit exposed for 4 hours. Exposures of 8 or 16 hours led to swelling and blistering. The animal exposed for 16 hours subsequently died. Skin lesions in the animal exposed for 8 hours formed crusts with egg white-like secretions, which healed after 6 week leaving scarring.Since the chemical induce sever cutaneous reactions, the chemical1-ethenylpyrrolidin-2-one (CAS No: 88-12-0) was considered to be severely irritating to the skin.

 

 

Based on the available data for thetarget chemical4-chloro-1-methylpiperidine (CAS No: 5570-77-4) and its structurally similar read across substances1-methylpiperazine (CAS No: 109-01-3)and1-ethenylpyrrolidin-2-one (CAS No: 88-12-0),it can be concluded thatchemical 4-chloro-1-methylpiperidine (CAS No: 5570-77-4) is able to cause severe skin irritation and hence considered as corrosive .Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category“Category 1 (corrosive)”.

 

 

Eye irritation:

In different studies,the test chemical4-chloro-1-methylpiperidine (CAS No: 5570-77-4) has been investigated for potential for ocular irritationto a greater or lesser extent. The studies are based on in vivo experiments in rabbits for target chemical4-chloro-1-methylpiperidine (CAS No: 5570-77-4) and its structurally similar read across substances1-methylpiperazine (CAS No: 109-01-3)and1-ethenylpyrrolidin-2-one (CAS No: 88-12-0).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

 

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, an eye irritation potential was estimated for test chemical4-chloro-1-methylpiperidine (CAS No: 5570-77-4).The chemical 4-chloro-1-methylpiperidine (CAS No: 5570-77-4) is estimated to be severely irritating to eye of rabbits.

 

The above result was supported by experimental study conducted by Henry F. Smyth Jr., Charles P. Carpenter, Carrol S. Well, Urbano C. Pozzani & Jean A. Striegel (1962) forstructurally similar read across substance1-methylpiperazine (CAS No: 109-01-3) in rabbits.In this test,eye injury in rabbits was recorded in a 10- grade ordinal series and was based upon the degree of corneal necrosis that results from instillation of various volumes and concentrations of chemical1-methyl piperazine. Grade 1 indicated at most a very small area of necrosis resulting from 0.5 ml of undiluted chemical in the eye. Grade 5 indicated a so-called severe burn from 0.005 ml, and Grade 10 indicated a severe burn from 0.5 ml of a 1% solution in water or propylene glycol.Primary Eye Irritation score for1-methyl piperazinewas observed to be Grade 8. Thusbased on the grade, 1-methylpiperazine (CAS No: 109-01-3)was considered to be severely irritating to eyes.

 

 

EUROPEAN COMMISSION JOINT RESEARCH CENTRE(2003) reported the The Draize test of another structurally related read across substance 1-ethenylpyrrolidin-2-one (CAS No: 88-12-0) in six New Zealand white rabbits to determine its eye irritancy potential. About 0.1ml of 1-ethenylpyrrolidin-2-one was installed into the eye of each rabbit and observations were made according to the EU classification and labeling system for scoring eye irritation after 1, 24, 48, 72 hours and 7 days. One hour after application, grade 1redness and grade 1 or 2 chemosis of the conjunctiva and grade 1 iris lesions were recorded for all animals. In addition, one animal showed grade 1 corneal opacity. The conjunctival chemosis grade 2.2, conjunctival redness grade 1.9 and grade 1 iris lesions were observed across the 24-72 hour time points. In addition, corneal opacities of grade 1.8 were observed, which extended over an area of three quarters to the entire cornea. The lesions of the iris and conjunctiva did not show any signs of diminishing up to day 7 and corneal opacities became worse. By day 7, grade 2 (1 rabbit) or grade 3 (5 rabbits) opacities were observed covering an area of half to the entire cornea. Discharge, grade 1 or 2, was also apparent from the eyes of all rabbits at all observation points. Since the ocular lesions were not cleared and becoming more severe with time, the chemical1-ethenylpyrrolidin-2-one (CAS No: 88-12-0) was considered to be severely irritating to the eye of New Zealand white rabbits.

 

 

Based on the available data for thetarget chemical4-chloro-1-methylpiperidine (CAS No: 5570-77-4) and its structurally similar read across substances1-methylpiperazine (CAS No: 109-01-3)and1-ethenylpyrrolidin-2-one (CAS No: 88-12-0),it can be concluded thatchemical 4-chloro-1-methylpiperidine (CAS No: 5570-77-4) is able to cause severe eye irritation and hence considered as irritating.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category“Category 2”.

Justification for classification or non-classification

The skin and eye irritation potential of test chemical4-chloro-1-methylpiperidine (CAS No: 5570-77-4) and its structurally similar read across substances1-methylpiperazine (CAS No: 109-01-3)and1-ethenylpyrrolidin-2-one (CAS No: 88-12-0)were observed in various studies. The results obtained from these studies indicates that the chemical4-chloro-1-methylpiperidine (CAS No: 5570-77-4)is likely to cause severe skin and eye irritation. Hence4-chloro-1-methylpiperidine (CAS No: 5570-77-4)can be classified under the category“Category 1 (corrosive)”for skin and“Category 2”eye as per CLP.