4-chloro-N-methylpiperidine

Endpoint summary

Description of key information

Acute oral toxicity:

LD50 was estimated to be 3689 mg/kg bw when rats were orally exposed with 4-chloro-1-methylpiperidine.

Acute inhalation toxicity:

LC50 was estimated to be 27300 mg/m³when B6C3F1 male and female mice were inhaled by vapour using whole body for 4 hours.

Acute dermal toxicity:

LD50 was estimated to be 2018 mg/kg bw when New Zealand White male and female rabbits were treated with 4-chloro-1-methylpiperidine occlusive by dermal application.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 689 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from OECD QSAR toolbox

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

27 300 mg/m³ air

Quality of whole database:

Data is Klimisch 2 and from OECD QSAR toolbox

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 018 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from OECD QSAR toolbox

Additional information

Acute oral toxicity:

In different studies, 4-chloro-1-methylpiperidine has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimations in rodents, i.e. most commonly in rats for 4-chloro-1-methylpiperidinealong with the study available on structurally similar read across substance 2-Chlorobutane (CAS no 78-86-4) and Ethanol, 2.2’-(methylimino)bis- (CAS no 105-59-9). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 4-chloro-1-methylpiperidine. The LD50 was estimated to be 3689 mg/kg bw when rats were orally exposed with 4-chloro-1-methylpiperidine.

In another experimental study conducted by Smythet al (American Industrial Hygiene Association Journal, 30:5, 470-476, 1969) on structurally similar read across substance 2-Chlorobutane (CAS no 78-86-4), rat were treated with 2-Chlorobutane in the concentration of 17460 mg/kg bw orally. 50 % mortality observed in 17460 mg/kg bw treated rats. Therefore, LD50 was considered to be 17460 mg/kg bw (11174—27324) when rat were treated with 2-Chlorobutane orally. 

This is further supported by experimental study summarize by European Chemicals Bureau (IUCID Data set, European Chemicals Bureau, 18–FEB–2000, 58) on structurally similar read across substance Ethanol, 2.2’-(methylimino)bis- (CAS no 105-59-9), five Carworth –Wistar rats were treated with 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.

Further this is supported by another experimental study summarize by European Chemicals Bureau (IUCID Data set, European Chemicals Bureau, 18–FEB–2000, 58) on structurally similar read across substance Ethanol, 2.2’-(methylimino)bis- (CAS no 105-59-9),rats were treated with 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 the above studies and predictions on 4-chloro-1-methylpiperidine and its read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 4-chloro-1-methylpiperidine can be Not classified for acute oral toxicity.

Acute inhalation toxicity:

In different studies, 4-chloro-1-methylpiperidine has been investigated for acute inhalation toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimations in rodents, i.e. most commonly in mice and rats for 4-chloro-1-methylpiperidinealong with the study available on structurally similar read across substance 1-Methylpiperazine (CAS no: 109-01-3) and Chloromethane (CAS no: 74-87-3). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute inhalation toxicity was estimated for 4-chloro-1-methylpiperidine. The LC50 was estimated to be 27300 mg/m³when B6C3F1 male and female mice were inhaled by vapour using whole body for 4 hours.

In another experimental study summarized by U.S. National Library of Medicine (ChemIDplus, A Toxnet Database, 2017) on structurally similar read across substance 1-Methylpiperazine (CAS no: 109-01-3), mice were inhaled with 2-Chlorobutane in the concentration of 2740 mg/m³. 50 % mortality observed at 2740 mg/m3 and Behavioral Excitement, Dyspnea Lungs, Thorax or Respiration and Muscle Contraction or Spasticity was observed in exposed mice. Therefore, LC50 was considered to be 2740 mg/m³when mice were inhaled with 1-Methylpiperazine. 

This further supported by experimental study summarized by OECD SIDS (OECD SIDS, UNEP Publications, 19 March 2003) on structurally similar read across substance Chloromethane (CAS no: 74-87-3), mice were inhaled with Chloromethane in the concentration of 5300 mg/m3. 50 % mortality observed at 5300 mg/m3 in exposed rat. Therefore, LC50 was considered to be 5300 mg/m3 when rat were inhaled with Chloromethane for 4 hours.   

Thus, based on the above studies and predictions on 4-chloro-1-methylpiperidine and its read across substances and by applying weight of evidence, it can be concluded that LC50 value is greater than 20 mg/m3. Thus, comparing this value with the criteria of CLP regulation, 4-chloro-1-methylpiperidine can be Not classified for acute inhalation toxicity.

Acute dermal toxicity:

In different studies, 4-chloro-1-methylpiperidine has been investigated for acute dermal toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimations in rodents, i.e. most commonly in mice and rats for 4-chloro-1-methylpiperidine along with the study available on structurally similar read across substance 2-Chlorobutane (CAS no 78-86-4) and Bis(trimethoxysilylpropyl)amine (CAS no 82985-35-1).The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for 4-chloro-1-methylpiperidine. The LD50 was estimated to be 2018 mg/kg bw when New Zealand White male and female rabbits were treated with 4-chloro-1-methylpiperidine occlusive by dermal application.

In another experimental study conducted by Smythet al (American Industrial Hygiene Association Journal, 30:5, 470-476, 1969) on structurally similar read across substance 2-Chlorobutane (CAS no 78-86-4), rabbits were treated with 2-Chlorobutane in the concentration of 17460 mg/kg bw orally. 50 % mortality was observed at 17460 mg/kg bw in treated rabbits. Therefore, LD50 was considered to be 17460 mg/kg bw when rabbits were treated with 2-Chlorobutane by single dermal application.

This further supported by experimental study summarized by Union Carbide Corp (NTRL, National Technical Information Service. Vol. OTS0533892, 1992) on structurally similar read across substance Bis(trimethoxysilylpropyl)amine (CAS no 82985-35-1),rabbits were treated with Bis(trimethoxysilylpropyl)amine by occlusive covering for 6 hours. 50 % mortality observed in treated male at 16640 mg/kg bw and at 11752mg/kg bw in female rabbitsand Lungs, Thorax or Respiration Changes, Somnolence (General Depressed Activity) and Dermatitis were observed in treated rabbits. Therefore,LD50 was considered to be 16640 mg/kg bw for male and 11752mg/kg bw in female when male and female rabbits were treated with Bis(trimethoxysilylpropyl)amine by single dermal application for 6 hours.

Thus, based on the above studies and predictions on 4-chloro-1-methylpiperidine and its read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 4-chloro-1-methylpiperidine can be Not classified for acute dermal toxicity.

Justification for classification or non-classification

Based on the above studies and predictions on 4-chloro-1-methylpiperidine and its read across substances, it can be concluded that LD50 and LC50 value is greater than the classifing value . Thus, comparing this value with the criteria of CLP regulation, 4-chloro-1-methylpiperidine can be Not classified for acute oral, inhalation and dermal toxicity.