4-chloro-N-methylpiperidine

Endpoint summary

Description of key information

Short-term toxicity to fish

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.

Short-term toxicity to aquatic invertebrates

The median effective concentration (EC50) for the test substance,4-chloro-1-methylpiperidine, in Daphnia magna was determined to be 206.1mg/L on the basis of mobiity inhibition effects in a 48 hour study.

Toxicity to aquatic algae and cyanobacteria

The median effective concentration (EC50) for the test substance, 4-chloro-1-methylpiperidine, in Desmodesmus subspicatus was determined to be 77.2 mg/L on the basis of effects on growth rate in a 72 hour study.

Toxicity to microorganisms

The toxicity to micro organism of the substance 4-chloro-1-methylpiperidine (Cas no. 5570-77-4) to micro organism Tetrahymena pyriformis is predicted using QSAR toolbox version.3.3, based on the effects observed in a static freshwater system during a 48 hr exposure. The Inhibition growth concentration (IGC50) for the substance 4-chloro-1-methylpiperidine is estimated to be 240.91 mg/L.

Additional information

Short-term toxicity to fish

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.

Short-term toxicity to aquatic invertebrates

The experimental key study of target substance 4-chloro-1-methylpiperidine (CAS no. 5570-77-4) and supporting studies including predicted data from validated tools for target and experimental data from authoritative database for structurally similar substance which is close to target are summarised for short term aquatic invertebrate’s endpoint as follows:

In a key study done by SSS, determination of the inhibition of the mobility of daphnids was carried out with the substance 4-chloro-1-methylpiperidine according to OECD Guideline 202. The test substance was tested at the concentrations 5, 10, 20, 40, 80 and 160 mg/L. Effects on immobilisation were observed for 48 hours. The median effective concentration (EC50) for the test substance, 4-chloro-1-methylpiperidine, in Daphnia magna was determined to be 206.1 mg/L for immobilisation effects. This value indicates that the substance is likely to be non-hazardous to aquatic invertebrates and can be considered as Not classified as per the CLP criteria.

Using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the six closest read across substances, which indicate the short term toxicity on aquatic invertebrates was predicted for 4-chloro-1-methylpiperidine(CAS no. 5570-77-4) and the Effect concentration i.e EC50 value was estimated to be 168.51 mg/l for Daphnia magna for 48 hrs duration.

Similarly prediction by EPI suite, ECOSAR version 1.1, on the basis of similarity of structure to chemicals for which the aquatic toxicity has been previously measured by structure-activity relationships (SARs) program suggest the LC50 value for short term toxicity to aquatic invertebrates was predicted. On the basis of EPI suite, ECOSAR version 1.1, the LC50 value for short term toxicity to aquatic invertebrates was predicted to be 142.902 mg/l for 4-chloro-1-methylpiperidine in 48 hrs.  

Above both predicted results of target assist by experimental result of read across chemical1-(5-tert-butyl-1,3,4-thiadiazol-2-yl)-1,3-dimethylurea (CAS no. 34014-18-1) authoritative database i.e ECOTOX database indicate Short term toxicity to aquatic invertebrates was performed in Daphnia magna (Water Flea) for 48 hrs with <10 h age. Test in fresh water media with static condition. During the experiment, the EC50 value for 1-(5-tert-butyl-1,3,4-thiadiazol-2-yl)-1,3-dimethylurea (Cas no. 34014 -18 -1)was determined to be 297 mg/l on the basis of mobility. 

Again from ECOTOX database for another read across 3-cyclohexyl-6-(dimethylamino)-1-methyl-1,2,3,4-tetrahydro-1,3,5-triazine-2,4-dione (Hexazinone) (CAS no. 51235-04-2) indicate Short term toxicity to aquatic invertebrates was performed in Daphnia magna (Water Flea) for 48 hrs with <24 d age. Test in fresh water media with static condition and test condition maintain as 22 deg. test temp.,7.4 pH and 8.6 mg/l dissolved oxygen. During the experiment, the LC50 value for 3-cyclohexyl-6-dimethylamino-1-methyl-1,2,3,4-tetrahydro-1,3,5-triazine-2,4-dione (Hexazinone) (CAS no. 51235 -04 -2)was determined to be 152 mg/l on the basis of mortality.

Same data source (ECOTOX database) for one another read across chemical Fats and Glyceridicoils, tobacco seed (CAS no. 8037-19-2) indicate Short term toxicity to aquatic invertebrates was performed in Daphnia magna (Water Flea) for 48 hrs with <24 h age. Test in fresh water media with static condition. During the experiment, the EC50 value for Fats and Glyceridicoils, tobacco seed (CAS no. 8037-19-2) was determined to be 169 mg/l on the basis of mobility.

Thus based on the value from experimental key study gives the conclusion that test substance 4-chloro-1-methylpiperidine (CAS No. 5570-77-4) is likely to be non toxic to aquatic invertebrates, hence it can be considered to be not classified as per the CLP regulation for short term toxicity to aquatic invertebrate.

Toxicity to aquatic algae and cyanobacteria

The experimental key study of target substance 4-chloro-1-methylpiperidine (CAS No. 5570-77-4) and supporting predicted study from validated tools are summarised for short term aquatic algae endpoint as follows:

In a key study conducted by SSS, Freshwater algal growth inhibition test was carried out on Desmodesmus subspicatus with the substance 4-chloro-1-methylpiperidine according to OECD Guideline 201. The test substance was dissolved in DMSO/ OECD growth medium and tested at the concentrations 10, 19, 35, 65 and 120 mg/L. Effects on the growth rate of the organism were studied. The median effective concentration (EC50) for the test substance, 4-chloro-1-methylpiperidine, in Desmodesmus subspicatus was determined to be 77.2 mg/L. This value indicates that the substance is likely to be hazardous to aquatic algae and can be classified as Aquatic chronic 3 as per the CLP criteria.

In supporting study the short-term toxicity of the test substance 4-chloro-1-methylpiperidine (CAS No. 5570-77-4) to green algae is predicted using EPI Suite ECOSAR version 1.11. On the basis of effects observed in a static freshwater system during a 96 hr exposure, the effect concentration (EC50) for the substance is estimated to be 90.678 mg/L. Based on this value, it can be concluded that the test chemical 4-chloro-1-methylpiperidine can be considered as toxic to green algae at environmentally relevant concentrations and can be considered to be classified in aquatic chronic category 3 as per the CLP classification criteria.

Thus based on the value from experimental key study gives the conclusion that test substance 4-chloro-1-methylpiperidine (CAS No. 5570-77-4) is likely to be toxic to aquatic algae and can be classified as Aquatic chronic category 3 as per the CLP regulation.

Toxicity to microorganisms

Predicted data for the target substance 4-chloro-1-methylpiperidine and experimental study for its structurally similar substance has been reviewed for toxicity to microorganism endpoint and are presented below as weight of evidence approach:

The toxicity to micro organism of the substance 4-chloro-1-methylpiperidine (Cas no. 5570-77-4) to micro organism Tetrahymena pyriformis is predicted using QSAR toolbox version.3.3, based on the effects observed in a static freshwater system during a 48 hr exposure. The Inhibition growth concentration (IGC50) for the substance 4-chloro-1-methylpiperidine is estimated to be 240.91 mg/L. Based on this value, it can be concluded that the test chemical 4-chloro-1-methylpiperidine (Cas no. 5570-77-4) may have no concern to micro organism toxicity for acute exposure period.

As per the data available in IUCLID dataset, 2000; Bacterial growth inhibition test of the structurally similar substance N-Methyldiethanolamine (CAS 105-59-9) was carried out as per DIN 38412/8 method. Pseudomonas putida was the bacteria used to measure the effects. The 50% effective concentration i.e. EC50 value of the substance N-Methyldiethanolamine based on growth inhibition to bacteria Pseudomonas putida was determined to be 410 mg/l after 17 hours of exposure.

Thus by applying weight of evidence approach it can be concluded that the substance 4-chloro-1-methylpiperidine is not that toxic to microorganisms.