4-chloro-N-methylpiperidine

Endpoint summary

Description of key information

Hydrolysis

Hydrolysis of 4-chloro-1-methylpiperidine (CAS no. 5570 -77 -4) is predicted using OECD QSAR toolbox version 3.3 (2017) with logKow as the primary descriptor. The estimated half-life of 4-chloro-1-methylpiperidine was estimated to be 92.6 days, indicating that it is not hydrolysable.

Biodegradation in water

Biodegradability of 4-chloro-1-methylpiperidine (CAS no. 5570 -77 -4) is predicted using OECD QSAR toolbox version 3.3 (2017) with logKow as the primary descriptor. Test substance undergoes 0.166% degradation by BOD in 28 days. Thus, based on percentage degradation, the test chemical 4-chloro-1-methylpiperidine was estimated to be not readily biodegradable in water.

Biodegradation in water and sediment

Estimation Programs Interface (EPI Suite, 2017) prediction model was run to predict the half-life in water and sediment for the test compound 4-chloro-1-methylpiperidine (CAS No. 5570 -77 -4). If released in to the environment, 25.5% of the chemical will partition into water according to the Mackay fugacity model level III and the half-life period of 4-chloro-1-methylpiperidine in water is estimated to be 37.5 days (900 hrs). The half-life (37.5 days estimated by EPI suite) indicates that the chemical is not persistent in water and the exposure risk to aquatic animals is moderate to low whereas the half-life period of 4-chloro-1-methylpiperidine in sediment is estimated to be 337.5 days (8100 hrs). However, as the percentage release of test chemical into the sediment is less than 1% (i.e, reported as 0.154%), indicates that 4-chloro-1-methylpiperidine is not persistent in sediment.

Biodegradation in soil

The half-life period of 4-chloro-1-methylpiperidine (CAS No. 5570 -77 -4) in soil was estimated using Level III Fugacity Model by EPI Suite version 4.1 estimation database (EPI suite, 2017). If released into the environment, 74.2% of the chemical will partition into soil according to the Mackay fugacity model level III. The half-life period of 4-chloro-1-methylpiperidine in soil is estimated to be 75 days (1800 hrs). Based on this half-life value of 4 -chloro-1 -methylpiperidine, it is concluded that the chemical is not persistent in the soil environment and the exposure risk to soil dwelling animals is moderate to low.

Bioaccumulation: aquatic/sediment

BCFBAF model (v3.01) of Estimation Programs Interface (EPI Suite, 2017) prediction program was used to predict the bioconcentration factor (BCF) of test chemical 4 -chloro-1 -methylpiperidine (CAS No. 5570 -77 -4). The bioconcentration factor (BCF) of 4-chloro-1-methylpiperidine was estimated to be 5.123 L/kg whole body w.w (at 25 deg C) which does not exceed the bioconcentration threshold of 2000, indicating that the chemical 4-chloro-1-methylpiperidine is not expected to bioaccumulate in the food chain.

Adsorption/desorption

The adsorption coefficient Koc in soil and in sewage sludge 4-chloro-1-methylpiperidine (CAS No.5570 -77 -4) was determined by the Reverse Phase High Performance Liquid Chromatographic method according to OECD Guideline No. 121 for testing of Chemicals (Sustainability Support Services (Europe) AB, Report no. 5570-77-4/01/2017/Koc, 2017).The solutions of the test substance and reference substances were prepared in appropriate solvents. A test item solution was prepared by accurately measuring 4 μL of test item and diluted with acetonitrile up to 10 ml. Thus, the test solution concentration was 416 mg/l. The pH of test substance was 8.48. Each of the reference substance and test substance were analysed by HPLC at 210 nm. After equilibration of the HPLC system, Urea was injected first, the reference substances were injected in duplicate, followed by the test chemical solution in duplicate. Reference substances were injected again after test sample, no change in retention time of reference substances was observed. Retention time tR were measured, averaged and the decimal logarithms of the capacity factors k were calculated. The graph was plotted between log Koc versus log k(Annex - 2).The linear regression parameter of the relationship log Koc vs log k were also calculated from the data obtained with calibration samples and therewith, log Koc of the test substance was determined from its measured capacity factor. The reference substances were chosen according to estimated Koc range of the test substance and generalized calibration graph was prepared. The reference substances were having Koc value ranging from 1.25 to 4.09. The Log Koc value was determined to be 1.8537 ± 0.0093 at 25°C. This log Koc value indicates that the substance 4-chloro-1-methylpiperidine has a low sorption to soil and sediment and therefore have moderate migration potential to ground water.

Additional information

Hydrolysis

The predicted data for the target substance 4-chloro-1-methylpiperidine and the available data for its structurally similar substance were reviewed for hydrolysis endpoint and are presented as weight of evidence approach as follows:

Hydrolysis of 4-chloro-1-methylpiperidine (CAS no. 5570 -77 -4) is predicted using OECD QSAR toolbox version 3.3 (2017) with logKow as the primary descriptor. The estimated half-life of 4-chloro-1-methylpiperidine was estimated to be 92.6 days, indicating that it is not hydrolysable.

As part of a study in which the structurally similar substance 1-ethenylpyrrolidin-2-one (CAS 88 -12 -0) was administered in drinking water, 1-ethenylpyrrolidin-2-one was shown to be stable in drinking water for at least 4 days. Hence it can be considered that the test substance is slowly hydrolysable in water.

Considering above data it can be assumed that the target substance 4-chloro-1-methylpiperidine is slowly to negligibly hydrolysable and stable in water.

Biodegradation in water

Various predicted data for the target compound 4-chloro-1-methylpiperidine (CAS No. 5570-77-4) and supporting weight of evidence studies for its read across substance were reviewed for the biodegradation end point which are summarized as below:

 

In a prediction done by SSS (2017) using OECD QSAR toolbox version 3.3 with logKow as the primary descriptor, percentage biodegradability of test chemical, 4-chloro-1-methyl piperidine (CAS No. 5570-77-4) was estimated.Test substance undergoes 0.166% degradation by BOD in 28 days. Thus, based on percentage degradation, the test chemical 4-chloro-1-methylpiperidine was estimated to be not readily biodegradable in water.

 

In another prediction using the Estimation Programs Interface Suite (EPI suite, 2017), the biodegradation potential of the test compound 4-chloro-1-methylpiperidine (CAS No. 5570-77-4) in the presence of mixed populations of environmental microorganisms was estimated.The biodegradability of the substance was calculated using seven different models such as Linear Model, Non-Linear Model, Ultimate Biodegradation Timeframe, Primary Biodegradation Timeframe, MITI Linear Model, MITI Non-Linear Model and Anaerobic Model (called as Biowin 1-7, respectively) of the BIOWIN v4.10 software. The results indicate that chemical 4-chloro-1-methylpiperidine is expected to be not readily biodegradable.

 

In a supporting weight of evidence study from authoritative database (J-CHECK, 2017 and Envichem, 2014) for the read across chemicalsubstance 1-methylpiperidine (CAS no. 626-67-5), biodegradation experiment was conducted for 28 days for evaluating the percentage biodegradability of read across substance 1 -methylpiperidine. Concentration of inoculum i.e, sludge used was 30 mg/l and initial test substance conc. used in the study was 100 mg/l, respectively. The percentage degradation of substance 1 -methylpiperidine was determined to be 1 and 2% degradation by BOD, TOC removal and GC parameter in 28 days. Thus, based on percentage degradation,1 -methylpiperidine is considered to be not readily biodegradable in nature.

 

Another biodegradation study was conducted for 28 days for evaluating the percentage biodegradability of read across substance 2,2'-(methylimino)diethanol (CAS no. 105 -59 -9) (J-CHECK, 2017 and secondary source OECD SIDS, 2012). The study was performed according to OECD Guide-line 301 C "Ready Biodegradability: Modified MITI Test (I)". Concentration of inoculum i.e, sludge used was 30 mg/l and initial test substance conc. used in the study was 100 mg/l, respectively. The percentage degradation of substance 2,2'-(methylimino)diethanol was determined to be 7, 23 and 25% degradation by BOD, TOC removal and HPLC parameter in 28 days. Thus, based on percentage degradation, 2,2'-(methylimino)diethanol is considered to be not readily biodegradable in nature.

 

On the basis of above results for target chemical 4 -chloro-1 -methylpiperidine (from OECD QSAR toolbox version 3.3 and EPI suite, 2017) and for its read across substance (from authoritative database J-CHECK, Envichem and secondary source OECD SIDS), it can be concluded that the test substance 4 -chloro-1 -methylpiperidine can be expected to be not readily biodegradable in nature.

 

Biodegradation in water and sediment

Estimation Programs Interface (EPI Suite, 2017) prediction model was run to predict the half-life in water and sediment for the test compound 4-chloro-1-methylpiperidine (CAS No. 5570 -77 -4). If released in to the environment, 25.5% of the chemical will partition into water according to the Mackay fugacity model level III and the half-life period of 4-chloro-1-methylpiperidine in water is estimated to be 37.5 days (900 hrs). The half-life (37.5 days estimated by EPI suite) indicates that the chemical is not persistent in water and the exposure risk to aquatic animals is moderate to low whereas the half-life period of 4-chloro-1-methylpiperidine in sediment is estimated to be 337.5 days (8100 hrs). However, as the percentage release of test chemical into the sediment is less than 1% (i.e, reported as 0.154%), indicates that 4-chloro-1-methylpiperidine is not persistent in sediment.

Biodegradation in soil

The half-life period of 4-chloro-1-methylpiperidine (CAS No. 5570 -77 -4) in soil was estimated using Level III Fugacity Model by EPI Suite version 4.1 estimation database (EPI suite, 2017). If released into the environment, 74.2% of the chemical will partition into soil according to the Mackay fugacity model level III. The half-life period of 4-chloro-1-methylpiperidine

in soil is estimated to be 75 days (1800 hrs). Based on this half-life value of 4 -chloro-1 -methylpiperidine, it is concluded that the chemical is not persistent in the soil environment and the exposure risk to soil dwelling animals is moderate to low.

On the basis of available information, the test substance 4 -chloro-1 -methylpiperidine can be considered to be not readily biodegradable in nature.

Bioaccumulation: aquatic/sediment

Various predicted data for the target compound 4-chloro-1-methylpiperidine (CAS No. 5570-77-4) and the supporting weight of evidence studies for its read across substance were reviewed for the bioaccumulation end point which are summarized as below:

 

In a prediction done using theBCFBAF Model (v3.01) of Estimation Programs Interface (EPI Suite, 2017) the bioconcentration factor (BCF) of 4-chloro-1-methylpiperidine was estimated to be 5.123 L/kg whole body w.w (at 25 deg C).

 

In an another prediction done by using Bio-concentration Factor (v12.1.0.50374) module, the BCF value of the test substance 4-chloro-1-methylpiperidine (CAS no. 5570 -77 -4) at pH range 0-7, 8, 9, 10 and at range 11-14 was estimated to be approx. 1, 2.91, 4.78, 5.10 and 5.14 respectively.

 

Bioaccumulation test was conducted for estimating the bioconcentration factor (BCF) of test chemical 4-chloro-1-methylpiperidine (CAS no. 5570 -77 -4)(ChemSpider, 2017). The bioconcentration factor (BCF) of 4-chloro-1-methylpiperidine was estimated to be 1.00 and 1.93 at pH 5.5 and 7.4, respectively.

 

Another prediction was done using SciFinder database (American Chemical Society (ACS), 2017) for the bioconcentration factor (BCF) of test chemical 4-chloro-1-methylpiperidine (CAS No. 5570 -77 -4). The estimated bioconcentration factor (BCF) of 4-chloro-1-methylpiperidine was estimated to be 1 at pH range from 1-7 and 3.97, 6.50 and 6.95 at pH 8, 9 and 10, respectively (at 25 deg C).

 

From CompTox Chemistry Dashboard using OPERA (OPEn (quantitative) structure-activity Relationship Application) V1.02 model in which calculation based on PaDEL descriptors (calculate molecular descriptors and fingerprints of chemical), the bioaccumulation i.e BCF for test substance 4-chloro-1-methylpiperidine was estimated to be 12.2 dimensionless. The predicted BCF result based on the 5 OECD principles. Thus based on the result it is concluded that the test substance 4-chloro-1-methylpiperidine is non-bioaccumulative in nature.

 

In a supporting weight of evidence study from authoritative database (J-CHECK, 2017) for the read across chemical 1-methylpiperidine (CAS no. 626-67-5), bioaccumulation experiment was conducted on test organism Cyprinus carpio for 6 weeks for evaluating the bioconcentration factor (BCF value) of 1-methylpiperidine under static conditions. The study was performed according to other guideline "Bioaccumulation test of a chemical substance in fish or shellfish" provided in "the Notice on the Test Method Concerning New Chemical Substances". Cyprinus carpio was used as a test organism for the study. Details on analytical methods involve the recovery ratio: Test water : 1st concentration area : 98.4%, 2nd concentration area : 94.8 %, Fish : 93.3%, Limit of detection : Test water : 1stconcentration area: 0.04 ppm, 2ndconcentration area: 0.004 ppm, Fish: 0.14 ppm. Test chemical nominal conc. used for the study were1 mg/l and 0.1 mg/l (w/v), respectively. Range finding study involve the TLm (48 hr) 29.8 ppm (29.8 mg/l) (w/v) on Rice fish (Oryzias latipes). Lipid content of the test organism was determined to be 4.9%.The bioconcentration factor (BCF value) of substance 1 -methylpiperidine on Cyprinus carpio was determined to be 0.5 -1.2 at a conc. of 1 mg/l and 2.6 -6.3 L/Kg at a conc. of 0.1 mg/l, respectively.

 

Another bioaccumulation study was conducted for estimating the BCF (bioaccumulation factor) value of read across chemical 2,2'-(methylimino)diethanol (CAS no. 105-509-9) (HSDB, 2017). The bioaccumulation factor (BCF) value was calculated using an estimated log Kow of -1.50 and a regression derived equation. The BCF (bioaccumulation factor) value of 2,2'-(methylimino)diethanol was determined to be 3.2 dimensionless.

 

On the basis of above results for target chemical 4-chloro-1-methylpiperidine (from EPI Suite, ACD labs,ChemSpider, SciFinder database and CompTox Chemistry Dashboard,2017) and for its read across substance from authoritative database J-CHECK and HSDB, it can be concluded that the BCF value of test substance 4-chloro-1-methylpiperidine ranges from 1 –12.2 which does not exceed the bioconcentration threshold of 2000, indicating that the chemical 4-chloro-1-methylpiperidine is not expected to bioaccumulate in the food chain.

Adsorption/desorption

The adsorption coefficient Koc in soil and in sewage sludge 4-chloro-1-methylpiperidine (CAS No.5570 -77 -4) was determined by the Reverse Phase High Performance Liquid Chromatographic method according to OECD Guideline No. 121 for testing of Chemicals (Sustainability Support Services (Europe) AB, Report no. 5570-77-4/01/2017/Koc, 2017).The solutions of the test substance and reference substances were prepared in appropriate solvents. A test item solution was prepared by accurately measuring 4 μL of test item and diluted with acetonitrile up to 10 ml. Thus, the test solution concentration was 416 mg/l. The pH of test substance was 8.48. Each of the reference substance and test substance were analysed by HPLC at 210 nm. After equilibration of the HPLC system, Urea was injected first, the reference substances were injected in duplicate, followed by the test chemical solution in duplicate. Reference substances were injected again after test sample, no change in retention time of reference substances was observed. Retention time tR were measured, averaged and the decimal logarithms of the capacity factors k were calculated. The graph was plotted between log Koc versus log k(Annex - 2).The linear regression parameter of the relationship log Koc vs log k were also calculated from the data obtained with calibration samples and therewith, log Koc of the test substance was determined from its measured capacity factor. The reference substances were chosen according to estimated Koc range of the test substance and generalized calibration graph was prepared. The reference substances were having Koc value ranging from 1.25 to 4.09. The Log Koc value was determined to be 1.8537 ± 0.0093 at 25°C. This log Koc value indicates that the substance 4-chloro-1-methylpiperidine has a low sorption to soil and sediment and therefore have moderate migration potential to ground water.