N-(4-chlorobenzhydryl)piperazine

Endpoint summary

Description of key information

Stability:

Hydrolysis:

The half life of hydrolysis of test chemical 1-[(4-chlorophenyl)(phenyl)methyl]piperazine was estimated by using OECD QSAR tool box v3.3 and closest read across chemicals with log Kow as primary descriptor. The half life of hydrolysis of test chemical 1-[(4-chlorophenyl)(phenyl)methyl]piperazine was estimated to be 244.66 days. Based on half life of hydrolysis value it is concluded that this test chemical is not hydrolysable.

Biodegradation:

Biodegradation in water:

Percent biodegradability of test chemical 1-[(4-chlorophenyl)(phenyl)methyl]piperazine (CAS no. 303-26-4) was estimated by using OECD QSAR tool box v3.3 using Log Kow as primary descriptor. Percent biodegradation of test chemical 1-[(4-chlorophenyl)(phenyl)methyl]piperazine was determined to be 1 % by considering BOD as parameter  and microorganisms as inoculum in 28 days. Based on % biodegrdability value it is concluded that this test chemical in not readily biodegradable.

Biodegradation in water and sediments:

Estimation Programs Interface (EPI Suite, 2017) prediction model was run to predict the half-life in water and sediment for the test compound1-[(4-chlorophenyl)(phenyl)methyl]piperazine(CAS No. 303 -26 -4). If released in to the environment, 6.01% of the chemical will partition into water according to the Mackay fugacity model level III and the half-life period of test chemical in water is estimated to be60 days (1440 hrs). The half-life (60 days estimated by EPI suite) indicates that the chemical is persistent in water and the exposure risk to aquatic animals is high whereas the half-life period of test chemical1-[(4-chlorophenyl)(phenyl)methyl]piperazinein sediment is estimated to be 541.66 days (3240 hrs).  This Half life value in sediment indicates that test chemical1-[(4-chlorophenyl)(phenyl)methyl]piperazine is persistent in sediment as well.

Biodegradation in Soil:

The half-life period of test chemical1-[(4-chlorophenyl)(phenyl)methyl]piperazine(CAS No. 303 -26 -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 % of the chemical will partition into soil according to the Mackay fugacity model level III. The half-life period of test chemical1-[(4-chlorophenyl)(phenyl)methyl]piperazinein soil is estimated to be 120 days (2800 hrs). Based on this half-life value of test chemical1-[(4-chlorophenyl)(phenyl)methyl]piperazine, it is concluded that the chemical is not persistent in the soil environment and the exposure risk to soil dwelling animals is low.

Bioaccumulation:

Bioaccumulation:aquatic/sediments:

Using BCFBAF Program (v3.00) model of EPI suite (2017) the estimated bio concentration factor (BCF) for 1-[(4-chlorophenyl)(phenyl)methyl]piperazine (CAS No. 303-26-4) is 98.88 L/kg wet-wt at 25 deg. c which does not exceed the bioconcentration threshold of 2000. Therefore it is concluded that test chemical 1-[(4-chlorophenyl)(phenyl)methyl]piperazine is non bioaccumulative in food chain.

Transport and distribution:

Adsorption/desorption:

The Soil Adsorption Coefficient i.e Koc value of test substance1-[(4-chlorophenyl)(phenyl)methyl]piperazine was estimated using Adsorption Coefficient module (v12.1.0.50374) program at pH 6 as Koc 3.40 dimensionless (log Koc= 0.5)  at pH 7 Koc 21.0 dimensionless (log Koc=1.3) and at pH 8 Koc 180 dimensionless (log Koc=2.3).These log Koc values indicate that the test substance1-[(4-chlorophenyl)(phenyl)methyl]piperazinehas a negligible to low sorption to soil and therefore have rapid to moderate migration potential to groundwater.

Additional information

Stability:

Hydrolysis:

Predicted data study for target chemical chemical 1-[(4-chlorophenyl)(phenyl)methyl]piperazine and two experimental studies for its structurally similar read across cchemical have been conducted and their results are summarized below.

In first weight of evidence study the half life of hydrolysis of test chemical 1-[(4-chlorophenyl)(phenyl)methyl]piperazine was estimated by using OECD QSAR tool box v3.3 and closest read across chemicals with log Kow as primary descriptor. The half life of hydrolysis of test chemical 1-[(4-chlorophenyl)(phenyl)methyl]piperazine was estimated to be 244.66 days. Based on half life of hydrolysis value it is concluded that this test chemical is not hydrolysable.

Next weight of evidence study was done by using authoritative database (HSDB, 2017) in this study the read across chemical 2-[2-[4-[(4-chlorophenyl)-phenyl-methyl]piperazin-1-yl]ethoxy]acetic acid (CAS no.83881-51-0) is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions On the basis of this it is concluded that this read across chemical is not hydrolysable.

Last weight of evidence study was also done from authoritative database (HSDB, 2017) in study another read across chemical 1-(2-Aminoethyl) piperazine (CAS no.140-31-8) is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions On the basis of this it is concluded that this read across chemical is not hydrolysable.

On the basis of all the studies mentioned above it can be concluded that target chemical1-[(4-chlorophenyl)(phenyl)methyl]piperazine (CAS no. 303-26-4) is not hydrolysable.

Biodegradation:

Biodegradation in water :

Predicted data studies for target chemical chemical 1-[(4-chlorophenyl)(phenyl)methyl]piperazine (CAS no. 303-26-4)and experimental studies for its read across chemicals have been studied and their results are summarized below for biodegradation water endpoint.

In first weight of evidence study the Percent biodegradability of test chemical 1-[(4-chlorophenyl)(phenyl)methyl]piperazine (CAS no. 303-26-4) was estimated by using OECD QSAR tool box v3.3 using Log Kow as primary descriptor. Percent biodegradation of test chemical 1-[(4-chlorophenyl)(phenyl)methyl]piperazine was determined to be 1 % by considering BOD as parameter  and microorganisms as inoculum in 28 days. Based on % biodegrdability value it is concluded that this test chemical in not readily biodegradable.

 

Second weight of evidence study was done by using Estimation Programs Interface Suite (EPI suite, 2017) to estimate the biodegradation potential of the test compound 1-[(4-chlorophenyl)(phenyl)methyl]piperazine (CAS no. 303 -26 -4) in the presence of mixed populations of environmental microorganisms. 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 Biowin 1-7, respectively) of the BIOWIN v4.10 software. The results indicate that chemical  1-[(4-chlorophenyl)(phenyl)methyl]piperazine is expected to be not readily biodegradable.

Next weight of evidence study was done from authoritative database (J Check, 2017) for structurally similar read across chemical in this study the biodegradation experiment was conducted for 14 days for evaluating the percentage biodegradability of read across substance Piperazine (CAS No: 110-85-0).Concentration of inoculum i.e, sludge used was 30 mg/l and initial test substance conc. used in the study was 100 mg/l. The percentage degradation of read across substance obtained was 1.4% by BOD, 1% by TOC removal and 2.8% by GC parameter in 14 days. Thus, read across substance Piperazine (CAS No: 110-85-0) is considered to be not readily biodegradable in water.

Last weight of evidence study was also done from same source as mentioned above for red across chemical in this study the read across chemical 1-methyl-diethylenediamine (CAS no. 109-01-3) was subjected to biodegradation test by taking sludge as inoculums at 30 mg/L concentration. Biodegradation was analysed by using O2 Consumption, DOC removal and test material analysis by HPLC parameters. The initial concentration of read across chemical was 100 mg/L. After 4 weeks (28 days) test chemical showed 0% biodegradation by all three parameters mentioned above so it is concluded that this read across chemical 1-methyl-diethylenediamine is not readily biodegradable.

On the basis of results of above mentioned studies for target chemical 1-[(4-chlorophenyl)(phenyl)methyl]piperazine( from OECD QSAR tool boxv3.3 and EPI suite) and supporting weight of evidence study ( from J Check, 2017). It is concluded that the test chemical 1-[(4-chlorophenyl)(phenyl)methyl]piperazine can be expected to be not readily biodegradable.

Biodegradation in water and sediments:

Estimation Programs Interface (EPI Suite, 2017) prediction model was run to predict the half-life in water and sediment for the test compound 1-[(4-chlorophenyl)(phenyl)methyl]piperazine(CAS No. 303 -26 -4). If released in to the environment, 6.01% of the chemical will partition into water according to the Mackay fugacity model level III and the half-life period of test chemical in water is estimated to be 60 days (1440 hrs). The half-life (60 days estimated by EPI suite) indicates that the chemical is persistent in water and the exposure risk to aquatic animals is high whereas the half-life period of test chemical 1-[(4-chlorophenyl)(phenyl)methyl]piperazinein sediment is estimated to be 541.66 days (3240 hrs). This Half life value in sediment indicates that test chemical 1-[(4-chlorophenyl)(phenyl)methyl]piperazine is persistent in sediment as well.

Biodegradation in Soil:

The half-life period of test chemical 1-[(4-chlorophenyl)(phenyl)methyl]piperazine (CAS No. 303 -26 -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 % of the chemical will partition into soil according to the Mackay fugacity model level III. The half-life period of test chemical 1-[(4-chlorophenyl)(phenyl)methyl]piperazinein soil is estimated to be 120 days (2800 hrs). Based on this half-life value of test chemical 1-[(4-chlorophenyl)(phenyl)methyl]piperazine, it is concluded that the chemical is not persistent in the soil environment and the exposure risk to soil dwelling animals is low .

Bioaccumulation:

Bioaccumulation:aquatic/sediments:

Various predicted data for the target compound1-[(4-chlorophenyl)(phenyl)methyl]piperazine (CAS No. 303-26-4)and supporting weight of evidence study for its read across chemical were reviewed for the bioaccumulation end point which are summarized as below:

First weight of evidence study was done by using BCFBAF Program (v3.00) model of Estimation Program Interface suite (2017) the estimated bio concentration factor (BCF) for 1-[(4-chlorophenyl)(phenyl)methyl]piperazine (CAS No. 303-26-4) is 98.88 L/kg wet-wt at 25 deg. c which does not exceed the bioconcentration threshold of 2000.

Next predicted data study was done by using Bio-concentration Factor (v12.1.0.50374) module of(ACD (Advanced Chemistry Development)/I-Lab predictive module, 2017) module in this study theBio-concentration Factor at pH 7 of the chemical 1-[(4-chlorophenyl)(phenyl)methyl]piperazine (CAS no.303 -26 -4) estimated to be 2.88 dimensionless.

Another predicted data study was done by using Scifinder database of(American Chemical Society (ACS), 2017) in this studythe Bioconcentration factor (BCF) of test substance 1-[(4-chlorophenyl)(phenyl)methyl]piperazine at pH 1 -7 range and temperature 25 °C was estimated to be 1 dimensionless and at pH 8, 9 and 10 BCF values was estimate to be 7.18, 49.7 and 125 dimensionless respectively.

 

Next weight of evidence study was done by Using Chemspider-ACD/Phychem suite prediction model of Royal Society of Chemistry (2017) in this studythe Bioconcentration factor (BCF) for test chemical1-[(4-chlorophenyl)(phenyl)methyl]piperazine (CAS No: 303-26-4) was predicted in aquatic organisms by  at pH 5.5 and pH 7.4.The Bioconcentration factor (BCF) of test substance1-[(4-chlorophenyl)(phenyl)methyl]piperazine at pH 5.5 was estimated to be 1 dimensionless and pH 7.4 was estimated to be 15.06 dimensionless. 

Another weight of evidence study was done 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 1-[(4-chlorophenyl)(phenyl)methyl]piperazine (CAS no.303 -26 -4) was estimated to be 60.8 dimensionless. The predicted BCF result was based on the 5 OECD principles.

In a supporting weight of evidence study the Bioaccumulation study was conducted on test organism Cyprinus carpio for 6 weeks for evaluating the bioconcentration factor (BCF value) of red across Piperazine (CAS no.110-85-0) from authoritative database (J check, 2017).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", respectively. Cyprinus carpio was used as a test organism for the study. Read across chemical nominal conc. used for the study were 1mg/l and 0.1 mg/l, respectively. Range finding study involve the TLm (48 hr) ≥ 1000 mg/l (w/v) on Rice fish (Oryzias latipes).The bioconcentration factor (BCF value) of substance Piperazine on Cyprinus carpio was determined to be ≤ 0.3 – 0.9 L/Kg at a conc. of 1 mg/l and ≤ 3.9 L/Kg at a conc. of 0.1 mg/l, respectively, which does not exceed the bioconcentration threshold of 2000, indicating that the red across chemical Piperazine is not expected to bioaccumulate in the food chain.

Last weight of evidence study was also supporting study done from authoritative database (HSDB, 2017) in this study the BCF value of read across chemical 2-[2-[4-[(4-chlorophenyl)-phenyl-methyl]piperazin-1-yl]ethoxy]acetic acid (CAS no. 83881-51-0) estimated was 3 dimensionless by using log Kow of 1.70 and regression derived equation and it is far less than 2000 criteria so it is concluded that test chemical 2-[2-[4-[(4-chlorophenyl)-phenyl-methyl]piperazin-1-yl]ethoxy]acetic acid is non bioaccumulative.

On the basis of above results for target chemical 1-[(4-chlorophenyl)(phenyl)methyl]piperazine (CAS No. 303-26-4) (from EPI suite, ACD labs, Sci Finder database, Chemspider and CompTox Chemistry Dashboard 2017) and for its read across chemicals (From HSDB and J check) it can be concluded that the BCF value of test substance 1-[(4-chlorophenyl)(phenyl)methyl]piperazine ranges from 1-125 dimensionless which does not exceed the bioconcentration threshold of 2000, indicating that the chemical 1-[(4-chlorophenyl)(phenyl)methyl]piperazine is expected to be non-bioaccumulative in the food chain.

Transport and distribution:

Adsorption/desorption:

Various predicted data for the target compound of 1-[(4-chlorophenyl)(phenyl)methyl]piperazine and supporting weight of evidence study for its read across chemical were reviewed for the Adsorption end point are summarized as below.

In a prediction done using Bio-concentration Factor (v12.1.0.50374) (ACD (Advanced Chemistry Development)/I-Lab predictive module, 2017) modulethe Soil Adsorption Coefficient i.e Koc value of test substance 1-[(4-chlorophenyl)(phenyl)methyl]piperazine was estimated using Adsorption Coefficient module (v12.1.0.50374) program at pH 6 as Koc 3.40 dimensionless (log Koc= 0.5)  at pH 7 Koc 21.0 dimensionless (log Koc=1.3) and at pH 8 Koc 180 dimensionless (log Koc=2.3). These log Koc values indicate that the test substance 1-[(4-chlorophenyl)(phenyl)methyl]piperazine has a negligible to low sorption to soil and therefore have rapid to moderate migration potential to groundwater.

Another predicted data was estimated using Sci Finder database (American Chemical Society (ACS), 2017) in this studythe soil adsorption co-efficient i.e., Koc value of test chemical 1-[(4-chlorophenyl)(phenyl)methyl]piperazine  at pH 1-4 was estimated to be1 dimensionless ( log Koc = 0)  at temperature 25 deg.c.and at pH 5-10 Koc values was estimated to be 1.06, 1.62, 7.18, 60.2, 417,1040 dimensionless (log koc=0.0253,0.2095,0.8561,1.7795,2.6201, and 3.0170) respectively. By considering koc value at pH 7 which is 7.18 (log Koc=0.8561)   it is concluded that this test chemical has negligible sorption to soil and threrfore have rapid migration potential to ground water at pH 7.

Next weight of evidence study was done by Using Chemspider-ACD/Phy chem suite of Royal society of Chemistry (RCS, 2017) in this study the soil adsorption co-efficient i.e., Koc value of test substance 1-[(4-chlorophenyl)(phenyl)methyl]piperazine was estimated to be 3.29 dimensionless (log Koc= 0.5550) at pH 5.5 and  at 7.4  Koc value was estimated to be 87.78 (log Koc=1.9433) and temperature 25 deg.C These Koc values at different pH indicate that the chemical 1-[(4-chlorophenyl)(phenyl)methyl]piperazine has negligible to low sorption to soil and sediments and therefore test chemical has rapid to moderate migration potential to ground water.

Next weight of evidence study was done from HSDB authoritative database (2017) in this study the adsorption coefficient (Koc) of red across substance Piperazine was determined to be 3.6 (log Koc= 0.5563) using a log Kow of 1.50 and a regression derived equation. This Koc value suggests that piperazine is expected to have very high mobility in soil.

Another weight of evidence study was done fromEuropean Union Risk Assessment Report 2005 fror read cross chemical piperazine in this report adsorption study was performed with three different soils (loam, sand and sandy loam) using the batch equilibrium method (OECD Guidelines 106) (Geurts, 2003). The optimal soil solution ratio of 1:5 was used for the final sorption test. Equilibrium was reached after approximately 8 hours. During experiment the Kd values was determined to be 7.9-20 these results indicate that sorption of piperazine to soil is not correlated to the organic carbon content of the soils. Thus study finally concluded that the test chemical does not meant to be to adsorb to or partition into solids to any significant extent, but remained in the water phase.

Last weight of evidence study was also done from authoritative database (HSDB, 2017) for read cross chemical 2-[2-[4-[(4-chlorophenyl)-phenyl-methyl]piperazin-1-yl]ethoxy]acetic acid(CAS no.83881-51-0) the Koc value for chemical 2-[2-[4-[(4-chlorophenyl)-phenyl-methyl]piperazin-1-yl]ethoxy]acetic acid was determined by a log Kow of 1.70 and a regression-derived equation. The estimated Koc value was 200 dimensionless and log Koc is 2.3010 this log Koc value suggests that 2-[2-[4-[(4-chlorophenyl)-phenyl-methyl]piperazin-1-yl]ethoxy]acetic acidis expected to have low sorption to soil and sediment and therefore has moderate migration potential to ground water.

On the basis of above results for target chemical1-[(4-chlorophenyl)(phenyl)methyl]piperazine(from ACD labs, Sci Finder database, and Chemspider 2017) and for its read across chemicals (From authoritative database HSDB and European Union Risk Assessment Report) it can be concluded that the log Koc value of test chemical 1-[(4-chlorophenyl)(phenyl)methyl]piperazine ranges from0.8561to1.9433indicating that the chemical 1-[(4-chlorophenyl)(phenyl)methyl]piperazine has negligible to low sorption to soil and sediment and therefore it has rapid to moderate migration potential to ground water