3-(diethylamino)-7-imino-7H-[1]benzopyrano[3',2':3,4]pyrido[1,2-a]benzimidazole-6-carbonitrile

Endpoint summary

Description of key information

Biodegradation in water

Estimation Programs Interface Suite was run to predict the biodegradation potential of the test compound 3 -(diethylamino)-7 -imino-7H-chromeno[3',2':3,4]pyrido[1,2 -a]benzimidazole-6 -carbonitrile (CAS no. 52372 -39 -1) 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 as Biowin 1-7, respectively) of the BIOWIN v4.10 software. The results indicate that chemical 3 -(diethylamino)-7 -imino-7H-chromeno[3',2':3,4]pyrido[1,2 -a]benzimidazole-6 -carbonitrile is expected to be not readily biodegradable.

Bioaccumulation: aquatic / sediment

BCFBAF model of Estimation Programs Interface was used to predict the bioconcentration factor (BCF) of test chemical 3 -(diethylamino)-7 -imino-7H-chromeno [3',2':3,4]pyrido[1,2 -a]benzimidazole-6 -carbonitrile (CAS No. 52372 -39 -1). The bioconcentration factor (BCF) of 3 -(diethylamino)-7 -imino-7H-chromeno[3',2':3,4] pyrido[1,2 -a] benzimidazole-6 -carbonitrile was estimated to be 11.01 L/kg whole body w.w (at 25 deg C) which does not exceed the bio concentration threshold of 2000, indicating that the chemical 3 -(diethylamino)-7 -imino-7H-chromeno[3',2':3,4]pyrido[1,2 -a]benzimidazole-6 -carbonitrile is not expected to bioaccumulate in the food chain.

Adsorption / desorption

KOCWIN model of Estimation Programs Interface was used to predict the soil adsorption coefficient i.e Koc value of test chemical 3 -(diethylamino)-7 -imino-7H-chromeno[3',2':3,4]pyrido [1,2 -a]benzimidazole-6 -carbonitrile (CAS No. 52372 -39 -1). The soil adsorption coefficient i.e Koc value of 3 -(diethylamino)-7 -imino-7H-chromeno [3',2':3,4]pyrido[1,2 -a]benzimidazole-6 -carbonitrile was estimated to be 122500 L/kg (log Koc= 5.0880) by means of MCI method (at 25 deg C). This Koc value indicates that the substance 3 -(diethylamino)-7 -imino-7H-chrome no[3',2':3,4]pyrido[1,2 -a]benzimidazole-6 -carbonitrile has a very strong sorption to soil and sediment and therefore have negligible migration potential to ground water.

Additional information

Biodegradation in water

Predicted data for the target compound 3-(diethylamino)-7-imino-7H-chromeno[3',2':3,4]pyrido[1,2-a]benzimidazole-6-carbonitrile (CAS No. 52372-39-1) and various supporting weight of evidence studies for its structurally and functionally similar read across substance were reviewed for the biodegradation end point which are summarized as below:

 

In a prediction using the Estimation Programs Interface Suite (2018), the biodegradation potential of the test compound 3 -(diethylamino)-7 -imino-7H-chromeno[3',2':3,4]pyrido[1,2 -a]benzimidazole-6 -carbonitrile (CAS No. 52372-39-1) 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 3 -(diethylamino)-7 -imino-7H-chrome no[3',2':3,4]pyrido[1,2 -a]benzimidazole-6 -carbonitrile is expected to be not readily biodegradable.

 

For the test chemical, biodegradation study was conducted for 5 days for evaluating the percentage biodegradability of test substance using standard dilution method at a temperature of 20°C (H. Heukelekian et. al., 1955). Sewage was used as a test inoculum. The 5 day BOD value of test chemical was determined to be 0 g/g. Thus, based on this value, test substance is considered to be not readily biodegradable in nature.

 

In a supporting weight of evidence study from authoritative database (2017) for the test chemical,biodegradation study was conducted for 14 days for evaluating the percentage biodegradability of test substance. 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 test substance was determined to be 0% by BOD parameter in 14 days. Thus, based on percentage degradation, test chemical is considered to be not readily biodegradable in nature.

 

Another biodegradation study was conducted for 5 days for evaluating the percentage biodegradability of test chemical. Sewage sludge was used as a test inoculum. The percentage degradation of test substance was determined to be 5% by BOD parameter in 5 days. Thus, based on percentage degradation, test chemical is considered to be not readily biodegradable in nature.

 

In a supporting weight of evidence study from authoritative database (2017) for the test chemical,biodegradation experiment was conducted for 28 days for evaluating the percentage biodegradability of test substance. Activated sludge (non-adapted) was used as a test inoculums for the study. 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 test substance was determined to be 1% by BOD and HPLC parameter in 28 days. Thus, based on percentage degradation, test chemical is considered to be not readily biodegradable in nature.

 

On the basis of above results for target chemical 3-(diethylamino)-7-imino-7H-chromeno[3',2':3,4]pyrido[1,2-a]benzimidazole-6-carbonitrile (from modelling database, 2018), it can be concluded that the test substance 3-(diethylamino)-7-imino-7H-chromeno[3',2':3,4]pyrido[1,2-a]benzimidazole-6-carbonitrile can be expected to be not readily biodegradable in nature.

Bioaccumulation: aquatic / sediment

Various predicted data for the target compound 3-(diethylamino)-7-imino-7H-chromeno[3',2':3,4]pyrido[1,2-a]benzimidazole-6-carbonitrile (CAS No. 52372-39-1) and supporting weight of evidence study for its structurally and functionally similar read across substance were reviewed for the bioaccumulation end point which are summarized as below:

 

In aprediction done using theBCFBAF Programof Estimation Programs Interface was used to predict the bioconcentration factor (BCF) of test chemical 3 -(diethylamino)-7 -imino-7H-chromeno [3',2':3,4]pyrido[1,2 -a]benzimidazole-6 -carbonitrile (CAS No. 52372 -39 -1). The bioconcentration factor (BCF) of 3 -(diethylamino)-7 -imino-7H-chromeno[3',2':3,4] pyrido[1,2 -a] benzimidazole-6 -carbonitrile was estimated to be 11.01 L/kg whole body w.w (at 25 deg C).

 

From CompTox Chemistry Dashboard using OPERA (OPEn (quantitative) structure-activity Relationship Application) in which calculation based on PaDEL descriptors (calculate molecular descriptors and fingerprints of chemical), the bioaccumulation i.e BCF for test substance 3 -(diethylamino)-7 -imino-7H-chromeno[3',2':3,4]pyrido[1,2 -a]benzimidazole-6 -carbonitrile was estimated to be 31.1 dimensionless . The predicted BCF result based on the 5 OECD principles.

 

In a supporting weight of evidence study from authoritative database (2017) for the test item,bioaccumulation experiment was conducted on test organism Cyprinus carpio for 8 weeks for evaluating the bioconcentration factor (BCF value) of test chemical 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. HCO-40 was used as a vehicle. Test chemical nominal conc. used for the study were 0.2 mg/l and 0.02 mg/l (w/v), respectively. Range finding study involve the TLm (48 hr) of 16.8 ppm (16.8 mg/l) (w/v) on Rice fish (Oryzias latipes). The bioconcentration factor (BCF value) of test chemical on Cyprinus carpio was determined to be 44 and 161 L/Kg at a conc. of 0.2 mg/l and 17 and 125 L/Kg at a conc. of 0.02 mg/l, respectively, which does not exceed the bioconcentration threshold of 2000, indicating that the test chemical is not expected to bioaccumulate in the food chain.

 

For the test chemical,bioaccumulation study was conducted on test organism Cyprinus carpio for 28 days for evaluating the bioconcentration factor (BCF value) of test chemical (authoritative database, 2018). The study was performed according to OECD Guideline 305 C (Bioaccumulation: Test for the Degree of Bioconcentration in Fish) and 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. Test chemical nominal conc. used for the study was 0.05 mg/l and 0.005 mg/l, respectively. Test chemical solution was prepared in N,N-Dimethylformamide. Analytical method involve the recovery ratio: Test water : 100 % (Only dilution was conducted as the pretreatment in the test water analysis), Fish : 96.0 %, - Limit of quantitation : Test water : 1st concentration area : 2.5 microg/L, 2nd concentration area : 0.25 microg/L, Fish : 25 ng/g.Range finding study involve theLC50(96h) > 5.00 mg/L(w/v) on Rice fish (Oryzias latipes). Lipid content of the test organism Cyprinus carpio was determined to be1.58 and 2.43% at the start and end of exposure. The bioconcentration factor (BCF value) of test substance on Cyprinus carpio was determined to be ≤ 0.49 L/Kg at a conc. of 0.05 mg/l and ≤ 5 L/Kg at a conc. of 0.005 mg/l, respectively, which does not exceed the bioconcentration threshold of 2000, indicating that the test chemical is not expected to bioaccumulate in the food chain.

 

On the basis of above results for target chemical 3-(diethylamino)-7-imino-7H-chromeno[3',2':3,4]pyrido[1,2-a]benzimidazole-6-carbonitrile (from modelling databases,2017), it can be concluded that the BCF value of test substance 3-(diethylamino)-7-imino-7H-chromeno[3',2':3,4]pyrido[1,2-a]benzimidazole-6-carbonitrile ranges from 11.01 –31.1which does not exceed the bioconcentration threshold of 2000, indicating that the chemical 3-(diethylamino)-7-imino-7H-chromeno[3',2':3,4]pyrido[1,2-a]benzimidazole-6-carbonitrile is not expected to bioaccumulate in the food chain.

Adsorption / desorption

Various predicted data for the target compound 3-(diethylamino)-7-imino-7H-chromeno[3',2':3,4]pyrido[1,2-a]benzimidazole-6-carbonitrile (CAS No. 52372-39-1) and supporting weight of evidence study for its structurally and functionally similar read across substance were reviewed for the adsorption end point which are summarized as below:

 

In aprediction done using theKOCWIN Programof Estimation Programs Interface was used to predict the soil adsorption coefficient i.e Koc value of test chemical 3 -(diethylamino)-7 -imino-7H-chromeno[3',2':3,4]pyrido[1,2 -a]benzimidazole-6 -carbonitrile (CAS No. 52372 -39 -1). The soil adsorption coefficient i.e Koc value of 3 -(diethylamino)-7 -imino-7H-chromeno [3',2':3,4]pyrido[1,2 -a]benzimidazole-6 -carbonitrile was estimated to be 122500 L/kg (log Koc= 5.0880) by means of MCI method (at 25 deg C). This Koc value indicates that the substance 3-(diethylamino)-7-imino-7H-chromeno[3',2':3,4]pyrido[1,2-a]benzimidazole-6-carbonitrile has a very strong sorption to soil and sediment and therefore have negligible migration potential to ground water.

 

The Soil Adsorption Coefficient i.e Koc value of test substance 3-(diethylamino)-7-imino-7H-chromeno[3',2':3,4]pyrido[1,2-a]benzimidazole-6-carbonitrile (CAS no. 52372 -39 -1) was estimated using Adsorption Coefficient program as Koc 11.1, 33.8, 65.0, 138, 790, 5553, 15998, 19741, 20215, 20264, 20268 and 20269 at pH range 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 and 11-14 respectively (log Koc value ranges from 1.0 ± 1.0 to 4.3 ± 1.0) (modelling database, 2017). The Koc value (at pH 7.0) indicates that the substance 3 -(diethylamino)-7 -imino-7H-chromeno [3',2':3,4]pyrido[1,2 -a]benzimidazole-6 -carbonitrile has a strong sorption to soil and sediment and therefore have negligible to slow migration potential to ground water.

 

In an another prediction done by using ChemSpider Database (2017), theSoil Adsorption Coefficient i.e Koc value of test substance 3-(diethylamino)-7-imino-7H-chromeno[3',2':3,4]pyrido[1,2-a]benzimidazole-6-carbonitrile (CAS no. 52372 -39 -1) was estimated. The adsorption coefficient (Koc) value of test substance 3 -(diethylamino)-7 -imino-7H-chromeno[3',2':3,4]pyrido[1,2 -a]benzimidazole-6 -carbonitrile was estimated to be 7136.58 (Log Koc = 3.853) at pH 5.5 and 12565.31 (Log Koc = 4.099) at 7.4, respectively. This Koc value indicates that the substance 3 -(diethylamino)-7 -imino-7H-chromeno[3',2':3,4]pyrido[1,2 -a]benzimidazole-6 -carbonitrile has a strong sorption to soil and sediment and therefore have negligible to slow migration potential to ground water.

 

Additional soil adsorption coefficient i.e Koc value of test chemical3 -(diethylamino)-7 -imino-7H-chrom eno[3',2':3,4]pyrido[1,2 -a]benzimidazole-6 -carbonitrile (CAS No. 52372 -39 -1)was estimated using the SciFinder database (2017).The soil adsorption coefficient i.e Koc value of 3 -(diethylamino)-7 -imino-7H-chromeno[3',2':3,4] pyrido[1,2 -a]benzimidazole-6 -carbonitrile was estimated to be 1070, 2580, 5680, 31900, 228000, 684000, 858000, 880000, 882000 and 883000 at pH range 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10, respectively (at 25 deg C) (log Koc value ranges from 3.029 to 5.945). The Koc value (at pH 7.0) indicates that the substance 3 -(diethylamino)-7 -imino-7H- chromeno[3',2':3,4]pyrido[1,2 -a]benzimidazole-6 -carbonitrile has a very strong sorption to soil and sediment and therefore have negligible migration potential to ground water.

 

From CompTox Chemistry Dashboard using OPERA (OPEn (quantitative) structure-activity Relationship Application) model in which calculation based on PaDEL descriptors (calculate molecular descriptors and fingerprints of chemical), the adsorption coefficient i.e KOC for test substance 3 -(diethylamino)-7 -imino-7H-chromeno[3',2':3,4]pyrido[1,2 -a]benzimidazole-6 -carbonitrile was estimated to be 135000 L/kg (log Koc = 5.13).The predicted KOC result based on the 5 OECD principles. This Koc value indicates that the substance 3-(diethylamino)-7-imino-7H-chromeno[3',2':3,4]pyrido[1,2-a]benzimidazole-6-carbonitrile has a very strong sorption to soil and sediment and therefore have negligible migration potential to ground water.

 

In a supporting weight of evidence study from study report (2018) for the test item,the adsorption coefficient Koc in soil and in sewage sludge of test chemical was determined by the Reverse Phase High Performance Liquid Chromatographic method according to OECD Guideline No. 121 for testing of Chemicals. The solutions of the test substance and reference substances were prepared in appropriate solvents. A test item solution was prepared by accurately weighing 50mg of test item and diluted with mobile phase up to 100ml. Thus, the test solution concentration was 500mg/l. The pH of test substance was 7.90. 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. T The reference substances were chosen according to structural similarity with the test substance and calibration graph was prepared. The reference substances were 4 – Toluidine, N-methylaniline, Toluene, Naphthalene, Phenanthrene and DDDT having Koc value ranging from 1.9 to 5.63.The Log Koc value of test chemical was determined to be 3.594 ± 0.003 at 25°C. This log Koc value indicates that the test substance has a strong sorption to soil and sediment and therefore have negligible to slow migration potential to ground water.

 

On the basis of above overall results for target chemical 3-(diethylamino)-7-imino-7H-chromeno[3',2':3,4]pyrido[1,2-a]benzimidazole-6-carbonitrile (from modelling databases,2017), it can be concluded that the Koc value of test substance 3-(diethylamino)-7-imino-7H-chromeno[3',2':3,4]pyrido[1,2-a]benzimidazole-6-carbonitrile was estimated to be 12565.31 to 858000.0 (logKoc ranges from 4.099 to 5.933 at pH 7.0) indicating that the test chemical 3-(diethylamino)-7-imino-7H-chromeno[3',2':3,4]pyrido[1,2-a]benzimidazole-6-carbonitrile has a strong to very strong sorption to soil and sediment and therefore have negligible to slow migration potential to ground water.