12H-phthaloperin-12-one

Endpoint summary

Description of key information

Hydrolysis

On the basis of the experimental studies of the test chemical and applying the weight of evidence approach, the hydrolysis half-life value of the test chemical can be expected to be 44 days at pH 5.0 and it was reported to be hydrolytically stable at pH 7 & 9, respectively or 622 days at pH 4 and at a temperature of 25⁰C. Thus, based on this half-life value, it can be concluded that the test chemical is not hydrolysable.

Biodegradation in water

42-days Closed Bottle test following the OECD guideline 301 D was performed to determine the ready biodegradability of the test chemical (Experimental study report, 2018). The study was performed at a temperature of 20°C. The test system included control, test item and reference item. Polyseed were used for this study. 1 polyseed capsule were added in 500 ml D.I water and then stirred for 1 hour for proper mixing and functioning of inoculum. This gave the bacterial count as 10E7 to 10E8 CFU/ml. At the regular interval microbial plating was also performed on agar to confirm the vitality and CFU count of microorganism. The concentration of test and reference item (Sodium Benzoate) chosen for both the study was 4 mg/L, while that of inoculum was 32 ml/l. OECD mineral medium was used for the study. ThOD (Theoretical oxygen demand) of test and reference item was determined by calculation. % degradation was calculated using the values of BOD and ThOD for test item and reference item. The % degradation of procedure control (reference item) was also calculated using BOD & ThOD and was determined to be 70.48%. Degradation of Sodium Benzoate exceeds 45.18 % on 7 days & 70.48 % on 14th day. The activity of the inoculum was thus verified and the test can be considered as valid. The BOD42 value of test chemical was observed to be 0.5 mgO2/mg. ThOD was calculated as 2.19 mgO2/mg. Accordingly, the % degradation of the test item after 42 days of incubation at 20 ± 1°C according to Closed Bottle test was determined to be 22.83%. Based on the results, the test item, under the test conditions, was considered to be primary inherently biodegradable in nature.

Biodegradation in water and sediment

Estimation Programs Interface (2018) prediction model was run to predict the half-life in water and sediment for the test chemical. If released in to the environment, 9.5% 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 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 test chemical in sediment is estimated to be 337.5 days (8100 hrs). Based on this half-life value, it indicates that test chemical is persistent in sediment.

Biodegradation in soil

The half-life period of test chemical in soil was estimated using Level III Fugacity Model by EPI Suite version 4.1 estimation database (2018). If released into the environment, 79.6% of the chemical will partition into soil according to the Mackay fugacity model level III. The half-life period of test chemical in soil is estimated to be 75 days (1800 hrs). Based on this half-life value of test chemical, 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 of Estimation Programs Interface was used to predict the bioconcentration factor (BCF) of test chemical. The bioconcentration factor (BCF) of test chemical was estimated to be 24.13 L/kg whole body w.w (at 25 deg C) which does not exceed the bio concentration threshold of 2000, indicating that the test chemical is not expected to bioaccumulate in the food chain.

Adsorption / desorption

The Adsorption Coefficient of test substance was determined as per the HPLC method (OECD Guideline-121). The Log Koc value was determined to be 3.498 ± 0.001 at 25°C.This log Koc value indicates that the test chemical has a strong sorption to soil and sediment and therefore have negligible to slow migration potential to ground water.

Additional information

Hydrolysis

Data available for the test chemical has been reviewed to determine the half-life of hydrolysis as a function of pH. The studies are as mentioned below:

 

The half-life of the test chemical was determined at different pH range. The study was performed at pH of 5, 7 and 9, respectively. The half-life period of test chemical was determined to be 44 days at pH 5.0 and test chemical was reported to be hydrolytically stable at pH 7 and 9, respectively.On the basis of this, test chemical is considered to be not hydrolysable.

 

The half-life of the test chemical was determined at different pH range. The study was performed according to OECD Guideline 111 (Hydrolysis as a Function of pH) at a temperature of 25°C and pH of 4, 7 and 9, respectively. The half-life period of test chemical was determined to be 622 days at pH 4, respectively. Thus, test chemical was reported to be hydrolytically stable at pH 4 and at a temperature of 25⁰C. On the basis of this, test chemical is considered to be not hydrolysable.

 

The half-life of the test chemical was determined. Although the hydrolysis half-life value of test chemical was not knownand as it has only 3-membered aromatic rings associated with its structure that is generally resistant to hydrolysis.Thus, test chemical was reported to be hydrolytically stable.

 

On the basis of the experimental studies of the test chemical and applying the weight of evidence approach, the hydrolysis half-life value of the test chemical can be expected to be 44 days at pH 5.0 and it was reported to be hydrolytically stable at pH 7 & 9, respectively or 622 days at pH 4 and at a temperature of 25⁰C. Thus, based on this half-life value, it can be concluded that the test chemical is not hydrolysable.

Biodegradation in water

42-days Closed Bottle test following the OECD guideline 301 D was performed to determine the ready biodegradability of the test chemical (Experimental study report, 2018). The study was performed at a temperature of 20°C. The test system included control, test item and reference item. Polyseed were used for this study. 1 polyseed capsule were added in 500 ml D.I water and then stirred for 1 hour for proper mixing and functioning of inoculum. This gave the bacterial count as 10E7 to 10E8 CFU/ml. At the regular interval microbial plating was also performed on agar to confirm the vitality and CFU count of microorganism. The concentration of test and reference item (Sodium Benzoate) chosen for both the study was 4 mg/L, while that of inoculum was 32 ml/l. OECD mineral medium was used for the study. ThOD (Theoretical oxygen demand) of test and reference item was determined by calculation. % degradation was calculated using the values of BOD and ThOD for test item and reference item. The % degradation of procedure control (reference item) was also calculated using BOD & ThOD and was determined to be 70.48%. Degradation of Sodium Benzoate exceeds 45.18 % on 7 days & 70.48 % on 14th day. The activity of the inoculum was thus verified and the test can be considered as valid. The BOD42 value of test chemical was observed to be 0.5 mgO2/mg. ThOD was calculated as 2.19 mgO2/mg. Accordingly, the % degradation of the test item after 42 days of incubation at 20 ± 1°C according to Closed Bottle test was determined to be 22.83%. Based on the results, the test item, under the test conditions, was considered to be primary inherently biodegradable in nature.

Biodegradation in water and sediment

Estimation Programs Interface (2018) prediction model was run to predict the half-life in water and sediment for the test chemical. If released in to the environment, 9.5% 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 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 test chemical in sediment is estimated to be 337.5 days (8100 hrs). Based on this half-life value, it indicates that test chemical is persistent in sediment.

Biodegradation in soil

The half-life period of test chemical in soil was estimated using Level III Fugacity Model by EPI Suite version 4.1 estimation database (2018). If released into the environment, 79.6% of the chemical will partition into soil according to the Mackay fugacity model level III. The half-life period of test chemical in soil is estimated to be 75 days (1800 hrs). Based on this half-life value of test chemical, 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 chemical can be considered to be primary inherently biodegradable in nature.

Bioaccumulation: aquatic / sediment

Predicted data and various experimental studies of the test chemical were reviewed for the bioaccumulation end point which are summarized as below:

 

In a prediction done using the BCFBAF Programof Estimation Programs Interface was used to predict the bioconcentration factor (BCF) of test chemical. The bioconcentration factor (BCF) of test chemical was estimated to be 24.13 L/kg whole body w.w (at 25 deg C).

 

Using Bio-concentration Factor module(ACD (Advanced Chemistry Development)/I-Lab predictive module, 2017)),Bio-concentration Factor of the test chemical was estimated to be 1.97, 2.04, 2.72, 9.28, 56.6, 157, 191 and 196 at pH range 1, 2, 3, 4, 5, 6 and 7-14, respectively.

 

Bioconcentration Factor (BCF) of test chemical was estimated using Chemspider database(modelling database, 2017). The bioconcentration factor of test chemical was estimated to be 353.72 at pH 5.5 and 381.57 at pH 7.4, respectively.

 

Another predicted data was estimated using SciFinder database (American Chemical Society (ACS), 2017) for predicting the bioconcentration factor (BCF) of test chemical.The bioconcentration factor (BCF) of test chemical was estimated to be 2.61, 3.49, 11.9, 72.6, 201, 245 and 251 at pH range 1, 2, 3, 4, 5, 6 and 7-10 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 chemical was estimated to be 24.5 dimensionless . The predicted BCF result based on the 5 OECD principles.

 

In a supporting weight of evidence study from authoritative database (2018) for the test chemical,Bioaccumulation experiment was conducted on test organism Cyprinus carpio for 6 weeks for evaluating the bioconcentration factor (BCF value) of test chemical. 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. Test chemical was prepared in HCO-20.Test chemical nominal conc. used for the study was 0.4mg/l and 0.04 mg/l, respectively. Analytical method involve the recovery ratio: Test water:1st concentration area : 95.6 %, 2nd concentration area : 98.8 %, Fish : 73.2 %, - Limit of detection : Fish : 0.091 ppm. Range finding study involve the TLm(48h) ≥ 100 ppm (w/v) on Rice fish (Oryzias latipes).The bioconcentration factor (BCF value) of test substance on Cyprinus carpio was determined to be in the range of 0.26-4.5 L/Kg at a conc. of 0.4 mg/l and ≤ 2.5 L/Kg at a conc. of 0.04 mg/l, respectively.

 

For the test chemical, the bioaccumulation study in fish was conducted for estimating the BCF (bioaccumulation factor) value of test chemical (HSDB and PubChem, 2017). The bioaccumulation factor (BCF) value was calculated using a log Kow of 4.27 and a regression-derived equation. The estimated BCF (bioaccumulation factor) value of test chemical was determined to be 79 dimensionless.

 

On the basis of above results for test chemical (from modelling databases,2017), it can be concluded that the BCF value of test substanceupto 381.57 dimensionless,which does not exceed the bioconcentration threshold of 2000, indicating that the test chemical is not expected to bioaccumulate in the food chain.

Adsorption / desorption

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 (Experimental study report, 2018). The solutions of the test substance and reference substances were prepared in appropriate solvents. A test item solution was prepared by accurately weighing 4 mg of test item and diluted with Acetonitrile up to 10 ml. Thus, the test solution concentration was 400 mg/l. The pH of test substance was 5.1. 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 Acetanilide, 4-chloroaniline, 4-methylaniline(p-Tolouidine), N-methylaniline, p-toluamide, Aniline, 2,5 -Dichloroaniline, 4-nitrophenol, 2 - nitrophenol, 2-nitrobenzamide, 3-nitrobenzamide, Nitrobenzene, 4 -Nitrobenzamide, 1 -naphthylamine, 1 -naphtol, Direct Red 81, Benzoic acid methylester, Carbendazim, Benzoic acid phenylester, Xylene, Ethylbenzene, Toluene, Naphthalene, 1,2,3-trichlorobenzene, Pentachlorophenol, Phenol, N,N-dimethylbenzamide, 3,5 -dinitrobenzamide, N-methylbenzamide, Benzamide, phenanthrene, DDT having Koc value ranging from 1.25 to 5.63.

The Log Koc value of test chemical was determined to be 3.498 ± 0.001 at 25°C. This log Koc value indicates that the test chemical has a strong sorption to soil and sediment and therefore have negligible to slow migration potential to ground water.