2-butyl-6-(butylamino)-1H-benz[de]isoquinoline-1,3(2H)-dione

Biodegradation in water: screening tests

Link to relevant study record(s)

Reference

Endpoint:

biodegradation in water: ready biodegradability

Type of information:

calculation (if not (Q)SAR)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Justification for type of information:

Data is from computational model developed by USEPA

Qualifier:

according to guideline

Guideline:

other: Modeling database

Principles of method if other than guideline:

The Biodegradation Probability Program (BIOWIN) estimates the probability for the rapid aerobic biodegradation of an organic chemical in the presence of mixed populations of environmental microorganisms .The model is part of the EpiSuite program of the US-EPA. Estimations are made with BIOWIN version 4.10. Estimates are based upon fragment constants that were developed using multiple linear and non-linear regression analyses. Experimental biodegradation data for the multiple linear and non-linear regressions were obtained from Syracuse Research Corporation's (SRC) data base of evaluated biodegradation data (Howard et. al., 1987). This version (v4.10) designates the models as follows (see also Boethling et al. 2003):
Biowin1 = linear probability model
Biowin2 = nonlinear probability model
Biowin3 = expert survey ultimate biodegradation model
Biowin4 = expert survey primary biodegradation model
Biowin5 = MITI linear model
Biowin6 = MITI nonlinear model
Biowin7 = anaerobic biodegradation model

GLP compliance:

not specified

Oxygen conditions:

other: aerobic (Biowin 1-6) and anaerobic (Biowin 7)

Inoculum or test system:

other: mixed populations of environmental microorganisms

Details on study design:

Using the computer tool BIOWIN v4.10 by US-EPA (EPIWIN) the aerobic as well as the anaerobic biodegradability of the test material can be estimated. The follwoing seven different models are used by the tool: Linear Model, Non-Linear Model, Ultimate Biodegradation Timeframe, Primary Biodegradation Timeframe, MITI LInear Model, MITI Non-Linear Model and Anaerobic Model (calles Biowin 1-7, respectively). Due to this results the overall prediction of readily biodegradability is done for the desired chemical.

Biowin 1 and 2, are intended to convey a general indication of biodegradability under aerobic conditions, and not for any particular medium.
Biowin 1 (Linear model)
The fast biodegradation probability for any compound is calculated by summing, for all the fragments present in that compound, the fragment coefficient multiplied by the number of instances of the fragment in the compound (for MW, the value of that parameter is multiplied by its coefficient), and then adding this summation to the equation constant which is 0.7475. The summed values for each fragment coefficient multiplied by the number of instances appear in the "VALUE" column of the linear results screen.

Biowin 2 (Non-linear model)
Calculation of the fast biodegradation probability for any compound begins by summing, for all the fragments present in that compound, the fragment coefficient multiplied by the number of instances of the fragment in the compound (for MW, the value of that parameter is multiplied by its coefficient), then adding this summation to the equation constant which is 3.0087. The summed values for each fragment coefficient multiplied by the number of instances appear in the "VALUE" column of the non-linear results screen. The non-linear fast biodegradation probability is then calculated from the logistic equation as follows, where total = 3.0087 + the summation as described above:

Biowin 3 and 4 yield estimates for the time required to achieve complete ultimate and primary biodegradation in a typical or "evaluative" aquatic environment.

Biowin 5 and 6 are predictive models for assessing a compound’s biodegradability in the Japanese MITI (Ministry of International Trade and Industry) ready biodegradation test; i.e. OECD 301C. These models use an approach similar to that used to develop Biowin1 and 2. This protocol for determining ready biodegradability is among six officially approved as ready biodegradability test guidelines of the OECD (Organization for Economic Cooperation and Development). A total dataset of 884 chemicals was compiled to derive the fragment probability values that are applied in this MITI Biodegradability method. The dataset consists of 385 chemical that were critically evaluated as "readily degradable" and 499 chemicals that were critically evaluated as "not readily biodegradable".

Biowin 7, the anaerobic biodegradation model, is the most recent. As for the other Biowin models, multiple (linear) regression against molecular fragments was used to develop the model, which predicts probability of rapid degradation in the "serum bottle" anaerobic biodegradation screening test. This endpoint is assumed to be predictive of degradation in a typical anaerobic digester. Biowin7 estimates the probability of fast biodegradation under methanogenic anaerobic conditions; specifically, under the conditions of the "serum bottle" anaerobic biodegradation screening test (Meylan et al. 2007). A total of 169 compounds with serum bottle test data were identified for use in model development.

Out of seven different Biowin models, Biowin model 3 and 4 will help in estimating biodgeradability of the test chemical which was described as below-

Ultimate Biodegradation Timeframe and Primary Biodegradation Timeframe (Biowin 3 and 4)
These two models estimate the time required for "complete" ultimate and primary biodegradation.  Primary biodegradation is the transformation of a parent compound to an initial metabolite.  Ultimate biodegradation is the transformation of a parent compound to carbon dioxide and water, mineral oxides of any other elements present in the test compound, and new cell material. Then the rating was given to each model, which indicates the time required to achieve ultimate and primary biodegradation in a typical or "evaluative" aquatic environment. The ratings for each compound were averaged to obtain a single value for modeling.  The ultimate or primary rating of a compound is calculated by summing, for all the fragments present in that compound.

Key result

Remarks on result:

other: not readily biodegradable as estimated by BIOWIN model

Details on results:

Biowin1 (Linear Model Prediction) : 0.5762: Biodegrades Fast
Biowin2 (Non-Linear Model Prediction): 0.5454: Biodegrades Fast
Biowin3 (Ultimate Biodegradation Timeframe): 2.9440: Weeks
Biowin4 (Primary Biodegradation Timeframe): 3.8094: Days
Biowin5 (MITI Linear Model Prediction) : -0.0723: Does Not Biodegrade Fast
Biowin6 (MITI Non-Linear Model Prediction): 0.0078: Does Not Biodegrade Fast
Biowin7 (Anaerobic Model Prediction): -0.5575: Does Not Biodegrade Fast
Ready Biodegradability Prediction: NO

BIOWIN (v4.10) Program Results:

==============================

SMILES : O=C1N(C(=O)c2c3c(c(NCCCC)ccc13)ccc2)CCCC

CHEM :

MOL FOR: C20 H24 N2 O2

MOL WT : 324.43

--------------------------- BIOWIN v4.10 Results ----------------------------

Biowin1 (Linear Model Prediction) : Biodegrades Fast

Biowin2 (Non-Linear Model Prediction): Biodegrades Fast

Biowin3 (Ultimate Biodegradation Timeframe): Weeks

Biowin4 (Primary Biodegradation Timeframe): Days

Biowin5 (MITI Linear Model Prediction) : Does Not Biodegrade Fast

Biowin6 (MITI Non-Linear Model Prediction): Does Not Biodegrade Fast

Biowin7 (Anaerobic Model Prediction): Does Not Biodegrade Fast

Ready Biodegradability Prediction: NO

------+-----+--------------------------------------------+---------+---------

TYPE | NUM | Biowin1 FRAGMENT DESCRIPTION | COEFF | VALUE

------+-----+--------------------------------------------+---------+---------

Frag | 2 | Linear C4 terminal chain [CCC-CH3] | 0.1084 | 0.2169

Frag | 1 | Aromatic amine [-NH2 or -NH-] | -0.2338 | -0.2338

MolWt| * | Molecular Weight Parameter | | -0.1545

Const| * | Equation Constant | | 0.7475

============+============================================+=========+=========

RESULT | Biowin1 (Linear Biodeg Probability) | | 0.5762

============+============================================+=========+=========

------+-----+--------------------------------------------+---------+---------

TYPE | NUM | Biowin2 FRAGMENT DESCRIPTION | COEFF | VALUE

------+-----+--------------------------------------------+---------+---------

Frag | 2 | Linear C4 terminal chain [CCC-CH3] | 1.8437 | 3.6874

Frag | 1 | Aromatic amine [-NH2 or -NH-] | -1.9070 | -1.9070

MolWt| * | Molecular Weight Parameter | | -4.6069

============+============================================+=========+=========

RESULT | Biowin2 (Non-Linear Biodeg Probability) | | 0.5454

============+============================================+=========+=========

A Probability Greater Than or Equal to 0.5 indicates --> Biodegrades Fast

A Probability Less Than 0.5 indicates --> Does NOT Biodegrade Fast

------+-----+--------------------------------------------+---------+---------

TYPE | NUM | Biowin3 FRAGMENT DESCRIPTION | COEFF | VALUE

------+-----+--------------------------------------------+---------+---------

Frag | 2 | Linear C4 terminal chain [CCC-CH3] | 0.2983 | 0.5967

Frag | 1 | Aromatic amine [-NH2 or -NH-] | -0.1349 | -0.1349

MolWt| * | Molecular Weight Parameter | | -0.7169

Const| * | Equation Constant | | 3.1992

============+============================================+=========+=========

RESULT | Biowin3 (Survey Model - Ultimate Biodeg) | | 2.9440

============+============================================+=========+=========

------+-----+--------------------------------------------+---------+---------

TYPE | NUM | Biowin4 FRAGMENT DESCRIPTION | COEFF | VALUE

------+-----+--------------------------------------------+---------+---------

Frag | 2 | Linear C4 terminal chain [CCC-CH3] | 0.2691 | 0.5381

Frag | 1 | Aromatic amine [-NH2 or -NH-] | -0.1084 | -0.1084

MolWt| * | Molecular Weight Parameter | | -0.4681

Const| * | Equation Constant | | 3.8477

============+============================================+=========+=========

RESULT | Biowin4 (Survey Model - Primary Biodeg) | | 3.8094

============+============================================+=========+=========

Result Classification: 5.00 -> hours 4.00 -> days 3.00 -> weeks

(Primary & Ultimate) 2.00 -> months 1.00 -> longer

------+-----+--------------------------------------------+---------+---------

TYPE | NUM | Biowin5 FRAGMENT DESCRIPTION | COEFF | VALUE

------+-----+--------------------------------------------+---------+---------

Frag | 1 | Aromatic amine [-NH2 or -NH-] | -0.1577 | -0.1577

Frag | 5 | Aromatic-H | 0.0082 | 0.0411

Frag | 2 | Methyl [-CH3] | 0.0004 | 0.0008

Frag | 6 | -CH2- [linear] | 0.0494 | 0.2965

MolWt| * | Molecular Weight Parameter | | -0.9652

Const| * | Equation Constant | | 0.7121

============+============================================+=========+=========

RESULT | Biowin5 (MITI Linear Biodeg Probability) | | -0.0723

============+============================================+=========+=========

------+-----+--------------------------------------------+---------+---------

TYPE | NUM | Biowin6 FRAGMENT DESCRIPTION | COEFF | VALUE

------+-----+--------------------------------------------+---------+---------

Frag | 1 | Aromatic amine [-NH2 or -NH-] | -1.2264 | -1.2264

Frag | 5 | Aromatic-H | 0.1201 | 0.6007

Frag | 2 | Methyl [-CH3] | 0.0194 | 0.0389

Frag | 6 | -CH2- [linear] | 0.4295 | 2.5770

MolWt| * | Molecular Weight Parameter | | -9.3658

============+============================================+=========+=========

RESULT |Biowin6 (MITI Non-Linear Biodeg Probability)| | 0.0078

============+============================================+=========+=========

A Probability Greater Than or Equal to 0.5 indicates --> Readily Degradable

A Probability Less Than 0.5 indicates --> NOT Readily Degradable

------+-----+--------------------------------------------+---------+---------

TYPE | NUM | Biowin7 FRAGMENT DESCRIPTION | COEFF | VALUE

------+-----+--------------------------------------------+---------+---------

Frag | 2 | Linear C4 terminal chain [CCC-CH3] | -0.3177 | -0.6355

Frag | 1 | Aromatic amine [-NH2 or -NH-] | -0.2778 | -0.2778

Frag | 5 | Aromatic-H | -0.0954 | -0.4772

Frag | 2 | Methyl [-CH3] | -0.0796 | -0.1591

Frag | 6 | -CH2- [linear] | 0.0260 | 0.1559

Const| * | Equation Constant | | 0.8361

============+============================================+=========+=========

RESULT | Biowin7 (Anaerobic Linear Biodeg Prob) | | -0.5575

============+============================================+=========+=========

A Probability Greater Than or Equal to 0.5 indicates --> Biodegrades Fast

A Probability Less Than 0.5 indicates --> Does NOT Biodegrade Fast

Ready Biodegradability Prediction: (YES or NO)

----------------------------------------------

Criteria for the YES or NO prediction: If the Biowin3 (ultimate survey

model) result is "weeks" or faster (i.e. "days", "days to weeks", or

"weeks" AND the Biowin5 (MITI linear model) probability is >= 0.5, then

the prediction is YES (readily biodegradable). If this condition is not

satisfied, the prediction is NO (not readily biodegradable). This method

is based on application of Bayesian analysis to ready biodegradation data

(see Help). Biowin5 and 6 also predict ready biodegradability, but for

degradation in the OECD301C test only; using data from the Chemicals

Evaluation and Research Institute Japan (CERIJ) database.

Validity criteria fulfilled:

not specified

Interpretation of results:

not readily biodegradable

Conclusions:

The biodegradability of the substance was calculated using seven different Biowin 1-7 models of the BIOWIN v4.10 software. The results indicate that the test chemical 2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione is expected to be not readily biodegradable.

Executive summary:

Estimation Programs Interface Suite (EPI suite, 2017) was run to predict the biodegradation potential of the test compound  2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione (CAS no. 19125 -99 -6) 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  2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione is expected to be not readily biodegradable.

Description of key information

The biodegradability of the substance was calculated using seven different Biowin 1-7 models of the BIOWIN v4.10 software. The results indicate that the test chemical 2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione is expected to be not readily biodegradable.

Key value for chemical safety assessment

Biodegradation in water:

under test conditions no biodegradation observed

Additional information

Predicted data for the substance 2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione and the experimental data of its read across substances were reviewed for the endpoint Biodegradation in water and are summarized below as weight of evidence approach:

Estimation Programs Interface Suite (EPI suite, 2017) was run to predict the biodegradation potential of the test compound  2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione (CAS no. 19125 -99 -6) 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 2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione is expected to be not readily biodegradable.

The biodegradation of 2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione was estimated using QSAR prediction models. Prediction was done using QSAR Toolbox version 3.4. According to the quantitative structure activity relationship(QSAR) model prediction, the substance 2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione shows 6.80% degradation in 28 days. Thus it was concluded that the test compound is not readily biodegradable in water.

28 days test was carried out for the read across substance 5,5-diphenylimidazolidine-2,4-dione [synonym:phenytoin; CAS No. 57-41-0] to determine its biodegradability in water (J-check database, 2017). The concentration of the substance used was 100 mg/L and the concentration of sludge was 30 mg/L. After 28 days 1% degradation was found following BOD parameter while 2% degradation was found following HPLC parameter. These values indicates that the substance 5,5-diphenylimidazolidine-2,4-dione [synonym:phenytoin] is not readily biodegradable in water.

14 days test was carried out for other structurally similar substance N,N'-(3,3'-dimethylbiphenyl-4,4'-ylene)di(acetoacetamide); CAS No. 91-96-3; to determine its biodegradability in water (Finnish Environment database, 2017). The concentration of the substance used was 100 mg/L and the concentration of sludge was 30 mg/L. After 14 days 0% degradation was found following BOD parameter. This value indicates that the substance N,N'-(3,3'-dimethylbiphenyl-4,4'-ylene)di(acetoacetamide) is not readily biodegradable in water.

Considering above results and by applying weight of evidence approach it can be concluded that the substance 2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione is expected to be not readily biodegradable.