Methyl isonicotinate

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:

key study

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

Specific details on test material used for the study:

- Name of test material : Methyl Isonicotinate
- Molecular formula : C7H7NO2
- Molecular weight : 137.1373 g/mol
- Smiles notation : c1(C(=O)OC)ccncc1
- InChl : 1S/C7H7NO2/c1-10-7(9)6-2-4-8-5-3-6/h2-5H,1H3
- Substance type: Organic
- Physical state: Liquid

Oxygen conditions:

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

Inoculum or test system:

other: mixed populations of environmental microorganisms

Duration of test (contact time):

2.822 wk

Based on:

not specified

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

Parameter:

other: Half-life

Value:

50

Sampling time:

2.822 wk

Remarks on result:

other: readily biodegradable as estimated by BIOWIN model

Details on results:

Biowin1 (Linear Model Prediction) : 0.7019 (Biodegrades Fast)
Biowin2 (Non-Linear Model Prediction): 0.9708 (Biodegrades Fast)
Biowin3 (Ultimate Biodegradation Timeframe): 2.8222 (Weeks)
Biowin4 (Primary Biodegradation Timeframe): 3.8601 (Days)
Biowin5 (MITI Linear Model Prediction) : 0.6477 (Biodegrades Fast)
Biowin6 (MITI Non-Linear Model Prediction): 0.7413 (Biodegrades Fast)
Biowin7 (Anaerobic Model Prediction): 1.1877 (Biodegrades Fast)
Ready Biodegradability Prediction: YES

BIOWIN (v4.10) Program Results:

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

SMILES : O=C(OC)c(ccnc1)c1

CHEM : 4-Pyridinecarboxylic acid, methyl ester

MOL FOR: C7 H7 N1 O2

MOL WT : 137.14

--------------------------- 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) : Biodegrades Fast

Biowin6 (MITI Non-Linear Model Prediction): Biodegrades Fast

Biowin7 (Anaerobic Model Prediction): Biodegrades Fast

Ready Biodegradability Prediction: YES

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

TYPE | NUM | Biowin1 FRAGMENT DESCRIPTION | COEFF | VALUE

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

Frag | 1 | Ester [-C(=O)-O-C] | 0.1742 | 0.1742

Frag | 1 | Pyridine ring | -0.1546 | -0.1546

MolWt| * | Molecular Weight Parameter | | -0.0653

Const| * | Equation Constant | | 0.7475

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

RESULT | Biowin1 (Linear Biodeg Probability) | | 0.7019

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

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

TYPE | NUM | Biowin2 FRAGMENT DESCRIPTION | COEFF | VALUE

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

Frag | 1 | Ester [-C(=O)-O-C] | 4.0795 | 4.0795

Frag | 1 | Pyridine ring | -1.6381 | -1.6381

MolWt| * | Molecular Weight Parameter | | -1.9474

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

RESULT | Biowin2 (Non-Linear Biodeg Probability) | | 0.9708

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

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 | 1 | Ester [-C(=O)-O-C] | 0.1402 | 0.1402

Frag | 1 | Pyridine ring | -0.2142 | -0.2142

MolWt| * | Molecular Weight Parameter | | -0.3031

Const| * | Equation Constant | | 3.1992

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

RESULT | Biowin3 (Survey Model - Ultimate Biodeg) | | 2.8222

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

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

TYPE | NUM | Biowin4 FRAGMENT DESCRIPTION | COEFF | VALUE

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

Frag | 1 | Ester [-C(=O)-O-C] | 0.2290 | 0.2290

Frag | 1 | Pyridine ring | -0.0187 | -0.0187

MolWt| * | Molecular Weight Parameter | | -0.1979

Const| * | Equation Constant | | 3.8477

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

RESULT | Biowin4 (Survey Model - Primary Biodeg) | | 3.8601

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

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 | Ester [-C(=O)-O-C] | 0.3437 | 0.3437

Frag | 1 | Pyridine ring | -0.0335 | -0.0335

Frag | 4 | Aromatic-H | 0.0082 | 0.0329

Frag | 1 | Methyl [-CH3] | 0.0004 | 0.0004

MolWt| * | Molecular Weight Parameter | | -0.4080

Const| * | Equation Constant | | 0.7121

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

RESULT | Biowin5 (MITI Linear Biodeg Probability) | | 0.6477

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

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

TYPE | NUM | Biowin6 FRAGMENT DESCRIPTION | COEFF | VALUE

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

Frag | 1 | Ester [-C(=O)-O-C] | 2.4462 | 2.4462

Frag | 1 | Pyridine ring | -0.4599 | -0.4599

Frag | 4 | Aromatic-H | 0.1201 | 0.4806

Frag | 1 | Methyl [-CH3] | 0.0194 | 0.0194

MolWt| * | Molecular Weight Parameter | | -3.9590

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

RESULT |Biowin6 (MITI Non-Linear Biodeg Probability)| | 0.7413

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

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 | 1 | Ester [-C(=O)-O-C] | 0.1719 | 0.1719

Frag | 1 | Pyridine ring | 0.6411 | 0.6411

Frag | 4 | Aromatic-H | -0.0954 | -0.3817

Frag | 1 | Methyl [-CH3] | -0.0796 | -0.0796

Const| * | Equation Constant | | 0.8361

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

RESULT | Biowin7 (Anaerobic Linear Biodeg Prob) | | 1.1877

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

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:

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 Methyl Isonicotinate
is expected to be readily biodegradable.

Executive summary:

Estimation Programs Interface Suite (EPI suite, 2017) was run to predict the biodegradation potential of the test compound Methyl Isonicotinate (CAS no. 2459 -09 -8) 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 the test chemical Methyl Isonicotinate is expected to be readily biodegradable.

Description of key information

Estimation Programs Interface Suite (EPI suite, 2017) was run to predict the biodegradation potential of the test compound Methyl Isonicotinate (CAS no. 2459 -09 -8) 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 the test chemical Methyl Isonicotinate is expected to be readily biodegradable.

Key value for chemical safety assessment

Biodegradation in water:

readily biodegradable

Additional information

Various predicted and experimental data for the target compound Methyl Isonicotinate (CAS No. 2459 -09 -8) and supporting weight of evidence studies for its closest read across substance with logKow as the primary descriptor were reviewed for the biodegradation end point which are summarized as below:

 

In first prediction using the Estimation Programs Interface Suite (EPI suite, 2017) the biodegradation potential of the test compound Methyl Isonicotinate (CAS No. 2459 -09 -8) 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 the test chemical Methyl Isonicotinate is expected to be readily biodegradable.

 

In a supporting study from peer reviewed journal (Biochemical Journal (1972)) for target chemical (2459-09-8) biodegradation experiment was conducted. Biodegradation study was conducted for evaluating the biodegradability of test substance Methyl Isonicotinate. Test was performed on the two strains Strain 4C1 and Strain 4C2 of bacteria able to grow with N methyl-isonicotinate as sole source of carbon and nitrogen. Two pathways by which Nmethylisonicotinate may be oxidized: one as in strain4C1 involving removal of the methyl group and oxidation to formaldehyde before ring-fission, and the other, as in strain 4C2, where ring-fission probably occurs before the liberation of methylamine from the N-methyl group of the aliphatic ring-fission product. Cultures were supplemented with 0.1 g of Oxoid yeast extract/liter. Media were sterilized by autoclaving at 121°C for 20min. starting culture 35 ml was inoculated in 100 ml conical flask and then reinoculated in the larger flask. Culture stored in the proper conditions of temperature and pH. Strain 4C1 was determine to metabolize N-methylisonicotinate most rapidly at 30°C at pH 7-7.2, with a substrate concentration of 200 mg/liter (0.2 g/l). Strain 4C1 was determine to metabolize N-methylisonicotinate most rapidly whereas Strain 4C2 were oxidized without lag, with oxygen uptakes of 4.5 mol/mol. Based on the oxygen uptake and oxidation of N Methylisonicotinate by the Strain 4C1 and Strain 4C2, it was concluded that the chemical was biodegradable.

 

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 Methyl isonicotinate (2459-09-8) was estimated. Test was carried out on the aerobic mcroorganisms. Test substance undergoes 85.1666 % degradation by BOD in 28 days. Thus, based on percentage degradation, the test chemical Methyl Isonicotinate was estimated to be readily biodegradable in water.

Similarly another biodegradation study (from authoritative database J-CHECK, 2017) was conducted for 28 days for evaluating the percentage biodegradability of test substance 2 -benzofuran-1(3H)-one (CAS no. 87 -41 -2). 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 95, 96 and 100% by BOD, TOC removal and HPLC parameter in 28 days. Thus, based on percentage degradation, 2 -benzofuran-1(3H)-one is considered to be readily biodegradable in nature.

 

Similarly another biodegradation study (from authoritative database J-CHECK, 2017) was conducted for evaluating the percentage biodegradability of test substance 1,4-Benzenedicarboxylicacid, 1,4-dimethyl ester. 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 84% and 100% by BOD and HPLC parameter in 14 days. Thus, based on percentage degradation of 1,4- Benzenedicarboxylic acid, 1,4-dimethyl ester is considered to be readily biodegradable in water.

 

On the basis of above results for target chemical Methyl Isonicotinate (CAS No. 2459 -09 -8) from J- check, EPI suite, QSAR, 2017 and Biochemical Journal 1972 and for its read across substance (from authoritative database J-CHECK, it can be concluded that the test substance Methyl Isonicotinate can be expected to be readily biodegradable in nature.