2-chloro-6,7-dimethoxyquinazolin-4-amine

Biodegradation in water: screening tests

Link to relevant study record(s)

Reference

Endpoint:

biodegradation in water: screening tests

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

The supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

OECD Guideline 301 C (Ready Biodegradability: Modified MITI Test (I))

Principles of method if other than guideline:

The data is predicted using the OECD QSAR toolbox version 3.4 with logKow as the primary descriptor.

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material : 2-chloro-6,7-dimethoxyquinazolin-4-amine
- Molecular formula : C10H10ClN3O2
- Molecular weight : 239.661 g/mol
- Smiles notation : n1c(c2cc(OC)c(cc2nc1Cl)OC)N
- InChl : 1S/C10H10ClN3O2/c1-15-7-3-5-6(4-8(7)16-2)13-10(11)14-9(5)12/h3-4H,1-2H3,(H2,12,13,14)
- Substance type: Organic
- Physical state: Solid

Oxygen conditions:

aerobic

Inoculum or test system:

other: Microorganisms

Duration of test (contact time):

28 d

Based on:

not specified

Parameter followed for biodegradation estimation:

other: BOD

Key result

Parameter:

other: BOD

Value:

0.333

Sampling time:

28 d

Remarks on result:

other: Other details not known

Details on results:

Test substance undergoes 0.33% degradation by BOD in 28 days.

The prediction was based on dataset comprised from the following descriptors: BOD
Estimation method: Takes average value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((("a" or "b" or "c" or "d" )  and "e" )  and "f" )  and "g" )  and ("h" and ( not "i") )  )  and "j" )  and ("k" and ( not "l") )  )  and ("m" and "n" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Non-covalent interaction AND Non-covalent interaction >> DNA intercalation AND Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines AND Radical AND Radical >> Radical mechanism via ROS formation (indirect) AND Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines AND SN1 AND SN1 >> Nucleophilic attack after metabolic nitrenium ion formation AND SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines by DNA binding by OASIS v.1.4

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as AN2 AND AN2 >> Nucleophilic addition to pyridonimine tautomer of aminopyridoindoles or aminopyridoimidazoles (hypothesized) AND AN2 >> Nucleophilic addition to pyridonimine tautomer of aminopyridoindoles or aminopyridoimidazoles (hypothesized) >> Heterocyclic Aromatic Amines AND Radical reactions AND Radical reactions >> ROS generation and direct attack of hydroxyl radical to the C8 position of nucleoside base AND Radical reactions >> ROS generation and direct attack of hydroxyl radical to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines AND SE reaction (CYP450-activated heterocyclic amines) AND SE reaction (CYP450-activated heterocyclic amines) >> Direct attack of arylnitrenium cation to the C8 position of nucleoside base  AND SE reaction (CYP450-activated heterocyclic amines) >> Direct attack of arylnitrenium cation to the C8 position of nucleoside base  >> Heterocyclic Aromatic Amines AND SNAr AND SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds AND SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds >> Activated aryl and heteroaryl compounds AND SR reaction (peroxidase-activated heterocyclic amines) AND SR reaction (peroxidase-activated heterocyclic amines) >> Direct attack of arylnitrenium radical to the C8 position of nucleoside base AND SR reaction (peroxidase-activated heterocyclic amines) >> Direct attack of arylnitrenium radical to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines by Protein binding by OASIS v1.4

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as SNAr AND SNAr >> Nucleophilic aromatic substitution AND SNAr >> Nucleophilic aromatic substitution >> Halo-pyrimidines by Protein binding by OECD

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Anilines (Unhindered) by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as days - weeks by Biodeg primary (Biowin 4) ONLY

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Does NOT Biodegrade Fast by Biodeg probability (Biowin 1) ONLY

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Does NOT Biodegrade Fast by Biodeg probability (Biowin 7) ONLY

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Basic [0,10) AND No pKa value by Ionization at pH = 7.4

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Acidic [0,10) OR Acidic [90,100] OR Basic [10,20) by Ionization at pH = 7.4

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Very fast by Bioaccumulation - metabolism half-lives ONLY

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Aromatic amine   [-NH2  or  -NH-] AND Aromatic chloride   [-CL] AND Aromatic ether  [-O-aromatic carbon] AND Aromatic-H AND Methyl  [-CH3] by Biodegradation fragments (BioWIN MITI)

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Aromatic nitro  [-NO2] OR Aromatic-CH2 OR Aromatic-CH3 OR -C=CH  [alkenyl hydrogen] OR Ketone   [-C-C(=O)-C-] OR Quaternary amine OR Triazine ring (symmetric) by Biodegradation fragments (BioWIN MITI)

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of Molecular weight which is >= 100 Da

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of Molecular weight which is <= 248 Da

Validity criteria fulfilled:

not specified

Interpretation of results:

not readily biodegradable

Conclusions:

The test chemical 2-Chloro-6,7-dimethoxyquinazolin-4-amine was estimated to be not readily biodegradable in water.

Executive summary:

Biodegradability of 2-Chloro-6,7-dimethoxyquinazolin-4-amine (CAS no. 23680 -64 -4) is predicted using QSAR toolbox version 3.4 with logKow as the primary descriptor. Test substance undergoes 0.33% degradation by BOD in 28 days. Thus, based on percentage degradation, the test chemical 2-Chloro-6,7-dimethoxyquinazolin-4-amine was estimated to be not readily biodegradable in water.

Description of key information

Biodegradability of 2-Chloro-6,7-dimethoxyquinazolin-4-amine (CAS no. 23680 -64 -4) is predicted using QSAR toolbox version 3.4 (2017) with logKow as the primary descriptor. Test substance undergoes 0.33% degradation by BOD in 28 days. Thus, based on percentage degradation, the test chemical 2-Chloro-6,7-dimethoxyquinazolin-4-amine was estimated to be not readily biodegradable in water.

Key value for chemical safety assessment

Biodegradation in water:

under test conditions no biodegradation observed

Additional information

Various predicted data for the target compound 2-Chloro-6,7-dimethoxyquinazolin-4-amine (CAS No. 23680-84-4) 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 a prediction done by SSS (2017) using OECD QSAR toolbox version 3.4 with logKow as the primary descriptor, percentage biodegradability of test chemical2-Chloro-6,7-dimethoxyquinazolin-4-amine(CAS No. 23680-84-4) was estimated.Test substance undergoes 0.33% degradation by BOD in 28 days. Thus, based on percentage degradation, the test chemical 2-Chloro-6,7-dimethoxyquinazolin-4-amine was estimated to be not readily biodegradable in water.

 

In another prediction using the Estimation Programs Interface Suite (EPI suite, 2017), the biodegradation potential of the test compound2-Chloro-6,7-dimethoxyquinazolin-4-amine(CAS No. 23680-84-4) 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 2-Chloro-6,7-dimethoxyquinazolin-4-amine is expected to be not readily biodegradable.

 

In a supporting weight of evidence study from authoritative database (J-CHECK, HSDB, SRC PhysProp database, 2017 and EnviChem, 2014) for the read across chemical 1,5-Diaminonaphthalene (CAS no. 2243-62-1),biodegradation experiment was conducted for 28 days for evaluating the percentage biodegradability of test substance1,5-Diaminonaphthalene (CAS no. 2243-62-1). The study was performed according to OECD Guideline 301 C (Ready Biodegradability: Modified MITI Test (I) or OECD Guideline 302 C (Inherent Biodegradability: Modified MITI Test (II)) under aerobic conditions at a temperature of 25°C and pH 7.0.Activated sludge 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 substance 1,5-Diaminonaphthalene was determined to be 0 and 3% degradation by BOD and HPLC parameter in 28 days. Thus, based on percentage degradation, 1,5-Diaminonaphthalene is considered to be not readily biodegradable in nature.

 

Another biodegradation studywas conducted for 28 days for evaluating the percentage biodegradability of read across substance 1,8-Diaminonaphthalene (CAS no. 479-27-6)(J-CHECK, SRC PhysProp database, 2017 and EnviChem, 2014). The study was performed according to OECD Guideline 301 C (Ready Biodegradability: Modified MITI Test (I) or OECD Guideline 302 C (Inherent Biodegradability: Modified MITI Test (II)) under aerobic conditions at a temperature of 25°C and pH 7.0.Activated sludge 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 substance1,8-Diaminonaphthalenewas determined to be 0, 9 and 1% by BOD, TOC removal and HPLC parameter in 28 days. Thus, based on percentage degradation,1,8-Diaminonaphthalene is considered to be not readily biodegradable in nature.

 

For the read across chemical 3,3'-Sulfonyldianiline (CAS no. 599-61-1) from authoritative database (J-CHECK, 2017),biodegradation study was conducted for 28 days for evaluating the percentage biodegradability of read across substance 3,3'-Sulfonyldianiline. Activated sludge 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 substance 3,3'-Sulfonyldianiline was determined to be 0 and 1% by BOD, TOC removal and HPLC parameter in 28 days. Thus, based on percentage degradation, 3,3'-Sulfonyldianiline is considered to be not readily biodegradable in nature.

 

On the basis of above results for target chemical 2-Chloro-6,7-dimethoxyquinazolin-4-amine(from OECD QSAR toolbox version 3.4 and EPI suite, 2017) and for its read across substance (from authoritative database J-CHECK, HSDB, SRC PhysProp database & EnviChem), it can be concluded that the test substance 2 -Chloro-6,7 -dimethoxyquinazolin-4 -amine can be expected to be not readily biodegradable in nature.