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

Toxicity to aquatic algae and cyanobacteria

Link to relevant study record(s)

Reference

Endpoint:

toxicity to aquatic algae and cyanobacteria

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:

Data is from OECD QSAR toolbox version 3.4 and the QMRF report has been attached.

Qualifier:

according to guideline

Guideline:

other: Estimated data

Principles of method if other than guideline:

Method: other: Toxicity Test acc. to OECD guidelines

GLP compliance:

not specified

Specific details on test material used for the study:

- IUPAC Name: 2-Chloro-6,7-dimethoxyquinazolin-4-amine
- Mol. formula: C10H10ClN3O2
- Molecular Weight: 239.661 g/mole
- Smiles: n1c(c2cc(OC)c(cc2nc1Cl)OC)N
- InChI: 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)

Analytical monitoring:

not specified

Details on sampling:

No data available

Vehicle:

not specified

Details on test solutions:

No data available

Test organisms (species):

Desmodesmus subspicatus (previous name: Scenedesmus subspicatus)

Details on test organisms:

- Common name: Green algae

Test type:

static

Water media type:

freshwater

Total exposure duration:

72 h

Post exposure observation period:

No data available

Hardness:

No data available

Test temperature:

No data available

pH:

No data available

Dissolved oxygen:

No data available

Salinity:

No data available

Conductivity:

No data available

Nominal and measured concentrations:

Estimated data

Details on test conditions:

No data available

Reference substance (positive control):

not specified

Key result

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

119.857 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

growth rate

Remarks on result:

other: Nontoxic

Details on results:

No data available

Results with reference substance (positive control):

No data available

Reported statistics and error estimates:

No data available

The prediction was based on dataset comprised from the following descriptors: EC50
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

((((((((((((((("a" or "b" or "c" or "d" )  and "e" )  and ("f" and ( not "g") )  )  and ("h" and ( not "i") )  )  and ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and ("n" and ( not "o") )  )  and ("p" and ( not "q") )  )  and ("r" and ( not "s") )  )  and ("t" and ( not "u") )  )  and ("v" and ( not "w") )  )  and ("x" and ( not "y") )  )  and "z" )  and ("aa" and ( not "ab") )  )  and ("ac" and "ad" )  )

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 Class 2 (less inert compounds) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Alkoxy AND Aromatic heterocyclic halide AND Aryl halide AND Ether AND Overlapping groups AND Quinazoline by Organic Functional groups (nested)

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Alkyl arenes by Organic Functional groups (nested)

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Alkoxy AND Aromatic heterocyclic halide AND Aryl AND Aryl halide AND Ether AND Fused heterocyclic aromatic AND Pyrimidine AND Quinazoline by Organic Functional groups

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Precursors quinoid compounds by Organic Functional groups

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Alkoxy AND Aromatic heterocyclic halide AND Aryl AND Aryl halide AND Ether AND Fused heterocyclic aromatic AND Pyrimidine AND Quinazoline by Organic Functional groups

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Alkyl halide by Organic Functional groups

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Alkoxy AND Aromatic heterocyclic halide AND Aryl AND Aryl halide AND Ether AND Fused heterocyclic aromatic AND Pyrimidine AND Quinazoline by Organic Functional groups

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Aromatic amine by Organic Functional groups

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Alkoxy AND Aromatic heterocyclic halide AND Aryl AND Aryl halide AND Ether AND Fused heterocyclic aromatic AND Pyrimidine AND Quinazoline by Organic Functional groups

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Dianilines by Organic Functional groups

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Alkoxy AND Aromatic heterocyclic halide AND Aryl AND Aryl halide AND Ether AND Fused heterocyclic aromatic AND Pyrimidine AND Quinazoline by Organic Functional groups

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Carbohydrate/ Monosaccharide by Organic Functional groups

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Alkoxy AND Aromatic heterocyclic halide AND Aryl AND Aryl halide AND Ether AND Fused heterocyclic aromatic AND Pyrimidine AND Quinazoline by Organic Functional groups

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Azo by Organic Functional groups

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Alkoxy AND Aromatic heterocyclic halide AND Aryl AND Aryl halide AND Ether AND Fused heterocyclic aromatic AND Pyrimidine AND Quinazoline by Organic Functional groups

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Fused carbocyclic aromatic by Organic Functional groups

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Alkoxy AND Aromatic heterocyclic halide AND Aryl AND Aryl halide AND Ether AND Fused heterocyclic aromatic AND Pyrimidine AND Quinazoline by Organic Functional groups

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Sulfide OR Sulfonic acid by Organic Functional groups

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aromatic Carbon [C] AND Aromatic Nitrogen AND Chlorine, aromatic attach [-Cl] AND Chlorine, olefinic attach [-Cl] AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] by Organic functional groups (US EPA)

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Fluorine, aromatic attach [-F] by Organic functional groups (US EPA)

Domain logical expression index: "z"

Similarity boundary:Target: COc1cc2c(cc1OC)c(N)nc(Cl)n2
Threshold=40%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "aa"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O AND Group 17 - Halogens Cl AND Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "ab"

Referential boundary: The target chemical should be classified as Group 17 - Halogens I by Chemical elements

Domain logical expression index: "ac"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.08

Domain logical expression index: "ad"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.8

Validity criteria fulfilled:

not specified

Conclusions:

The EC50 value was estimated to be 119.856 mg/l when 2-Chloro-6,7-dimethoxyquinazolin-4-amine exposed to Desmodesmus subspicatus for 72hrs.

Executive summary:

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, toxicity on Desmodesmus subspicatus (previous name: Scenedesmus subspicatus) was predicted for 2-Chloro-6,7-dimethoxyquinazolin-4-amine (23680-84-4).The EC50 value was estimated to be 119.856 mg/l when 2-Chloro-6,7-dimethoxyquinazolin-4-amine exposed to Desmodesmus subspicatus for 72hrs.

Description of key information

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, toxicity on Desmodesmus subspicatus (previous name: Scenedesmus subspicatus) was predicted for 2-Chloro-6,7-dimethoxyquinazolin-4-amine (23680-84-4).The EC50 value was estimated to be 119.856 mg/l when 2-Chloro-6,7-dimethoxyquinazolin-4-amine exposed to Desmodesmus subspicatus for 72hrs.

Key value for chemical safety assessment

EC50 for freshwater algae:

119.856 mg/L

Additional information

Based on the various experimental data and prediction data for the target chemical as well as RA chemical which was selected on the basis of structure similarity study have been reviewed to determine the toxic nature of 2-Chloro-6,7-dimethoxyquinazolin-4-amine (23680-84-4) on the growth of algae. The studies are as mentioned below:  

In the first predicted weight of evidence report for the 2-Chloro-6,7-dimethoxyquinazolin-4-amine (23680-84-4) from SSS (QSAR, 2017) toxicity study was carried out. Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, toxicity on Desmodesmus subspicatus (previous name: Scenedesmus subspicatus) was predicted for 2-Chloro-6,7-dimethoxyquinazolin-4-amine (23680-84-4).The EC50 value was estimated to be 119.856 mg/l when 2-Chloro-6,7-dimethoxyquinazolin-4-amine exposed to Desmodesmus subspicatus for 72hrs.

 

Similarly in the second prediction study was performed based on the prediction done using the EPI Suite ECOSAR version 1.10, the short term toxicity on green algae was predicted for test substance 2-chloro-6,7-dimethoxyquinazolin- 4-amine (23680 -84 -4). On the basis of effects observed in a static freshwater system, the effect concentration EC50 value for the substance 2-chloro-6,7-dimethoxyquinazolin-4- amine is estimated to be 185.347 mg/l for green algae for 96 hrs duration. Based on this value, it can be concluded that the test chemical 2-chloro-6,7-dimethoxyquinazolin-4-amine can be considered as non-toxic to green algae at environmentally relevant concentrations and can be considered not-classified as toxic as per the CLP classification criteria.

 

Similarly in the third weight of evidence study for the read across Aminobenzene (62-53-3) (From j-check, 2017) Determination of short-term toxicity of chemical Aminobenzene on aquatic green algae. Test was performed in the static system. After the exposure of chemical effect concentration was measured at which 50% growth inhibited by chemical. Based on the growth inhibition of green algae, the EC50 was 110 mg/l and the NOEC was 3.7 mg/l. based on the biomass and area under the growth curve, the EC50 was 41 mg/l and the NOEC was 11 mg/l. Thus based on the EC50 (110 mg/l) chemical Aminobenzene (Aniline) consider as nontoxic and cannot be classified as per the CLP classification criteria.

 

Similarly in the fourth weight of evidence study for the RA chemical (738 -70 -5), chemosphere, 2014. Determination of short term toxicity of chemical 2,4-Diamino-5-(3,4,5-trimethoxybenzyl)- pyrimidin (Trimethoprim) on the growth of aquatic algae Pseudokirchneriella subcapitata CCAP 278/4 for 72hrs. Green algae were cultivated and tested in the OECD TG 201 medium and in the growth medium BG 11. Test performed in 250 ml Erlenmeyer flasks filled with 100 mL of the test medium. 3 replicates were used in the test. After the exposure of chemical for 72hrs, the ErC10 was 65 mg/l with the 95% CI of 0.01-103 mg/l and the ErC50 was 129 mg/l with 95% CI 123-136 mg/l. Based on the growth inhibition of Selenastrum capricornutum CCAP 278/4, due to the exposure of chemical, the ErC50 was 129 mg/l with 95% CI 123-136 mg/l. Based on the ErC50, it is concluded that the chemical was nontoxic and can be consider to be not classified as toxic to aquatic environment as per the CLP classification criteria.

Thus based on the above data sources for target chemical 2-Chloro-6,7-dimethoxyquinazolin-4-amine (23680-84-4) from various experimental studies and predicted studies from QSAR, EPIsuite, j-check it was summarized that the chemical was nontoxic and can be consider to be not classified as toxic as per the CLP classification criteria.