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

Short-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Endpoint:

short-term toxicity to aquatic invertebrates

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:

Prediction was done using the OECD QSAR toolbox version 3.4.

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)
- Physical state: Solid

Analytical monitoring:

not specified

Vehicle:

not specified

Test organisms (species):

Daphnia magna

Details on test organisms:

- Common name: Water flea

Test type:

static

Water media type:

freshwater

Total exposure duration:

48 h

Remarks on exposure duration:

No data available

Hardness:

No data available

Test temperature:

19.9 - 20.6 °C

pH:

6.2 - 7.6

Dissolved oxygen:

8.6 - 8.7 mg/L

Nominal and measured concentrations:

Estimated data

Details on test conditions:

No data available

Reference substance (positive control):

not specified

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

151.435 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

other: Intoxication

Remarks on result:

other: Other details not known

Details on results:

After the exposure of chemical, the EC50 was 151.434 mg/l.

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 "w" )  )

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 Reactive unspecified by Acute aquatic toxicity MOA by OASIS ONLY

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Aliphatic Amines by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Carbamate Esters OR Esters by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "j"

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

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Hydrazines OR Inorganic Compound by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "l"

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

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Phenols OR Pyrazoles/Pyrroles by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Salt by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "p"

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: "q"

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

Domain logical expression index: "r"

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: "s"

Referential boundary: The target chemical should be classified as Group 15 - Metalloids As,Sb OR Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "t"

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: "u"

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

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.718

Domain logical expression index: "w"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.43

Validity criteria fulfilled:

not specified

Conclusions:

The EC50 value was estimated to be 151.434 mg/l when 2-Chloro-6,7-dimethoxyquinazolin-4-amine exposed to Daphnia magna for 48hrs. 

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 Daphnia magna was predicted for 2-Chloro-6,7-dimethoxyquinazolin-4-amine (23680-84-4).The EC50 value was estimated to be 151.434 mg/l when 2-Chloro-6,7- dimethoxyquinazolin -4-amine exposed to Daphnia magna for 48hrs. 

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 Daphnia magna was predicted for 2-Chloro-6,7-dimethoxyquinazolin-4-amine (23680-84-4).The EC50 value was estimated to be 151.434 mg/l when 2-Chloro-6,7- dimethoxyquinazolin -4-amine exposed to Daphnia magna for 48hrs. 

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

151.434 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 mobility of daphnia magna. 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 Daphnia magna was predicted for 2-Chloro-6,7-dimethoxyquinazolin-4-amine (23680-84-4).The EC50 value was estimated to be 151.434 mg/l when 2-Chloro-6,7- dimethoxyquinazolin -4-amine exposed to Daphnia magna for 48hrs. 

 

Similarly in the second prediction study was performed based on the prediction done by EPI suite, ECOSAR version 1.1, on the basis of similarity of structure to chemicals for which the aquatic toxicity has been previously measured by structure-activity relationships (SARs) program, the LC 50 value for short term toxicity to aquatic invertebrates was predicted. On the basis of this programe, the LC 50 value for short term toxicity to aquatic invertebrates was predicted to be 301.282 mg/l for 2-chloro-6,7-dimethoxyquinazolin-4 -amine in 48 hrs. Based on this value it can be concluded that the substance 2-chloro-6,7-dimethoxyquinazolin-4-amine is considered to be not toxic to aquatic environment and cannot be classified as per the criteria mentioned in CLP regulation.

 

Similarly in the third weight of evidence study for the read across (738-70-5) Ecotoxicology 2008, Study was conducted to determine the toxicity of chemical 2,4-Diamino-5-(3,4,5-trimethoxybenzyl)-pyrimidin (Trimethoprim) on the mobility of daphnia magna. Test was performed according to the US EPA guideline. Effect concentration of chemical on Freshwater daphnia was tested by static system. Different measured concentration was directly prepared in dilution water. Organisms fed daily during the test. All water parameters measured daily. Immobilization was employed as an endpoint and considered to happen if no movement was detected for 15 s after gentle shaking of the test vehicle. Immobilization measured by probit analysis. After the exposure of chemical EC50 was measured at 24 and 48hrs, EC50 at 24hrs was 155.6 mg/l and at 48hrs 92.0 mg/l. Based on the immobilization of daphnia magna due to the exposure of chemical for 24hrs, the EC50 was 155.6 MG/L with 95% CI: 147.44 -163.700 mg/l. And on the basis of EC50 (155.6 mg/l), 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.

 

Similarly in the fourth weight of evidence study for the read across (738-70-5), Ecotoxicology 2008, Study was conducted to determine the toxicity of chemical 2,4-Diamino-5-(3,4,5-trimethoxybenzyl) pyrimidin (Trimethoprim) on the mobility of Moina macrocopa. Test was performed according to the US EPA guideline. Effect concentration of chemical on Freshwater Moina was tested by static system. Different measured concentration was directly prepared in dilution water.Organisms fed daily during the test. All water parameters measured daily. Immobilization was employed as an endpoint and considered to happen if no movement was detected for 15 s after gentle shaking of the test vehicle. Immobilization measured by probit analysis. After the exposure of chemical EC50 was measured at 24 and 48hrs, EC50 at 24hrs was 144.8 mg/l and at 48hrs 54.8 mg/l. Based on the immobilization of Moina macrocopa due to the exposure of chemical for 24hrs, the EC50 was 144.8 MG/L with (95% CI: 117.3- 172.4 mg/l). And on the basis of EC50 (144.8 mg/l), 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.

 

In the fifth weight of evidence study for the read across chemical (6753-47-5) from ECOTOX 2017, Evaluation of short term toxicity of 1-hydroxy-N,N-bis(2 hydroxypropyl) propan-1-aminium 4-amino-3,5,6-trichloropyridine-2-carboxylate on the growth of aquatic invertebrates. Test conducted by using static method carried out for 96hrs. After the exposure of chemical lethal concentration was measured at which 50% growth inhibited. Based on the rate of mortality of daphnia magna due to the exposure of chemical 1-hydroxy-N,N-bis(2-hydroxypropyl) propan-1-aminium 4-amino-3,5,6-trichloropyridine- 2-carboxylate  with daphnia, the LC50 was 125 mg/l.

 

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, Ecotoxicology 2008, ECOTOX, it was summarized that the chemical was nontoxic and can be consider to be not classified as toxic as per the CLP classification criteria.