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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

Skin irritation:

The dermal irritation potential of 2-chloro-6,7-dimethoxyquinazolin-4-amine (CAS No: 23680-84-4) was estimated using OECD QSAR toolbox version 3.4 with logPow as the primary descriptor. The substance 2-chloro-6,7-dimethoxyquinazolin-4-amine (CAS No: 23680-84-4) was estimated to be not irritating to the skin of New Zealand White rabbits. Based on the estimated result 2-chloro-6,7-dimethoxyquinazolin-4-amine (CAS No: 23680-84-4) can be considered to be not irritating to skin and can be classified under the category ˋ Not Classified’ as per CLP regulation.

 

Eye irritation:

The ocular irritation potential of 2-chloro-6,7-dimethoxyquinazolin-4-amine (CAS No: 23680-84-4) was estimated using OECD QSAR toolbox version 3.4 with logPow as the primary descriptor. The substance 2-chloro-6,7-dimethoxyquinazolin-4-amine (CAS No: 23680-84-4) was estimated to be not irritating into the eyes of New Zealand White rabbits. Based on the estimated result 2-chloro-6,7-dimethoxyquinazolin-4-amine (CAS No: 23680-84-4) can be considered to be not irritating to eye and can be classified under the category ˋ Not Classified’ as per CLP regulation.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
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 QMRF report has been attached
Qualifier:
according to guideline
Guideline:
other: estimated data
Principles of method if other than guideline:
Prediction is done using QSAR Toolbox version 3.4
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
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
No data available
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
not specified
Controls:
not specified
Amount / concentration applied:
No data available
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3
Details on study design:
No data available
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
72 h
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No skin irritation was observed in treated rabbits.

Estimation method: Takes mode 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 ("i" and ( not "j") )  )  and ("k" and "l" )  )

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 No alert found by DNA binding by OECD ONLY

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as High (Class III) by Toxic hazard classification by Cramer (extension) ONLY

Domain logical expression index: "h"

Similarity boundary:Target: COc1cc2c(cc1OC)c(N)nc(Cl)n2
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "i"

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: "j"

Referential boundary: The target chemical should be classified as Bromine, olefinic attach [-Br] by Organic functional groups (US EPA)

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.263

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.56

Interpretation of results:
other: not irritating
Conclusions:
The substance 2-chloro-6,7-dimethoxyquinazolin-4-amine (CAS No: 23680-84-4) was estimated to be not irritating to the skin of New Zealand White rabbits. Based on the estimated result 2-chloro-6,7-dimethoxyquinazolin-4-amine (CAS No: 23680-84-4) can be considered to be not irritating to skin.
Executive summary:

The dermal irritation potential of 2-chloro-6,7-dimethoxyquinazolin-4-amine (CAS No: 23680-84-4) was estimated using OECD QSAR toolbox version 3.4 with logPow as the primary descriptor. The substance 2-chloro-6,7-dimethoxyquinazolin-4-amine (CAS No: 23680-84-4) was estimated to be not irritating to the skin of New Zealand White rabbits. Based on the estimated result 2-chloro-6,7-dimethoxyquinazolin-4-amine (CAS No: 23680-84-4) can be considered to be not irritating to skin and can be classified under the category ˋ Not Classified’ as per CLP regulation.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
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 QMRF report has been attached
Qualifier:
according to guideline
Guideline:
other: estimated data
Principles of method if other than guideline:
Prediction is done using 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
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
No data available
Vehicle:
not specified
Controls:
not specified
Amount / concentration applied:
No data available
Duration of treatment / exposure:
single application
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3
Details on study design:
No data available
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
72 h
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No known signs of ocular lesions were observed.

Estimation method: Takes mode value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

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

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 SNAr AND SNAr >> Nucleophilic aromatic substitution AND SNAr >> Nucleophilic aromatic substitution >> Halo-pyrimidines by Protein binding by OECD

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct Acylation Involving a Leaving group OR Acylation >> Direct Acylation Involving a Leaving group >> Acetates OR No alert found OR SN2 OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Allyl acetates and related chemicals OR SNAr >> Nucleophilic aromatic substitution >> Activated halo-benzenes OR SNAr >> Nucleophilic aromatic substitution >> Activated halo-pyridines OR SNAr >> Nucleophilic aromatic substitution >> Halo-triazines by Protein binding by OECD

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Not known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Metal atoms were identified OR Not covered by current version of the decision tree by DART scheme v.1.0

Domain logical expression index: "i"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.295

Domain logical expression index: "j"

Parametric boundary:The target chemical should have a value of log Kow which is <= 5.46

Interpretation of results:
other: not irritating
Conclusions:
The substance 2-chloro-6,7-dimethoxyquinazolin-4-amine (CAS No: 23680-84-4) was estimated to be not irritating into the eyes of New Zealand White rabbits. Based on the estimated result 2-chloro-6,7-dimethoxyquinazolin-4-amine (CAS No: 23680-84-4) can be considered to be not irritating to eye.
Executive summary:

The ocular irritation potential of 2-chloro-6,7-dimethoxyquinazolin-4-amine (CAS No: 23680-84-4) was estimated using OECD QSAR toolbox version 3.4 with logPow as the primary descriptor. The substance 2-chloro-6,7-dimethoxyquinazolin-4-amine (CAS No: 23680-84-4) was estimated to be not irritating into the eyes of New Zealand White rabbits. Based on the estimated result 2-chloro-6,7-dimethoxyquinazolin-4-amine (CAS No: 23680-84-4) can be considered to be not irritating to eye and can be classified under the category ˋ Not Classified’ as per CLP regulation.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

Various studieshas been investigated for the test chemical2-chloro-6,7-dimethoxyquinazolin-4-amine (CAS No: 23680-84-4)to observe the potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits for target chemical2-chloro-6,7-dimethoxyquinazolin-4-amine (CAS No: 23680-84-4) and its structurally similar read across substances4-Chloro-2,5-dimethoxyaniline (CAS no: 6358-64-1)and 2,4-diamino-6-phenyl-1,3,5-triazine (CAS no: 91-76-9).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

 

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the skin irritation potential was estimated for test chemical2-chloro-6,7-dimethoxyquinazolin-4-amine (CAS No: 23680-84-4) .The chemical 2-chloro-6,7-dimethoxyquinazolin-4-amine (CAS No: 23680-84-4) is estimated to be not irritating to skin of New Zealand White rabbits.

The IFA GESTIS {GESTIS SUBSTANCE Database (information system in hazardous substance of the Berufsgenossenscheftn)} conducted skin irritation study of read across substance 4-Chloro-2,5-dimethoxyaniline (CAS no: 6358-64-1) on rabbits according to OECD 404 that supports the above mentioned results. The chemical did not produce any adverse skin effects when applied dermally. Therefore under the test condition, the chemical 4-Chloro-2,5-dimethoxyaniline (CAS no: 6358-64-1)was considered to be not irritating to the rabbits’ skin.

 

The above results were further supported by the dermal irritation study reported by OECD SIDS { SIDS Initial Assessment Report For SIAM 13, OECD SIDS, November 2001} for read across substance 2,4-diamino-6-phenyl-1,3,5-triazine in (CAS no: 91-76-9) on three female New Zealand white albino rabbits in accordance with the OECD Guide-line 404 "Acute Dermal Irritation/Corrosion". The chemical was applied dermally for the 4 hours exposure period under occlusive condition and later observed for skin reactions.No known signs of irritation and systematic toxicity were observed in any of the treated rabbits. Hence,2,4-diamino-6-phenyl-1,3,5-triazine (CAS no: 91-76-9) can be considered to be not irritating to rabbits’ skin.

 

Thus on the basis of available data for thetarget chemical2-chloro-6,7-dimethoxyquinazolin-4-amine (CAS No: 23680-84-4) and its structurally similar read across substances4-Chloro-2,5-dimethoxyaniline (CAS no: 6358-64-1)and 2,4-diamino-6-phenyl-1,3,5-triazine (CAS no: 91-76-9),it can be concluded thatchemical 2-chloro-6,7-dimethoxyquinazolin-4-amine (CAS No: 23680-84-4) is unable to cause skin irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Eye irritation:

In different studies,the test chemical2-chloro-6,7-dimethoxyquinazolin-4-amine (CAS No: 23680-84-4) has been investigated for potential for ocular irritationto a greater or lesser extent. The studies are based on in vivo experiments in rabbits for target chemical2-chloro-6,7-dimethoxyquinazolin-4-amine (CAS No: 23680-84-4)its structurally similar read across substances4-Chloro-2,5-dimethoxyaniline (CAS no: 6358-64-1)and 2,4-diamino-6-phenyl-1,3,5-triazine (CAS no: 91-76-9).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

 

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the eye irritation potential was estimated for test chemical2-chloro-6,7-dimethoxyquinazolin-4-amine (CAS No: 23680-84-4) .The chemical 2-chloro-6,7-dimethoxyquinazolin-4-amine (CAS No: 23680-84-4) is estimated to be not irritating to eye of New Zealand White rabbits.

 

The IFA GESTIS {GESTIS SUBSTANCE Database (information system in hazardous substance of the Berufsgenossenscheftn)} conducted an ocular irritation study of read across substance 4-Chloro-2,5-dimethoxyaniline (CAS no: 6358-64-1) on rabbits according to OECD 405 that supports the above mentioned results.The chemical triggered only minor irritations that subsided within 72 hours when installed into the eyes of each rabbits. Therefore under the test condition, the chemical 4-Chloro-2,5-dimethoxyaniline (CAS no: 6358-64-1)was considered to be not irritating to the rabbits’ eye.

 

The above results were further supported by an eye irritation study reported by OECD SIDS { SIDS Initial Assessment Report For SIAM 13, OECD SIDS, November 2001} for read across substance 2,4-diamino-6-phenyl-1,3,5-triazine in (CAS no: 91-76-9)on rabbitsas perDirective 84/449/EEC, B.5 "Acute Toxicity (eye irritation)" Guidelines.About 94 mg of undiluted2,4-diamino-6-phenyl-1,3,5-triazine was instilled into eyes of 3 rabbits. The rabbits were observed and scored for signs of irritation at 1, 24, 48 and 72 hours.The mean irritation scores were classifiedfollowing the scheme of Kay and Calandra.In all three animals only the conjunctivae was affected. All effects were reversible within 72 hours (3 day). No effects on the cornea or iris were observed in the treated animals. Treatment of the eyes with fluorescein 24 hours after instillation of the test substance did not reveal any corneal epithelial damage. No signs of systemic toxicity were observed.The mean Draize scores after 1 hour was 4.0 and after 72 hours was 0.0.2,4-diamino-6-phenyl-1,3,5-triazineshould be classified as mildly irritating following thescheme of Kay and Calandra. According to the EEC criteria for classification and labelling,2,4-diamino-6-phenyl-1,3,5-triazineneed not to be labelled as an eye irritant.Hence,2,4-diamino-6-phenyl-1,3,5-triazine (CAS no: 91-76-9) can be considered to be not irritating to rabbit eyes.

 

Thus on the basis of available data for thetarget chemical2-chloro-6,7-dimethoxyquinazolin-4-amine (CAS No: 23680-84-4) and its structurally similar read across substances4-Chloro-2,5-dimethoxyaniline (CAS no: 6358-64-1)and 2,4-diamino-6-phenyl-1,3,5-triazine (CAS no: 91-76-9),it can be concluded thatchemical 2-chloro-6,7-dimethoxyquinazolin-4-amine (CAS No: 23680-84-4) is unable to cause eye irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Justification for classification or non-classification

The skin and eye irritation potential of test chemical 2-chloro-6,7-dimethoxyquinazolin-4-amine (CAS No: 23680-84-4) and its structurally similar read across substanceswere observed in various studies. The results obtained from these studies indicate that the chemical 2-chloro-6,7-dimethoxyquinazolin-4-amine (CAS No: 23680-84-4) is unlikely to cause skin and eye irritation. Hence 2-chloro-6,7-dimethoxyquinazolin-4-amine (CAS No: 23680-84-4) can be classified under the category “Not Classified” for skin and eye as per CLP.