Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Type of information:
experimental study planned
Justification for type of information:
TESTING PROPOSAL ON VERTEBRATE ANIMALS

NON-CONFIDENTIAL NAME OF SUBSTANCE:
- Name of the substance on which testing is proposed to be carried out : 4-Hydroxyquinazoline

CONSIDERATIONS THAT THE GENERAL ADAPTATION POSSIBILITIES OF ANNEX XI OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION:
- Available GLP studies :
One Ames test is available. The test item was assessed for its potential to induce gene mutations in the plate incorporation test (experiment I) and the pre-incubation test (experiment II) using Salmonella typhimurium strains TA 1535, TA 1537, TA 98, and TA 100, and the Escherichia coli strain WP2 uvrA.
The test item did not induce gene mutations by base pair changes or frameshifts in the genome of the strains used.
Therefore, the test item is considered to be non-mutagenic in this Salmonella typhimurium and Escherichia coli reverse mutation assay.
One in vitro chromosomal aberration (CA) test is carried out using the Chinese hamster V79 cell line under without and with metabolic activation conditions based on OECD 473.
The test item did induce structural chromosomal aberrations in the V79 Chinese hamster cell line without metabolic activation.
Therefore, the test item is considered to be clastogenic in this chromosome aberration test.

- Available non-GLP studies : No study available

- Historical human data : No data available

- (Q)SAR :
Model Caesar assessment: NON-Mutagenic (good reliability)
Model ISS assessment: NON-Mutagenic (low reliability)
Model SarPy assessment: Possible NON-Mutagenic (moderate reliability)
Model KNN assessment: NON-Mutagen (moderate reliability)

- In vitro methods : One Ames test and one in vitro chromosomal aberration (CA) test are available. Due to negative result in Ames test and positive result in in vitro chromosome aberration test, the in vitro gene mutation test is waived, and an in vivo micronucleus test is proposed.

- Weight of evidence :
Ames test give negative result; In the in vitro chromosome aberration test, the test item did induce structural chromosomal aberrations in the V79 Chinese hamster cell line without metabolic activation, but also cytotoxocity was observed under this condition; the in vitro gene mutation test is waived; the conclusion of classification on the endpoint cannot be drawed, so according to ECHA Guidance on information requirements and chemical safety assessment Chapter R.7a, section R.7.7.6.3, an in vivo micronucleus test is proposed.

- Grouping and read-across : No data available

Data source

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Test material

Constituent 1
Chemical structure
Reference substance name:
Quinazolin-4(1H)-one
EC Number:
207-735-8
EC Name:
Quinazolin-4(1H)-one
Cas Number:
491-36-1
Molecular formula:
C8H6N2O
IUPAC Name:
4-Hydroxyquinazoline
Test material form:
solid

Test animals

Species:
mouse

Results and discussion

Applicant's summary and conclusion

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