Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 600-418-9 | CAS number: 1033-16-5
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Genetic toxicity: in vitro
Administrative data
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 01.10.2010 – 03.12.2010
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 010
- Report date:
- 2010
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
- Version / remarks:
- Council Regulation (EC) No.440/2008. Published in O.J. L 142, 2008
- Deviations:
- yes
- Remarks:
- (see Any other information ...)
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- 2-(3,5-dichloro-2-hydroxyphenyl)-3,4-dihydroquinazolin-4-one
- EC Number:
- 600-418-9
- Cas Number:
- 1033-16-5
- Molecular formula:
- C14H8Cl2N2O2
- IUPAC Name:
- 2-(3,5-dichloro-2-hydroxyphenyl)-3,4-dihydroquinazolin-4-one
- Test material form:
- solid
- Details on test material:
- Expiration: 03/2011
Storage condition of test material: at the room temperature in tightly closed container
Constituent 1
Method
- Target gene:
- gene for histidine or tryptophan synthesis
Species / strainopen allclose all
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Species / strain / cell type:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Metabolic activation system:
- supernatant of rat liver and a mixture of cofactors
- Test concentrations with justification for top dose:
- 30, 100, 300, 1000, 3000 μg
Selection of doses/toxicity:
As the test substance is insoluble in water and relatively bad soluble in acceptable solvents (DMSO 1mg/ml). We tried make a suspension in water, but the test substance vas very little wettable. Behaviour of the test substance in dimethylformamide was similar as in dimethylsulfoxide (DMSO), what is one our favourite non-toxic solvents. So, toxicity test was performed with suspension of the test substance in DMSO in the maximum concentration recommended in guidelines (5000 µg/0.1 mL/ plate).
The test substance was then diluted until formation of concentration series (10-5000 µg per plate), which was tested for toxicity in strain TA 100 without metabolic activation. Particles of the test substance were observable from 500 µg per plate. In the maximum dose of 5000 µg per plate test substance in background made evaluation very difficult and some colonies could be omitted.
Therefore, in the first mutagenicity experiments the dose of 5000 µg per plate was omitted and experiments were done with the maximum dose of 3000 µg per plate. The starting dose was diluted according to the guidelines. The doses used were 30, 100, 300, 1000 and 3000 µg per plate.
The maximum dose was not too suitable for evaluation due to presence of the test substance in the background. This dose was omitted and maximum dose in the second mutagenicity experiments was 1000 µg per plate.
All concentrations of the test substance suspension were dosed in the volume of 0.1 mL per plate. Fresh suspensions of test substance were prepared before each experiment. The suspensions were shaken during dilution, before dosing to the top agar and before pouring onto the plates. - Vehicle / solvent:
- Dimethylsulfoxide for analysis (purity>99.9%), Merck, Lot No. K40982552 019
- Justification for choice of solvent/vehicle: solubility of the substance
Controls
Each experiment included corresponding positive (reference mutagens) and negative controls (untreated control, solvent control). Untreated controls contain no solvent; negative controls contain 0.1 mL of DMSO for injection. All the control numbers were compared with historical ranges of mutant frequencies obtained in our laboratory. The actual numbers were in ranges of the historical numbers.
Controlsopen allclose all
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- Remarks:
- (AS)
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- other: N-methyl-N´-nitro-N-nitrosoguanidine; 4-nitro-o-phenylenediamine; 2-aminofluorene; 2-aminoanthracene; 9-aminoacridine hydrochloride monohydrate;
- Remarks:
- (other: MNNG; NPD; AF; AA; AAc)
- Details on test system and experimental conditions:
- The bacterial tester strains
histidine dependent Salmonella typhimurium TA 98 (CCM 3811), TA 1535 (CCM 3814), and tryptophan dependent strain Escherichia coli WP2 uvrA (CCM 4751) - were obtained from Czech Collection of Microorganisms (CCM) of Masaryk University, Brno
and TA100 (CIP 103796, lot. No.1008) and TA 1537 (CIP 103799, lot No. 34508) were from Biological Resource Center of Institut Pasteur (CRBIP), Paris.
Strains TA 1537 and TA 98 detect frame shift mutations, strains TA 100 and TA 1535 serve to detect base-pair substitution mutations, and strain E.coli WP2 uvrA detects cross-linking mutagens.
METHOD OF APPLICATION: in medium; in agar (plate incorporation)
NUMBER OF REPLICATIONS: two series
DETERMINATION OF CYTOTOXICITY
- Method: relative total growth - Evaluation criteria:
- The main criterion for evaluation of results was modified two-fold increase rule, which is compatible with the application of statistical methods (2, 3). After this rule the result is positive, if a reproducible doseresponse effect occurs and/or a doubling of the ratio Rt/Rc is reached.
- Statistics:
- For the evaluation of results, the modified two-fold increase rule was used, which is compatible with the application of statistical methods:
Dunkel V. C.. Chu K.C. (1980): Evaluation of methods for analysis of microbial mutagenicity assays in The Predictive Value of Short-Term Screening Tests in Carcinogenicity Evaluation. Elsevier North-Holland Biomedical Press. 231 - 417
Claxton L. D. et al. (1987): Guide for the Salmonella typhimurium/mammalian microsome tests for bacterial mutagenicity. Mutat. Res. 189. 83 - 91
Results and discussion
Test resultsopen allclose all
- Key result
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not determined
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not determined
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not determined
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not determined
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- HISTORICAL CONTROL DATA:
Each experiment included corresponding positive (reference mutagens) and negative controls (untreated control, solvent control). Untreated controls contain no solvent; negative controls contain 0.1 mL of DMSO. All the control numbers were compared with historical ranges of mutant frequencies obtained in our laboratory. The actual numbers were in ranges of the historical numbers.
ADDITIONAL INFORMATION ON CYTOTOXICITY:
As the test substance is insoluble in water and relatively bad soluble in acceptable solvents (DMSO 1mg/ml). We tried make a suspension in water, but the test substance vas very little wettable. Behaviour of the test substance in dimethylformamide was similar as in dimethylsulfoxide (DMSO), what is one our favourite non-toxic solvents. So, toxicity test was performed with suspension of the test substance in DMSO in the maximum concentration recommended in guidelines (5000 µg/0.1 mL/ plate).
The test substance was then diluted until formation of concentration series (10-5000 µg per plate), which was tested for toxicity in strain TA 100 without metabolic activation. Particles of the test substance were observable from 500 µg per plate. In the maximum dose of 5000 µg per plate test substance in background made evaluation very difficult and some colonies could be omitted.
Therefore, in the first mutagenicity experiments the dose of 5000 µg per plate was omitted and experiments were done with the maximum dose of 3000 µg per plate. The starting dose was diluted according to the guidelines. The doses used were 30, 100, 300, 1000 and 3000 µg per plate.
The maximum dose was not too suitable for evaluation due to presence of the test substance in the background. This dose was omitted and maximum dose in the second mutagenicity experiments was 1000 µg per plate.
All concentrations of the test substance suspension were dosed in the volume of 0.1 mL per plate. Fresh suspensions of test substance were prepared before each experiment. The suspensions were shaken during dilution, before dosing to the top agar and before pouring onto the plates.
Applicant's summary and conclusion
- Conclusions:
- Under the above-described experimental design, the test substance 2-(3',5'-Dichloro-2'-hydroxyphenyl)-4-quinazolinone was non-mutagenic for all the Salmonella typhimurium as well as Escherichia coli strains both in experiments without and with metabolic activation.
- Executive summary:
Test substance 2-(3',5'-Dichloro-2'-hydroxyphenyl)-4-quinazolinone was assayed for the mutagenicity by the Bacterial Reverse Mutation Test. The test was performed according to EU method B.13/14 Mutagenicity – Reverse mutation test using bacteria, which is analogous to the OECD Test Guideline No. 471.
Four indicator Salmonella typhimurium strains TA 98, TA 100, TA 1535 and TA 1537 and one indicator Escherichia coli WP2 uvrA strain were used. The test substance was suspended in DMSO and assayed in doses of 10-3000 ug which were applied to plates in volumes of 0.1 mL.
Two series of experiments were performed with each strain - without metabolic activation and with a supernatant of rat liver and a mixture of cofactors.
In the arrangement given above, the test substance 2-(3',5'-Dichloro-2'-hydroxyphenyl)-4-quinazolinone was non-mutagenic for all the used bacterial strains with as well as without metabolic activation.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.