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EC number: 214-772-3 | CAS number: 1193-24-4
- 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
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
Ames test: negative (S. typhimurium TA98, TA100, TA1535, TA1537), OECD 471, Ebert 1995
Ames test: negative (S. typhimurium TA1535, TA100, TA97, TA98), NTP 1996
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1996 or before
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- Published under the US National Toxicology Program, according to the quality rules of the NTP interagency program ("best science available"). Experimental details well documented, but no explicit reference to GLP. Only four S. typhimurium strains, but no E. coli tested.
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.5265 (The Salmonella typhimurium Bacterial Reverse Mutation Test)
- Version / remarks:
- No explicit reference to this guideline
- GLP compliance:
- not specified
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- hisG46, hisD3052, hisC3076 (from choice of strains)
- Species / strain / cell type:
- S. typhimurium TA 1535
- Species / strain / cell type:
- S. typhimurium TA 100
- Species / strain / cell type:
- S. typhimurium TA 97
- Species / strain / cell type:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Metabolic activation system:
- Aroclor 1254-induced male Sprague-Dawley rat liver S9, 10% and 30%; Aroclor 1254-induced male Syrian hamster liver S9, 10% and 30%
- Test concentrations with justification for top dose:
- 100, 333, 1000, 3333, 10000 microgram/plate
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: water
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- water
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 2-nitrofluorene
- Remarks:
- without metabolic activation
Migrated to IUCLID6: for TA 98; sodium azide (TA100 + TA1535); 9-aminoacridine (TA97) - Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- water
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 2-aminoanthracene (all strains)
- Remarks:
- with metabolic activation
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: preincubation
DURATION
- Preincubation period: 20 minutes at 37°
- Exposure duration: 2 days
NUMBER OF REPLICATIONS:
- not stated; sufficient to calculate mean and standard error of mean
NUMBER OF CELLS EVALUATED:
- no data - Evaluation criteria:
- Significant increase of mutant colonies over spontaneous control rate
Pattern and strength of mutant response
Verification of response in repeat test - Statistics:
- Mean and standard error of mean (SEM)
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Remarks:
- no toxicity up to 10000 microgram/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Remarks:
- no toxicity up to 10000 microgram/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 97
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Remarks:
- no toxicity up to 10000 microgram/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Remarks:
- no toxicity up to 10000 microgram/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results (migrated information):
negative
The results are sufficiently detailed and unambiguous as to be reliable for risk assessment, classification and labeling. - Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1995-08-01 to 1995-09-04
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- GLP study according to OECD guideline. Only four strains of S. typhimurium were tested, but no strain of E. coli. One or more concentrations insoluble in the final treatment mixture (precipitating) were not tested; a saturated aqueous solution of the test material (2.5 mg/liter) served as a stock solution for the preparation of the final treatment mixtures, thus only amounts up to approximately 500 microgram/plate were investigated.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- yes
- Remarks:
- Only 4 strains of S. typhimurium, no E.coli strain tested. No precipitating concentration tested; maximum amount 500 microgram/plate.
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
- Deviations:
- yes
- Remarks:
- Only 4 strains of S. typhimurium, no E.coli strain tested. No precipitating concentration tested; maximum amount 500 microgram/plate.
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- hisG46, hisD3052, hisC3076
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Additional strain / cell type characteristics:
- not specified
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 fraction (lot # 170795, Cytotest Cell Research , Rossdorf, Germany) induced with Aroclor 1254
- Test concentrations with justification for top dose:
- Test #1: Plate incorporation test: 5, 16, 50, 160, 501 microgram/plate
Test #2: Preincubation test: 5, 15, 48, 154, 482 microgram/plate - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: water
- Justification for choice of solvent/vehicle: The solubility of the test material in ten different solvents was tested; water turned out to be the most suitable, with a maximum solubility of 2.5 g/liter - Untreated negative controls:
- yes
- Remarks:
- 0.2 mL water
- Negative solvent / vehicle controls:
- yes
- Remarks:
- 0.2 mL water
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 2-nitrofluorene
- Remarks:
- Without metabolic activation
Migrated to IUCLID6: for TA98; sodium azide for TA100 and TA1535, 9-aminoacridine for TA1537 - Untreated negative controls:
- yes
- Remarks:
- 0.2 mL water
- Negative solvent / vehicle controls:
- yes
- Remarks:
- 0.2 mL water
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 2-aminoanthracene
- Remarks:
- With metabolic activation
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: Test #1: in agar (plate incorporation), Test #2: preincubation
DURATION
- Preincubation period: 30 min at 30°C
- Exposure duration (incubation time): 72 hours at 37°C
NUMBER OF REPLICATIONS: Triplicate, per strain and concentration of the test material
NUMBER OF CELLS EVALUATED: >=67'000'000 per plate
DETERMINATION OF CYTOTOXICITY
- other: examination of the bacterial background lawn - Evaluation criteria:
- VALIDITY:
- Characteristic mean number of spontaneous revertants in solvent control
- Titers of overnight cultures > 100'000'000
- Significant increase in the number of revertants in the mean of each positive control, compared with the mean of the solvent control
- At least four non-toxic dose levels
EVALUATION:
- At least a doubling in the mean revertants per plate of at least one tester strain (in two independent experiments)
- This increase must be accompanied by a dose response to increasing concentrations of the test article
- Single increases in revertant frequencies (not dose-related, not reproducible in independent tests) are considered non-relevant
- If such increases occur in both independent tests, this will be taken as an indication of a mutagenic effect - Statistics:
- Mean and standard deviation of replications
Test compound / control ratio: Mean no. of colonies/plate (test compound) / mean no. of colonies/plate (water) - Species / strain:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Remarks:
- up to 500 microgram/plate
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Remarks:
- up to 500 microgram/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: Not tested (pH of suspension: 3.9)
- Effects of osmolality: Not expected due to limited solubility
- Evaporation from medium: Not expected (solid, melting point >300°C
- Water solubility: 2.5 g/liter, this limited the maximum concentration introduced into the test system to approx. 500 microgram/plate. No concentrations were tested that were insoluble in the final treatment mixture.
- Precipitation: Not observed
- Other confounding effects: None
RANGE-FINDING/SCREENING STUDIES: None
COMPARISON WITH HISTORICAL CONTROL DATA: No data
ADDITIONAL INFORMATION ON CYTOTOXICITY: A reduced growth of the bacterial background lawn, indicative of test compound induced cytotoxicity, was not detectable with any of the tester strains - Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results (migrated information):
negative
The results are sufficiently detailed and unambiguous as to be reliable for risk assessment, classification and labeling.
Referenceopen allclose all
Only 4 strains of S. typhimurium, no E.coli strain tested. No precipitating concentration tested; maximum amount 500 microgram/plate.In both experiments (test #1: plate incorporation test; test #2: preincubation test) no indication of test compound induced mutagenicity was observed with either one of the tester strains TA 98, TA 100, TA 1535 and TA 1537, with or without metabolic activation by S9 mix.
Under the experimental conditions described, 4,6-dihydroxypyrimidine did not induce a mutageniceffect in four strains of S.typhimurium. It is therefore not considered to be a bacterial mutagen.
All criteria for a valid study were met according to the author: All tested bacterial strains exhibited a positive mutagenic response with the positive controls (with and without metabolic activation). Negative controls (water) were also tested with each strain, and the mean numbers of spontaneous revertants were considered acceptable. However, no concentrations insoluble in the final treatment mixture were tested, and the concentration for a limit test (5000 microgram/plate) was not reached.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Ames test (bacterial reverse mutation in vitro): Negative
The study by Ebert (Huels,1995) is a completely documented company study report on Ames testing, under GLP and according to the OECD guideline 471 valid at the time of testing. Limitations are the low maximum concentrations applied (only 500 microgram/plate, non-precipitating), and the absence of E. coli tester strains, which are required by newer versions of the guideline OECD 471. Only S. typhimurium strains TA98, TA100, TA1535 and TA1537 were investigated.
The NTP study (1996) follows equally high scientific standards, but is documented in less detail. Again, only S. typhimurium strains were investigated (TA 1535, TA 100, TA97, and TA98). Doses up to 10000 microgram/plate were applied, without signs of precipitation or cytotoxicity.
Both studies show negative results for all strains tested, with and without metabolic activation.
It is known that the strains used in the two studies may not detect certain oxidizing mutagens, cross-linking agents and hydrazines, but since the test substance 4,6-dihydroxypyrimidine has neither of these properties, we believe that the missing E. coli strain does not disqualify the negative results obtained.
Based on a weight-of-evidence approach, according to Regulation (EC) No. 1907/2006, Annex XI, section 1.2., we conclude that 4,6-dihydroxypyrimidine is non-nutagenic in the Ames test.
Chromosome aberration: No data available
Justification for classification or non-classification
The Ebert (Huels, 1995) and the NTP (1996) studies are considered reliable with restrictions but adequate for the purposes of risk assessment, classification and labeling.
Based on the results of the Ebert (Huels, 1995) and the NTP (1996) studies, the substance does not meet the criteria for classification under Regulation (EC) No. 1272/2008 Annex I, Part 3, 3.5.2.
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