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EC number: 248-273-7 | CAS number: 27157-94-4
- 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
OECD 471, Salmonella typhimurium strains TA 98, TA 100, TA 102, TA 1535 and TA 1537 with and without metabolic activation: negative
OECD 473,chromosome aberration in mammalian cells (human peripheral lymphocytes) with and without metabolic activation: negative
OECD 476, HPRT-V79 mammalian cell mutagenicity test with and without metabloic activation: negative
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:
- key study
- Study period:
- 2012
- Reliability:
- 1 (reliable without restriction)
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- Strain Designation Histidine Gene Locus Affected Additional Mutations Type of Mutation Detected
Repair LPS Plasmids
TA 98#1 his D 3052 uvr B- rfa- pKM 101 Frameshift
TA 100#1 his G 46 uvr B- rfa- pKM 101 Base-pair substitution
TA 102#1 his G 428 wild-type rfa- pKM 101 / pAQ1 Base-pair substitution
TA 1535#2 his G 46 uvr B- rfa- none Base-pair substitution
TA 1537#2 his C 3076 uvr B- rfa- none Frameshift
rfa-: partial loss of lipopolysaccharide (LPS) barrier that causes increased permeability to macromolecules
uvr B-: loss of DNA excision repair system
pKM 101: R-factor plasmid, thought to cause an increased error-prone DNA repair
pAQ1: plasmid, carrier of tetracycline resistance
#1 resistance to Ampicillin
#2 non-resistance to Ampicillin - Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
- Metabolic activation:
- with and without
- Metabolic activation system:
- a microsomal preparation derived from Aroclor 1254-induced rat liver.
- Test concentrations with justification for top dose:
- 5.0, 15.8, 50, 158, 500 and 1580 µg per plate
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: ethanol (Batch no. B1810; Honeywell Specialty Chemicals Seelze GmbH, 30926 Seelze Germany)
- Justification for choice of solvent/vehicle: Cresyl-P1 (DANAFLOAT™ 070) was not soluble in dimethyl sulfoxid (DMSO), water, methanol or acetone. - Untreated negative controls:
- yes
- Remarks:
- ethanol
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- Remarks:
- in aqua ad iniectabilia (10 µg/plate) : TA 1535, TA 100
- Untreated negative controls:
- yes
- Remarks:
- ethanol
- Positive controls:
- yes
- Positive control substance:
- 2-nitrofluorene
- Remarks:
- in DMSO (10 µg/plate) : TA 98
- Untreated negative controls:
- yes
- Remarks:
- ethanol
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- Remarks:
- in ethanol, abs. (100 µg/plate) : TA 1537
- Untreated negative controls:
- yes
- Remarks:
- ethanol
- Positive controls:
- yes
- Positive control substance:
- mitomycin C
- Remarks:
- in DMSO (10 µg/plate) : TA 102
- Untreated negative controls:
- yes
- Remarks:
- ethanol
- Positive controls:
- yes
- Positive control substance:
- benzo(a)pyrene
- Remarks:
- in DMSO (10 µg/plate) : TA 98, TA 102, TA 1537
- Untreated negative controls:
- yes
- Remarks:
- ethanol
- Positive controls:
- yes
- Positive control substance:
- other: 2-amino-anthracene
- Remarks:
- in DMSO (2 µg/plate) : TA 100, TA 1535
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation)
DURATION
- Preincubation period: 20 minutes at 37°C
- Exposure duration: 48-72 hours at 37°C - Evaluation criteria:
- A test item is considered to show a positive response if
- the number of revertants is significantly increased (p ≤ 0.05, U-test according to MANN and WHITNEY, see COLQUHOUN, D.: Lectures on Biostatistics, Clarendon Press, Oxford (1971)) compared with the solvent control to at least 2-fold of the solvent control for TA 98, TA 100 and TA 102 and 3-fold of the solvent control for TA 1535 and TA 1537 in both independent experiments;
- in addition, a significant (p ≤ 0.05) concentration (log value)-related effect (Spearman’s rank correlation coefficient, see COLQUHOUN, D.: Lectures on Biostatistics, Clarendon Press, Oxford (1971)) is observed;
- positive results have to be reproducible and the histidine independence of the revertants has to be confirmed by streaking random samples on histidine-free agar plates. - Species / strain:
- S. typhimurium TA 102
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Remarks:
- No increase in revertant colony numbers as compared with control counts was observed for test item, tested up to a cytotoxic concentration of 3250 µg/plate, in any of the 5 test strains in two independent experiments w./wo metabolic activation, respective
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- In the plate incorporation test and the preincubationcubation test, each carried out without and with metabolic activation cytotoxicity (scarce background lawn and reduction of the number of revertants) was noted at the top concentration of 1580 µg /plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Conclusions:
- It can be concluded that the test material is negative with and without metabolic activation in all tester strains.
Under the present test conditions Cresyl-P1 tested up to a cytotoxic concentration of 1580 µg Cresyl-dtp/plate, caused no mutagenic effect in the Salmonella typhimurium strains TA 98, TA 100, TA 102, TA 1535 and TA 1537 neither in the plate incorporation test nor in the preincubation test each carried out without and with metabolic activation. - Executive summary:
The registered substance was tested for its mutagenicity in an Ames Plate Incorporation Assay according to OECD Guideline 471 and under GLP in Salmonella typhimurium strains TA 98, TA 100, TA 102, TA 1535 and TA 1537 with and without metabolic activation.
Under the present test conditions Cresyl-P1 tested up to a cytotoxic concentration of 1580 µg Cresyl-dtp/plate, caused no mutagenic effect in the Salmonella typhimurium strains TA 98, TA 100, TA 102, TA 1535 and TA 1537 neither in the plate incorporation test nor in the preincubation test each carried out without and with metabolic activation.- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2012
- Reliability:
- 1 (reliable without restriction)
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.10 (Mutagenicity - In Vitro Mammalian Chromosome Aberration Test)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- in vitro mammalian chromosome aberration test
- Species / strain / cell type:
- mammalian cell line, other: HUMAN PERIPHERAL LYMPHOCYTES
- Metabolic activation:
- with and without
- Test concentrations with justification for top dose:
- Tests without metabolic activation (4- and 24-hour exposure)
31.3, 62.5 or 125 µg Cresyl-P1/mL medium (4-h exposure), in the absence of metabolic activation
15.3, 31.3 or 62.5 µg Cresyl-P1/mL medium (24-h exposure), in the absence of metabolic activation
Test with metabolic activation (4-hour exposure)
62.5, 125 or 250 µg Cresyl-P1/mL medium in the presence of metabolic activation - Vehicle / solvent:
- Ethanol (Batch no. B1810; Honeywell Specialty Chemicals Seelze GmbH, 30926 Seelze Germany)
Cresyl-P1 was not soluble in DMSO, water, methanol or acetone. - Untreated negative controls:
- yes
- Remarks:
- Ethanol
- Positive controls:
- yes
- Positive control substance:
- mitomycin C
- Remarks:
- was used as the positive control for the study in the absence of metabolic activation.
- Untreated negative controls:
- yes
- Remarks:
- Ethanol
- Positive control substance:
- cyclophosphamide
- Remarks:
- was used as the positive control for the study in the presence of metabolic activation.
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
DURATION
- Exposure duration: 4 hours and 24 in the absence of metabolic activation.4 hours in the presence of metabolic activation.
SPINDLE INHIBITOR (cytogenetic assays): colcemid® to accumulate cells in a metaphase-like stage of mitosis (c-metaphase). - Evaluation criteria:
- The test item is judged to have mutagenic properties with respect to chromosomal or chromatid change, if the following criteria are fulfilled:
o the number of chromosomal aberrations is significantly (at p ≤ 0.05) increased compared with the solvent control
o the increase observed is concentration-dependent
o both duplicate cultures lead to similar results
o the increase should not occur in the severely cytotoxic range (mitotic index <0.25), as it is known that high cytotoxicity causes artefacts in the form of aberrations in in vitro chromosomal aberration tests
o a reproducible increase in the number of cells with chromosomal aberrations. - Statistics:
- The assessment was carried out by a comparison of the number of chromosome aberrations of the samples with those of the solvent control, using the exact test of R. A. FISHER (p ≤ 0.05) as recommended by the UKEMS guidelines (The United Kingdom Branch of the European Environmental Mutagen Society: Report of the UKEMS subcommittee on guidelines for mutagenicity testing, part III, Statistical evaluation of mutagenicity test data, 1989).
- Species / strain:
- mammalian cell line, other: HUMAN PERIPHERAL LYMPHOCYTES
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Conclusions:
- The registered substance was found to be negative with metabolic activation and negative without metabolic activation.
Under the present test conditions, Cresyl-P1, tested up to cytotoxic concentrations, in the absence and in the presence of metabolic activation employing two exposure times (without S9) and one exposure time (with S9) revealed no indications of mutagenic properties with respect to chromosomal or chromatid damage.
In the same test, Mitomycin C and cyclophosphamide induced significant damages, which confirmed the validity of this assay. - Executive summary:
The registered substance was tested for its potential to induce chromosome aberrations in an Chromosome Aberration study in mammalian cells (human peripheral lymphocytes) according to OECD Guideline 473 and under GLP, with and without metabolic activation.
Under the present test conditions, Cresyl-P1, tested up to cytotoxic concentrations, in the absence and in the presence of metabolic activation employing two exposure times (without S9) and one exposure time (with S9) revealed no indications of mutagenic properties with respect to chromosomal or chromatid damage.
In the same test, Mitomycin C and cyclophosphamide induced significant damages, which confirmed the validity of this assay.- Endpoint:
- in vitro gene mutation study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2018
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.17 (Mutagenicity - In Vitro Mammalian Cell Gene Mutation Test)
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- other: In Vitro Mammalian Cell Gene Mutation Tests using the Hprt and xprt genes
- Target gene:
- HPRT locus. This gene is situated in man, hamster and other species at the X-chromosome. The gene product, hypoxanthine guanine phosphoribosyl transferase, an enzyme which is not vital for the cell, activates the purine analogues 8-azaguanine and 6-thioguanine (used in this assay) to toxic metabolites. Mutants which do not express the active enzyme are resistant to high concentrations of 6-thioguanine or 8-azaguanine. Such mutants can be obtained by a forward mutation of the hprt locus.
- Species / strain / cell type:
- Chinese hamster lung fibroblasts (V79)
- Details on mammalian cell type (if applicable):
- - Type and identity of media: Dulbecco's modified Eagle-Medium supplemented with 10% fetal calf serum2, penicillin2 (100 U/mL) and streptomycin2 (100 µg/mL) called DMEM-FCS. Cultures are incubated at 37°C in a humidified atmosphere (90%) containing 10% CO2. For subculturing, a trypsin (0.05%)-EDTA (ethylene¬diamine¬tetra¬acetic acid, 0.02%) solution in modified Puck's salt solution A2 is used. Exposure to the test item in the presence of S9 mix is performed in Dulbecco's phosphate buffered saline (PBS)2 which additionally contained 20 mM HEPES (N'-2-hydroxyethylpiperazine-N'-2-ethane-sulfonic acid)2 pH 7.4 (PBS-HEPES). The cells are periodically checked for the absence of mycoplasma contamination by using the HOECHST stain 33258. The spontaneous mutation rate is continuously monitored.
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes
- Periodically checked for karyotype stability: yes/no
- Periodically "cleansed" against high spontaneous background: yes - Additional strain / cell type characteristics:
- not applicable
- Metabolic activation:
- with and without
- Metabolic activation system:
- a microsomal preparation derived from Aroclor 1254-induced rat liver.
- Test concentrations with justification for top dose:
- Preliminary cytotoxicity test
The concentrations to be employed in the main experiment were chosen based on the results of a preliminary cytotoxicity study without and with metabolic activation with concentrations of 3.16, 10.0, 31.6, 100, 316, 1000 and 2000 µg/mL medium. In this preliminary test cytotoxicity in form of decreased relative survival compared to the control was noted starting at concentrations of 31.6 or 316 µg/mL medium in the experiments without and with metabolic activation. Test item precipitation was noted macroscopically starting at a concentration of 100 µg/mL medium in the experiments without and with S9 mix. Complete cytotoxicity was noted at concentrations of 1000 and 2000 µg/mL medium in both experiments (see Table 1). No changes in pH or osmolality were noted in the test cultures compared to the negative control treated with DMSO. For details see the Text table 5-1. Hence, 400 µg Cresyl-P1/mL medium was employed as highest concentration for the genotoxicity tests without and with metabolic activation in the main experiment.
Main study
Concentrations of 25, 50, 100, 200 and 400 µg Cresyl-P1/mL medium were selected for the mutagenicity experiment without and with metabolic activation. - Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- 9,10-dimethylbenzanthracene
- ethylmethanesulphonate
- Key result
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity, but tested up to precipitating concentrations
- Remarks:
- Cytotoxicity. in form of decr. rel. survival comp. to the control was noted at conc. 200&400 µg Cresyl-P1/mL medium + and - metabolic act.(4h.exp). Test item precipitation noted macrs.scop. at conc.100 to 400 µg/mL medium in the exp. - and + S9 mix.
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Conclusions:
- Under the present test conditions, Cresyl-P1 tested up to the cytotoxic concentration of 400 µg/mL medium, that led to test item precipitation (4-hour exposure, without and with metabolic activation) was negative in the HPRT-V79 mammalian cell mutagenicity test under conditions where positive controls exerted potent mutagenic effects.
- Executive summary:
The substance was tested in an HPRT-V79 mammalian cell mutagenicity test according to OECD Guideline 476 and under GLP, with and without metabolic activation in Chinese hamster lung fibroblasts. Under the present test conditions, Cresyl-P1 tested up to the cytotoxic concentration of 400 µg/mL medium, that led to test item precipitation (4-hour exposure, without and with metabolic activation) was negative in the HPRT-V79 mammalian cell mutagenicity test under conditions where positive controls exerted potent mutagenic effects.
Referenceopen allclose all
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Justification for classification or non-classification
According to the negative results three valid in vitro tests with the test substance, the substance does not need to be classified according to Regulation (EC) No 1272/2008.
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