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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 911-915-8 | CAS number: -
- 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 cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2002-01-07 to 2002-01-18
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 002
- Report date:
- 2002
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Deviations:
- no
- Principles of method if other than guideline:
- not applicable
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- in vitro mammalian chromosome aberration test
Test material
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Lot/batch No.of test material: 960
- Expiration date of the lot/batch: 2002-04
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature
Method
- Target gene:
- not applicable
Species / strain
- Species / strain / cell type:
- mammalian cell line, other: human peripheral lymphocytes
- Details on mammalian cell type (if applicable):
- human peripheral lymphocytes
- Additional strain / cell type characteristics:
- not specified
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 mix
- Test concentrations with justification for top dose:
- Preliminary study (Cytotoxicity study):
- without (24h exposure) and with (4h exposure) metabolic activation:
10, 25, 100, 250, 1000, 2500 and 5000 ug Olaflur/mL medium
Main Study
- without metabolic activation (4 h and 24h exposure):
1.25, 2.5, 5, 10 ug Olaflur/mL medium
- with metabolic activation (4h exposure):
2.5, 5, 10, 20 ug Olaflur/mL medium - Vehicle / solvent:
- Olaflur was dissolved and diluted to the appropriate concentrations in aqua ad iniectabilia prior to the treatment of the cells. Aqua ad iniectabilia served as the negative control substance.
Controlsopen allclose all
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Remarks:
- aqua ad iniectabilia
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- Remarks:
- with metabolic activation (S9 mix)
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Remarks:
- aqua ad iniectabilia
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- mitomycin C
- Remarks:
- without metabolic activation (S9 mix)
- Details on test system and experimental conditions:
- Culture establishment
Human peripheral blood was obtained by venipuncture from healthy donors known to be without any medication and collected in heparinised vessels. Small inocula of whole blood (0.5 mL) were added to tubes containing 5 mL of complete culture medium. The tubes were sealed and incubated at 37°C with occasional shaking to prevent clumping.
Study performance
The test samples of Olaflur were assayed in cultures both in the presence and absence of metabolic activation by rat liver post-mitochondrial fraction (S9 mix) from Aroclor-1254 induced animals. Aqua ad iniectabilia served as the vehicle.
The test was carried out employing 2 exposure times without S9 mix: 4 and 24 hours, and 1 exposure time with S9 mix: 4 hours. Harvesting time was 25 hours after start of exposure. The incubation procedure took place in the dark.
The study was conducted in duplicate; the duplicate cultures being derived from different donors.
The concentrations employed were chosen based on the results of a cytotoxicity study.
Culture harvesting
Two hours before termination cell division was arrested by addition of colcemid; after further 2h-incubation the cells were harvested (80 – 100xg), pellets of cells treated according to guideline and slides prepared for evaluation. - Evaluation criteria:
- For each treatment and culture 100 metaphases/ plate were examined. Observed aberrations were noted and scored according to J.R.K. Savage (1975).
Metaphases which differed from the normal diploid complement were excluded from evaluation. However, substance-related variations of the normal chromosome number were noted (polyploidy). For examination of the toxicity of Olaflur 1000 cells were scored and the mitotic index was calculated as the percentage of cells in metaphase. - Statistics:
- Statistical evaluation by comparison of the number of chromosome aberrations of samples and solvent control by using the exact test of R.A. Fisher (p<= 0.05). Only total numbers of cells with aberrations were analysed - chromatid gaps were exempted as no true chromosomal aberration.
Results and discussion
Test results
- Key result
- Species / strain:
- mammalian cell line, other: human peripheral lymphocytes
- Metabolic activation:
- with and without
- Genotoxicity:
- not specified
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- Cytotoxicity investigated in a preliminary study. Based on these results the concentrations for the main study were selected
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- no data
- Remarks on result:
- other: all strains/cell types tested
Any other information on results incl. tables
no remarks
Applicant's summary and conclusion
- Conclusions:
- Under the present test conditions Olaflur tested up to cytotoxic concentrations in the absence and 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 damage.
- Executive summary:
The test samples of Olaflur were assayed in an in vitro cytogenetic study using human lymphocyte cultures both in the presence and absence of metabolic activation by rat liver post-mitochondrial fraction (S9 mix) from Aroclor-1254 induced animals. Aqua ad iniectabilia served as the vehicle.
The test was carried out employing 2 exposure times without S9 mix: 4 and 24 hours, and 1 exposure time with S9 mix: 4 hours. Harvesting time was 25 hours after start of exposure. The incubation procedure took place in the dark. The study was conducted in duplicate.
The concentrations employed were chosen based on the results of a cytotoxicity study.
In this preliminary experiment, a pronounced cytotoxicity was noted at the concentration of 10 ug Olaflur/mL medium in the experiment without metabolic activation (24h exposure), a complete cytotoxicity started at 25 ug Olaflur/mL medium.
A pronounced cytotoxicity was noted at a concentration of 25 ug Olaflur/mL medium in the experiment with metabolic activation (4h exposure), a complete cytotoxicity started at a concentration of 100 ug Olaflur /mL medium.
Main Study Concentrations
Hence, the top concentrations employed in the main study were 10 ug Olaflur/mL medium in the experiment without and 20 ug Olaflur/mL medium in the experiment with metabolic activation (4h and 24h exposure, respectively).
Positive Controls
Mitomycin C and cyclophosphamide were employed as positive control chemicals in the absence and presence of metabolic activation, respectively.
Tests without metabolic activation (4h and 24h exposure)
The mean incidence of chromosomal aberrations (excluding gaps) of the cells treated with Olaflur at concentrations of 1.25, 2.5, 5 of 10 ug Olaflur/mL medium in the absence of metabolic activation ranged from 1.5 % to 3.0 % in the two independent experiments with blood from different donors.
The top concentration of 10 ug Olaflur/mL medium (mitotic index: 0.13) caused a pronounced cytotoxicity after the 24h exposure, exceeding the toxicity range recommended in the respective guidelines for 24h exposure.
Only at the pronounced cytotoxic concentration of 10 ug Olaflur/mL medium a marginal, though not significant, increase was noted in the number of aberrations to 5.4 %, exceeding slightly the toxicity control range.
It is known that high cytotoxicity causes artefacts in form of aberrations in in vitro chromosomal tests. Hence, the increase at the concentration of 10 ug Olaflur/mL medium at 24h only and obtained at very high cytotoxicity is considered as artefact and not test substance-related.
All other results obtained are considered to be within the normal range of the negative control where a mean incidence of chromosomal aberrations (excluding gaps) of 1.5 or 1.0% was observed after a 4 h or 24 h exposure.
Test with metabolic activation (4 h exposure)
The mean incidence of chromosomal aberrations (excluding gaps) of the cells treated with Olaflur (2.5, 5, 10 or 20 ug Olaflur/mL medium) in the presence of metabolic activation ranged from 0.0 % to 3.0 % in the two independent experiments.
The concentrations of 10 or 20 ug Olaflur/mL medium (mitotic indices: 0.82 and 0.14, respectively) caused a pronounced cytotoxicity after the 4h exposure. The results obtained are considered to be within the normal range of the negative control where the incidence of chromosomal aberrations (excluding gaps) ranged from 0.0% to 5.0 % for the last 30 experiments. In the same test, mitomycin C and cyclophosphamide induced significant damage.
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.