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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 246-998-3 | CAS number: 25448-25-3
- 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 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
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 018
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Version / remarks:
- 29st July 2016
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- in vitro mammalian cell gene mutation test using the Hprt and xprt genes
Test material
- Reference substance name:
- Triisotridecyl phosphite
- EC Number:
- 278-758-9
- EC Name:
- Triisotridecyl phosphite
- Cas Number:
- 77745-66-5
- Molecular formula:
- C39H81O3P
- IUPAC Name:
- triisotridecyl phosphite
- Test material form:
- liquid
Constituent 1
- Specific details on test material used for the study:
- NAME OF TEST MATERIAL (as stated in the study report): Trisisotridecylphosphite
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Valtris Specialty Chemicals, Batch No. 330965
- Expiration date of the lot/batch: March 02, 2019
- Purity: 100% (UVCB substance)
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature in original container.
- Stability under test conditions: Phosphites have the potential to hydrolyze in water
- Solubility and stability of the test substance in the solvent/vehicle: Soluble in DMSO at 100 µL/mL.
Method
- Target gene:
- HPRT
Species / strain
- Species / strain / cell type:
- Chinese hamster Ovary (CHO)
- Details on mammalian cell type (if applicable):
- CELLS USED
- Source of cells: Japanese Collection of Research Bioresources
The cell line free from mycoplasma contamination was used in the study. Cultures were free from any contamination during the conduct of the study. CHO-K1 cell line passage number 39 and 38 was used in cytotoxicity test and in main study respectively.
MEDIA USED
α-MEM (Minimum Essential Medium, Eagle α-Modification with nucleosides) with nucleosides (Gupta R.S., 1984) with 10% heat inactivated, sterile, fetal bovine serum was used as the culture medium to grow the CHO-K1 cell line. Culture medium was supplemented with antibiotic and antimycotic solution (Penicillin: 50 IU/mL; Streptomycin: 50 µg/mL and Amphotericin B: 0.25-0.5 μg/mL). At the time of selection Minimum Essential Medium Eagle -modification without nucleosides (-MEM w/o NS) with 10% dialyzed fetal bovine serum was used.
The medium to eliminate the existing mutants in the culture for treatment was prepared by addition of 2 mL of reconstituted HAT supplement to 98 mL of α-MEM w/o NS with 5% fetal bovine serum [50X vial of HAT media supplement was reconstituted using 10 mL of sterile α-MEM w/o NS. The reconstituted supplement contains 5 x 10-5 Hypoxanthine, 2 x 10-5 M Aminopterine and 8 x 10-4 M Thymidine].
- Metabolic activation:
- with and without
- Metabolic activation system:
- rat liver S9 fraction (treated with Aroclor 1254)
- Test concentrations with justification for top dose:
- 0.006, 0.013, 0.025, 0.05, 0.1 and 0.2 µL/mL in the absence and 0.031, 0.063, 0.125, 0.25, 0.5 and 1 µL/mL in the presence of metabolic activation. Based on the results of solubility, precipitation and pH tests, 1 µL/mL was selected as the highest concentration to be tested.
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: solubility testing
Controls
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- benzo(a)pyrene
- ethylmethanesulphonate
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
DURATION
- Exposure duration: 4 hours
- Expression time (cells in growth medium): 7 -9 days
- Selection time (if incubation with a selection agent): 8 days
NUMBER OF REPLICATIONS: 4 flasks for each test concentration
DETERMINATION OF CYTOTOXICITY
- Method: cloning efficiency
- Rationale for test conditions:
- Guidelines and pretest results
- Evaluation criteria:
- Per guidelines
- Statistics:
- Weighted regression analysis was performed to evaluate the dose response relationship (Li, A.P. et al., 1987; Hsie, A.W. et al., 1981) on treatment groups against the negative control group (excluding positive controls).
Results and discussion
Test results
- Species / strain:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- No significant dose-related increase in the mutation frequency was observed in any of the treatment concentrations between 0.006 to 0.2 µL/mL of culture medium in absence or 0.031 to 1 µL/mL of culture medium in presence of metabolic activation (2% v/v S9 mix), and the induced mutation frequencies were comparable to that of the negative control group. All negative controls were within the historical control limits and positive controls showed an increase in the mutant frequency. No relevant influence of the test item on pH value or osmolality was observed in the absence or presence of metabolic activation.
Doses were selected based on a cytotoxicity test.
All criteria for a valid study were met.
Applicant's summary and conclusion
- Conclusions:
- Under these guideline test conditions, it is concluded that trisisotridecylphosphite does not have potential to induce gene mutations at the hprt locus of CHO-K1 cells, in the absence and presence of 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.