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EC number: - | 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
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
Not mutagenic or genotoxic.
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 2002
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Justification for type of information:
- Judged to be scientifically reliable and appropriate for risk assessment by the Expert Panel of dermatologists and scientists at the Cosmetics Ingredient Review, Washington, DC., U.S.A.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Principles of method if other than guideline:
- OECD guideline method by GLP
- GLP compliance:
- not specified
- Type of assay:
- in vitro mammalian cell gene mutation tests using the thymidine kinase gene
- Target gene:
- TK
- Species / strain / cell type:
- mouse lymphoma L5178Y cells
- Additional strain / cell type characteristics:
- not specified
- Metabolic activation:
- with and without
- Test concentrations with justification for top dose:
- concentrations ranged from 6 to 46 µg/ml (with and without metabolic activation)
- Vehicle / solvent:
- not specified
- Untreated negative controls:
- not specified
- Negative solvent / vehicle controls:
- not specified
- True negative controls:
- not specified
- Positive controls:
- yes
- Positive control substance:
- 3-methylcholanthrene
- ethylmethanesulphonate
- Details on test system and experimental conditions:
- Three experimental traisl were included. Mouse lymphoma cells were tested with and without metabolic activation.
- Key result
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- valid
- Conclusions:
- The test material was reported by an expert panel for the U.S. Cosmetic Ingredient Review to be nonmutagenic in the mouse lymphoma gene mutation assay (MLA).
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: experimental result in a reputable laboratory; precedes establishment of guidelines and GLP
- Justification for type of information:
-
An analogue approach is used for the hazard assessment of several human health endpoints. The hypothesis for the analogue approach is that data can be read-across from data-rich substances, namely acetyl tributyl citrate (ATBC, CAS 77-90-7), acetyl triethyl citrate (CAS 77-89-4) and triethyl citrate (TEC, CAS 77-93-0) to acetyl trihexyl citrate (ATHC, CAS 24817-92-3). The analogue approach is based on common breakdown products via physical and biological processes, and similar functional groups, according to Annex XI, Section 1.5, of Regulation EC No. 1907/2006. Read-across to ATHC is indicated in order to avoid unnecessary in vivo testing according to Article 25 of Regulation EC No. 1907/2006.
The analogue approach to evaluating the safety of triethyl citrate is adopted here, reflecting the approach used by various expert panels and authoritative bodies in their safety assessment of TEC, included JECFA, EFSA, U.S. FDA, EPA and CIR. The use of analogues for hazard evaluation is justified (Scenarios 1 and 2 of the RAAF, 2015) because the substances have common breakdown products via physical and biological processes, which reflects the similar functional groups in their chemical structure. The proposed analogues have similar functional groups, including: a citric acid (tricarboxylic acid) backbone, three short-chain alkyl esters, and an acetyl group (except for TEC). Other than the acetyl group, there are no other functional groups which may introduce additional toxicities. The substances display similar classification based on similar toxicities.
The target substance is expected to have essentially the same effect in the toxicity test/endpoint as does the source substance. Dose descriptors obtained for derivation of a DNEL are adequate and appropriate, and do not underestimate the hazards of the registered substance.
This information is adequate to fulfill the data requirements of Annex IX, to be the basis for classification and labelling decisions, and for risk assessment. - Reason / purpose for cross-reference:
- read-across source
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Principles of method if other than guideline:
- standard Ames assay method with S9 fractions from additional species
- GLP compliance:
- no
- Remarks:
- precedes establishment of GLP
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- histidine
- Species / strain / cell type:
- S. typhimurium TA 1535
- Species / strain / cell type:
- S. typhimurium TA 1537
- Species / strain / cell type:
- S. typhimurium TA 1538
- Species / strain / cell type:
- Saccharomyces cerevisiae
- Details on mammalian cell type (if applicable):
- strain D4
- Metabolic activation:
- with and without
- Metabolic activation system:
- rat, mouse and monkey S-9 liver fraction
- Test concentrations with justification for top dose:
- 0.4 to 1.7%
- Vehicle / solvent:
- not specified
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- not specified
- True negative controls:
- not specified
- Positive controls:
- not specified
- Positive control substance:
- not specified
- Details on test system and experimental conditions:
- Two types of assays were performed, i.e. plate tests and suspension tests. Based on cell toxicity studies, concentrations from 0.4 to 1.7% were used as the dose levels in the mutagenicity tests.
- Key result
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not valid
- Positive controls validity:
- not specified
- Key result
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not valid
- Positive controls validity:
- not specified
- Key result
- Species / strain:
- S. typhimurium TA 1538
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not valid
- Positive controls validity:
- not specified
- Key result
- Species / strain:
- Saccharomyces cerevisiae
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not valid
- Positive controls validity:
- not specified
- Remarks on result:
- other: negative
- Remarks:
- Not mutagenic
- Conclusions:
- The results are negative, non-mutagenic.
The analogue triethyl citrate was tested in a reverse bacterial mutatation assay using Salmonella typhimurium strains 1535, 1537 and 1538, and Saccharomyces cervisiae D4, with and without S-9 liver fractions (metabolic activation) from rat, mouse and monkey. All results were negative (non-mutagenic). These data are applicable to the target substance, and are adequate for risk assessment and classification and labelling. - Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Evaluated as reliable by several authoritative bodies, such as JECFA, EFSA, CSTEE, U.S. Environmental Protection Agency, Cosmetic Ingredient Review Panel, etc.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- GLP compliance:
- yes
- Type of assay:
- in vitro mammalian chromosome aberration test
- Target gene:
- none. whole chromosomes
- Species / strain / cell type:
- lymphocytes: rat
- Metabolic activation:
- with and without
- Metabolic activation system:
- rat liver S9
- Test concentrations with justification for top dose:
- not specified
- Vehicle / solvent:
- not specified
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- not specified
- True negative controls:
- not specified
- Positive controls:
- not specified
- Positive control substance:
- not specified
- Remarks:
- Assume all appropriate controls included in this guideline study.
- Details on test system and experimental conditions:
- Cultures were initiated by inoculating approximately 0.3 ml of whole blood/5 ml of culture medium. Cultures were set up in duplicate at each dose level and incubated at 37°C. Forty-eight hours after setting up of whole blood cultures, the rat lymphocytes were treated with the test substance for four hours at concentrations of 0 (negative control), 4, 13.3, 40, 133 and 400 µg/ml both with and without S-9 metabolic activation. S-9 liver homogenate prepared from Aroclor 1254-teated Sprague-Dawley rats was purchased from an outside vendor. S-9 mix was prepared fresh and used on the day of preparation. DMSO was used to dissolve the test substance and also was used as the negative control group substance. The final concentration of DMSO in the culture medium was 1%. Cultures treated with 1000 µg/ml ethyl methanesulfonate and 4.2 µg/ml cyclophosphamide were used as positive controls for the non-activation and activation assays, respectively. The cultures were harvested 24 hours after termination of treatment. Mitotic indices were determined as the number of cells in metaphase among 1000 cells/replicate and expressed as percentages. Based upon the data on mitotic indices, cultures treated with the test substance at concentrations of 50, 133 and 400 µg/ml were selected for determining the frequencies of chromosomal aberrations. A total of 100 cells were scored in each replicate in the treated and negative control cultures and 50 cells were scored in the positive control cultures. Only those metaphases that contained 42 chromosomes were scored with the exception of severely damaged cells (cells having ≥10 aberrations/cell), in which case, accurate counts of the chromosomes were not possible. Gaps were not included in calculations of total cytogenetic aberrations. The following aberrations were included in the evaluation: chromatid breaks, chromatid exchanges, chromosome breaks, and chromosome exchanges.
- Statistics:
- yes, no information on methods
- Key result
- Species / strain:
- lymphocytes: rat
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Additional information on results:
- The test substance showed no evidence of mutagenic activity in the presence and absence of an S-9 metabolic activation system.
- Remarks on result:
- other: negative
- Remarks:
- non-clastogenic
- Conclusions:
- The test was negative for induction of genotoxicity.
An analogue substance, acetyl tributyl citrate, showed no evidence of clastogenic activity in the presence and absence of an S-9 metabolic activation system in cultured rat lymphocytes. Data can be read-across between the analogues and target substance based on common breakdown products. This is adequate to fulfill the information requirements, to be the basis for classification and labelling decisions, and for risk assessment.
Referenceopen allclose all
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Description of key information
No studies required
Mode of Action Analysis / Human Relevance Framework
Not applicable
Additional information
Justification for classification or non-classification
There is no evidence of mutagenicity or clastogenicity in studies of analogues of the registered substance. The substance is not classified according to Regulation EC. No. 1272/2008.
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.