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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 201-071-2 | CAS number: 77-94-1
- 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
![](https://chesar.echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vivo
Description of key information
Link to relevant study records
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- chromosome aberration assay
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Route of administration:
- oral: gavage
- Vehicle:
- Vehicle(s)/solvent(s) used: polyethylene glycol
Amount of vehicle (if gavage or dermal): 10 mL/kg bw
Purity: PEG 400 - Duration of treatment / exposure:
- 24 and 48 hours after treatment, the bone marrow cells were collected for chromosome aberration analysis
- Frequency of treatment:
- One single oral treatment
- Post exposure period:
- 24 and 48 hours
- Remarks:
- Doses / Concentrations:
2000 mg/kg bw
Basis:
nominal conc. - No. of animals per sex per dose:
- 10 animals (6 male and 6 female rats, 5 of each sex were evaluated)
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- Cyclophosphamide (CPA)
- Justification for choice of positive control(s): CPA is known to induce a distinct increase in induction of aberration frequency
- Route of administration: Once oral by gavage
- Dose: 15 mg/kg bw - Tissues and cell types examined:
- Bone marrow: at least 100 well spread metaphases per animals were scored for cytogenetic damage
- Evaluation criteria:
- The test item is classified as mutagenic if it induces either a dose-related increase in the number of structural chromosomal aberrations and a reproducible statistically significant positive response for at least one of the test points.
- Statistics:
- non-parametric Mann-Whitney test
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Remarks:
- The mitotic index was slightly reduced after 24 h
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- RESULTS OF RANGE-FINDING STUDY
A single dose was administered at 2000 mg/kg bw to 4 animals (2 males/2 females)
Solubility: Formulated in PEG 400
Clinical signs of toxicity in test animals: Signs recorded 1 - 48 h post-treatment. All animals showed reduction of spontaneous activity at all time points.
Evidence of cytotoxicity in tissue analyzed: The mitotic indices were slightly reduced at 2000 mg/kg bw in the main study indicating that the test item had a slight cytotoxic effect to the bone marrow
Rationale for exposure: 2000 mg/kg bw was the highest dose as required by regulatory Guidelines and expresses the MTD
RESULTS OF DEFINITIVE STUDY
Types of structural aberrations for significant dose levels: No enhancement of the aberrations frequencies
Appropriateness of dose levels and route: The single dose selected of 2000 mg/kg bw was appropriate, as it reflected the MTD and had a slight cytotoxic effect to the bone marrow after 24 h
Statistical evaluation: No significant differences for the test item as compared to the control group - Conclusions:
- Interpretation of results (migrated information): negative
O-Acetyltributyl citrate did not induce chromosomal aberration in the rat in vivo - Executive summary:
A chromosomal aberration study according to OECD 475 was performed in rats in vivo after a single dose of 2000 mg/kg bw O-Acetyltributyl citrate. Five animals per sex and group, i.e. one vehicle control group, two test item groups and one positive control group were employed for the study. The test item was formulated in PEG 400. 24 and 48 h post-treatment, bone marrow cells were collected and 100 well-spread metaphases/animal were scored for chromosomal aberrations. Test item-treated animals showed reduction of spontaneous activity.
The mitotic index was slightly reduced after 24 h, but the test substance did not induce chromosomal aberrations at any time point investigated.
In contrast, the positive control substance induced a highly significant effect documenting the sensitivity of the test system. It can be assumed that the same applies to tributyl citrate (CAS 77-94-1) as it is a near analogue to the test substance acetyl tributyl citrate.
Reference
Table: Experimental results
Experimental group |
Dose |
Preparation hours post administra-tion |
Number of cells scored |
% aberrant cells |
Mean mitotic index (%) |
|
PEG 400 |
0 |
24 |
1000 |
0.3 |
0.3 |
4.87 |
o-Acetytributyl citrate |
2000 |
24 |
1000 |
0.6 |
0.6 |
3.52 |
Cyclophosphamide |
15 |
24 |
1000 |
12.1*** |
11.8*** |
3.09 |
o-Acetytributyl citrate |
2000 |
48 |
1000 |
0.3 |
0.3 |
5.30 |
*** = p<0.0001
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
Genetic toxicity in vitro
There is no study available for this endpoint for the target substance tributyl citrate, therefore data on its structural analogues is taken into account (please refer to the separate read-across statement for further explanation of this procedure):
Acetyltri-2 -ethylhexylcitrate (ATEHC) was tested in the Ames Test for its ability to induce gene mutations in the plate incorporation test (experiment I) and in the preincubation test (experiment II) with Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 (Hamann, 2000; GLP study according to OECD 471 and EU method B.14). The test item was tested in two independent experiments at several concentrations. Each assay was conducted with and without metabolic activation (S9 mix). The concentrations, including the controls, were tested in triplicate. The following concentrations of the test item were prepared and used in the experiments: 100.0, 316.2, 1000, 2000, 3000 and 4000 µg/plate. Slight toxic effects of the test item (indicated by a reduction of the spontaneous rate) were observed at the highest investigated dose without metabolic activation in the tester strains TA 100 (2nd experiment) and TA 1537 (1st experiment). No substantial increases in the revertant colony numbers of any of the five test strains were detected at any dose level of the test item neither with or without metabolic activation in both independently performed experiments. Therefore, the test item is considered to be non-mutagenic in this bacterial reverse mutation assay. As positive controls reference mutagens were tested in parallel to the test item. They showed a distinct increase of induced revertant colonies. It can be assumed that the same applies to tributyl citrate (CAS 77-94-1) as it is a near analogue to the test substance acetyltri-2 -ethylhexylcitrate (ATEHC).
ATBC did not induce mutations in the Mouse Lymphoma Assay (L5178Y TK +/-) with and without metabolic activation (Bigger and Harbell, 1991; cited in US EPA (2003) HPV Chemicals Challenge Program). The test has been carried out according to OECD Guideline 476.
Taking all these result into account, it can be concluded that tributyl citrate is not mutagenic.
Genetic toxicity in vivo
A chromosomal aberration study according to OECD 475 was performed in rats in vivo after a single dose of 2000 mg/kg bw O-Acetyltributyl citrate (Bigger and Harbell, 1991). Five animals per sex and group, i.e. one vehicle control group, two test item groups and one positive control group were employed for the study. The test item was formulated in PEG 400. 24 and 48 h post-treatment, bone marrow cells were collected and 100 well-spread metaphases/animal were scored for chromosomal aberrations. Test item-treated animals showed reduction of spontaneous activity.
The mitotic index was slightly reduced after 24 h, but the test substance did not induce chromosomal aberrations at any time point investigated.
In contrast, the positive control substance induced a highly significant effect documenting the sensitivity of the test system.
Justification for selection of genetic toxicity endpoint
GLP and guideline study conducted on mammalian cells with the structural analogue ATBC.
Justification for classification or non-classification
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.
![ECHA](/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/echa_logo.png)