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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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
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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
Link to relevant study record(s)
- Endpoint:
- basic toxicokinetics in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Objective of study:
- metabolism
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- In vitro metabolism in rat serum, liver and intestinal homogenates, with rates of hydrolysis
- GLP compliance:
- no
- Radiolabelling:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Route of administration:
- other: in vitro
- Preliminary studies:
- Ester hydrolysis did not take place when the test material was added to biological media directly without a solvent. Rapid hydrolysis was achieved when test material was added in a solution in DMSO.
- Type:
- metabolism
- Results:
- Hydrolysis by carboxyesterases
- Details on absorption:
- Low, due to lipophilic nature of the test substance. No hydrolysis was noted in the absence of solvent, indicating that bioavailability is very low.
- Metabolites identified:
- yes
- Details on metabolites:
- Hydrolysis occurred upon incubation with rat serum, liver and intestinal enzyme preparations, with iberation of hexanol, initially 1 mole per mole of parent compound. Mass spectroscopy identified initial formation of dihyhexyl citrate. The generation of the diester, monoester and product (citrate plus hexanol) was 0.02 h, when the concentration was 50 nmol/ml of medium. Hydrolysis as measured by generation of hexanol is 5 times faster in serum than in liver, and is slowest in intestinal preparations. Rate of hydrolysis is concentration dependent, with faster breakdown at lower concentrations than at higher. Hydrolysis of the hexyl moiety was faster than hydrolysis of the acetyl or butyryl moieties in analogue substances.
In rat liver, the half lives of ester hydrolysis and hexanol formation was 6 and 0.04 h. This is slower than in serum.
Hexanol was found to be stable during incubation with rat serum for 8 h, not showing further oxidation. Incubation of hexanol in rat liver cytosolic fraction indicated that this alcohol undergoes enzymatic modification, with half lives of 2.7, 3 and 56 hours at concentrations of 50, 150 and 3000 nmol/ml. No identification of products was presented.
Hydrolysis of the hexyl moiety is faster than that of the acetyl moiety on the citrate portion of the molecule. No hexyl citrate was formed during incubation of acetyl trihexyl citrate. - Bioaccessibility (or Bioavailability) testing results:
- The substance is not highly bioavailable due to low water solubility and high lipophilicity.
- Conclusions:
- The in vitro hydrolysis of the test material was investigated in preparations of rat serum, liver homogenate and intestinal homogenate. The half-life of the substance was 0.02 h (at 50 nmol/ml serum), and relatively fastest in serum which is rich in carboxyesterases. The breakdown initially formed acetyl dihexyl citrate and hexanol, the latter of which was stable for 8 h in serum. Hydrolysis was slower in rat liver, at 0.3 h. Bioavailability in vivo is expected to be low, due to the low water solubility and high lipophilicity of the substance; DMSO solvent was needed to solubilize the material for this in vitro experiment.
Reference
Description of key information
Limited bioavailability; rapid metabolism by esterases.
Key value for chemical safety assessment
- Bioaccumulation potential:
- low bioaccumulation potential
- Absorption rate - oral (%):
- 50
- Absorption rate - dermal (%):
- 10
- Absorption rate - inhalation (%):
- 10
Additional information
Molecular weight 487 (< 1000)
Water solubility: insoluble, 0.0006 mg/L (est).
Log Kow: 7.23 (est).
Lipinski Rule of 5: 1 violation
Fouda, 1982: Not bioavailable in biological fluids (serum, liver homogenate or intestinal cell homogenate) without a solvent (DMSO). Potentially soluble as micelles with bile fluids. No significant oral toxicity observed in acute and subchronic studies.
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.
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