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Diss Factsheets
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EC number: 201-066-5 | CAS number: 77-89-4
- 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
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics in 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
Data source
Reference
- Reference Type:
- publication
- Title:
- Pharmacokinetics and Metabolism of Acetyl Triethyl Citrate, aWater-Soluble Plasticizer for Pharmaceutical Polymers in Rats
- Author:
- Kim H, Ji YS, Rehman SU, Choi MS, Gye MC, Yoo HH.
- Year:
- 2 019
- Bibliographic source:
- Pharmaceutics 11(4): 162; doi:10.3390/pharmaceutics11040162
Materials and methods
- Objective of study:
- metabolism
- toxicokinetics
- GLP compliance:
- not specified
- Remarks:
- Data from Korea and not performed for REACH registration, GLP is not specified in the publication
Test material
- Reference substance name:
- Triethyl O-acetylcitrate
- EC Number:
- 201-066-5
- EC Name:
- Triethyl O-acetylcitrate
- Cas Number:
- 77-89-4
- Molecular formula:
- C14H22O8
- IUPAC Name:
- triethyl 2-acetoxypropane-1,2,3-tricarboxylate
- Details on test material:
- ATEC purchased from Sigma-Aldrich St. Louis, MO, USA
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Orient Bio (Seongnam, Korea)
- Age at study initiation: 8 weeks
- Weight at study initiation: approximately 250–290 g
- Housing: not reported
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: not reported
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 +/- 3
- Humidity (%): 55 +/- 15
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12
- Fasting period : 12 h
Administration / exposure
- Route of administration:
- other: oral and i.v.
- Vehicle:
- polyethylene glycol
- Details on exposure:
- 30% poly-ethylene glycol (PEG) at a concentration of 10 mg/mL for intravenous (i.v.) administration and 500 mg/mL for oral (p.o.)
Doses / concentrationsopen allclose all
- Dose / conc.:
- 10 mg/kg bw/day (nominal)
- Remarks:
- i.v.
- Dose / conc.:
- 500 mg/kg bw/day (nominal)
- Remarks:
- p.o.
- No. of animals per sex per dose / concentration:
- 6
- Control animals:
- no
- Details on dosing and sampling:
- Blood samples (200 µL) were collected from the carotid artery in tubes containing 1 µL of heparin (5000 IU) and 5 µL of an esterase inhibitor, PMSF (1M). The collection time points were 1 min, 2 min, 5 min, 10 min, 15 min, 30 min, 1 h, 2 h, 4 h, 6 h, 10 h, and 24 h after the i.v. injection and 5 min, 15 min, 30 m, 45 min, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 24 h, and 36 h after p.o. administration. The collected blood samples were
centrifuged at 10,000x g and 4 °C for 5 min, and the supernatant plasma was collected.
To determine the metabolic profile of ATEC, the rats were placed in metabolic cages for 5 days after oral dosing (500 mg/kg). Urine and feces were collected 10 h, 1 day, 2 day, 3 day, 4 day, and 4.3 day after oral administration.
Results and discussion
Main ADME results
- Type:
- clearance
- Results:
- Cl (L/h/kg): i.v. 125.1; p.o. 145.5
Toxicokinetic / pharmacokinetic studies
- Details on excretion:
- After i.v. administration, ATEC was rapidly eliminated with a terminal half-life of 0.03 and mean residence time of 0.03 h, whereas oral administration of ATEC resulted in 1.03 h of terminal half-life and a mean residence time of 6.56 h. Longer terminal half-life and residence time were observed after oral administration than intravenous injection.
Toxicokinetic parametersopen allclose all
- Test no.:
- #1
- Toxicokinetic parameters:
- AUC: 78.1
- Remarks:
- i.v.
- Test no.:
- #2
- Toxicokinetic parameters:
- AUC: 529.6
- Remarks:
- p.o.
- Test no.:
- #1
- Toxicokinetic parameters:
- Cmax: 1219.6
- Remarks:
- i.v.
- Test no.:
- #2
- Toxicokinetic parameters:
- Cmax: 444.5
- Remarks:
- p.o.
- Test no.:
- #1
- Toxicokinetic parameters:
- half-life 1st: 0.03
- Remarks:
- i.v.
- Test no.:
- #2
- Toxicokinetic parameters:
- half-life 1st: 1.03
- Remarks:
- p.o.
Metabolite characterisation studies
- Metabolites identified:
- yes
- Details on metabolites:
- The LC-QTOF MS analysis of plasma, urine and feces samples showed that ATEC was extensively metabolized and excreted mainly as metabolites rather than as the parent.
Acetyl diethyl citrate and diethyl citrate were the major metabolites of ATEC. Unchanged ATEC was mostly excreted within 24 h after the administration of the dose, but acetyl diethyl citrate and diethyl citrate were excreted up to 4 days after the dose.
Bioaccessibility (or Bioavailability)
- Bioaccessibility (or Bioavailability) testing results:
- The absolute bioavailability (F) of ATEC was 14.8% (as calculated by the dose-corrected AUC p.o. divided by the AUC i.v.). This relatively low F value pointed to poor absorption of ATEC from the gastrointestinal tract, degradation of ATEC in the gut, and extensive first-pass effects. After i.v. administration,
Applicant's summary and conclusion
- Conclusions:
- The pharmacokinetic study showed that ATEC rapidly disappeared from plasma. The metabolite profiling data indicated that ATEC was extensively metabolized and excreted mainly as metabolites rather than as the parent form.
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