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EC number: 208-686-5 | CAS number: 538-23-8
- 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:
- supporting 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:
- Blood D-(–)-3-Hydroxybutyrate Concentrations after Oral Administration of Trioctanoin, Trinonanoin, or Tridecanoin to Newborn Rhesus Monkeys (Macaca mulatta)
- Author:
- Tetrick, M.A., Greer, F.R. and Benevenga N.J.
- Year:
- 2 010
- Bibliographic source:
- Comperative Medicine 2010 Dec;60(6):486-90
Materials and methods
- Objective of study:
- absorption
- Principles of method if other than guideline:
- 4 groups of 5 newborn monkeys were given a single dose of water or medium-chain triglycerides by nasogastric tube. The dose provided approximately 80% of the expected energy requirement. Plasma C8:0, C9:0, and C10:0 fatty acids and whole-blood D-(–)-3-hydroxybutyrate (3HB) concentrations were measured at 0, 1, and 3 h after dosing.
- GLP compliance:
- not specified
Test material
- Reference substance name:
- Glycerol trioctanoate
- EC Number:
- 208-686-5
- EC Name:
- Glycerol trioctanoate
- Cas Number:
- 538-23-8
- Molecular formula:
- C27H50O6
- IUPAC Name:
- 1,3-bis(octanoyloxy)propan-2-yl octanoate
Constituent 1
- Radiolabelling:
- no
Test animals
- Species:
- monkey
- Strain:
- other: Macaca mulatta
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Wisconsin National Primate Research Center
- Age at study initiation: 15 h
- Weight at study initiation: mean ca. 530 g
- Housing: the infants were held in a relatively quiet location, provided with a blanket to cling to and a heat lamp. Infants were excluded from this study if the primate center staff judged them to be at risk of maternal rejection after the 3- to 5-h separation needed for the evaluation.
- Diet: Monkey diet 5037/5038, PMI Nutrition International, St Louis, MO, USA, ad libitum, supplemented with fresh fruit 2 to 3 times per week
- Water: ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 °C
- Photoperiod (hrs dark / hrs light): 12 / 12
Administration / exposure
- Route of administration:
- other: nasogastric tube
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
The dosage was calculated to provide approximately 272 kJ gross energy per kilogram or 136 kJ for a 500-g newborn rhesus monkey, based on a basal energy requirement of: (292 kJ W^(0.75)) × (0.5 kg body wt)^0.75 = 174 kJ.
The dose was estimated to provide approximately 80% (135 of 174 kJ) of the rhesus infants’ daily basal energy requirement. - Duration and frequency of treatment / exposure:
- Single administration on day 0 (newborn)
Doses / concentrations
- Dose / conc.:
- 8.1 other: mg/kg bw (actual dose received)
- Remarks:
- 8.4 mL/kg bw; single dose
- No. of animals per sex per dose / concentration:
- 5
- Control animals:
- yes, sham-exposed
- Details on study design:
- - Dose selection rationale: The dose was estimated to provide approximately 80% (135 of 174 kJ) of the rhesus infants’ daily basal energy requirement. Estimation of resting energy expenditure was based on observations with newborn piglets, approximately 293 kJ/ (kg × d)17 according to expired CO2 (367 μmol/[min×kg]0.75)23 and an assumed respiratory quotient of 0.86. Use of 80% of the basal energy requirement was judged to be a sufficient amount to have an effect, based on previous work with energy metabolism in newborn piglets and their response to medium-chain triglycerides.
- Other: Treatments included also oral doses of Trinonanoin (C9:0) or water control. An additional group of 5 monkeys became available later and was treated with the Tridecanoin (C10:0). - Details on dosing and sampling:
- METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled: blood (1 mL)
- Time and frequency of sampling: before dosing (0 h), 1 and 3 hours after administration
- From how many animals: all 5 animals, not pooled
- Method type(s) for identification: Fatty acid quantitation by HPLC, D-(–)-3-Hydroxybutyrate (3HB) analysis by dye-linked spectrophotometric
method
- Limits of detection and quantification: The 3HB detection limit in the 0.5 mL blood sample by using this assay was 3 to 5 μM.
- Other: [3-14C]3HB and [1-14C]nonanoic acid were added to sample to allow to correct for recovery - Statistics:
- Plasma fatty acid and blood 3HB concentrations from groups of newborn rhesus monkeys were analyzed by one-way ANOVA by using a General Linear Models procedure of Statistical Analysis System release 6.09 (SAS Institute, Cary, NC). The split-plot model included the main effect of oral dose, with time and time×treatment interaction as a subplot. Inferences regarding oral dose were based on nonorthogonal contrasts based on perceived biologic importance. Nonorthogonal contrasts were used to compare plasma fatty acid concentrations due to treatment: water versus 8:0, 8:0 versus 9:0, and 9:0 versus 10:0. Orthogonal contrasts were used to compare the group mean 3HB concentrations: water-treated group to MCT treatments, 8:0 versus 9:0, 8:0 versus 10:0, and 9:0 versus 10:0. Fatty acid and 3HB concentrations at 0 versus 1 h, 0 versus 3 h, and 1 versus 3 h were compared for each treatment by using orthogonal contrasts. Outlier values were defined as individual values falling outside a range of 2 SD on either side of the mean for the other animals in the group.
Results and discussion
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- Plasma concentrations of free fatty acids (C8, C9, or C10) and ketone (3HB) increased with time after the dose. At 1 and 3 h, concentrations of C8 and C9 did not differ, but C9 was greater than C10. At 1 h, blood 3HB concentrations due to C8 triglyceride administration were higher than C9 or C10 (503 versus 174 and 225 μmol/L respectively). As chain length increased from C8 to C10, blood concentration of 3HB decreased.
Metabolite characterisation studies
- Metabolites identified:
- yes
- Details on metabolites:
- C8:0 fatty acid, 3-hydroxybutyrate
Any other information on results incl. tables
Clinical observations:
Newborn monkeys dosed with MCT remained alert and active after dosage. No episodes of narcolepsy were noted.
Plasma fatty acid and whole-blood 3HB concentrations (μM , mean ± SEM):
Treatment Group | Metabolite measured | Concentration (µm) at | ||
0 h | 1 h | 3 h | ||
water | C8:0 | 30 ± 8 | 29 ± 8f | 64 ± 28 |
C8 | C8:0 | 21 ± 17d | 117 ± 28e,g | 128 ± 8e |
C9 | C9:0 | not detected d | 154 ± 19e,h | 207 ± 60e,f |
C10a | C10:0 | 4 ± 1d | 76 ± 27e,g | 83 ± 9e,g |
water | 3HBb | 69 ± 36d, f | 50 ± 16d,f | 112 ± 53d,f |
C8 | 3HB | 130 ± 25d,g | 503 ± 113e,g | 585 ± 111e,g |
C9 | 3HB | 48 ± 12d,f | 174 ± 42e,h | 268 ± 62e,h |
C10c | 3HB | 46 ± 16d,f | 225 ± 150d,h | 282 ± 177d,h |
All treatment groups contained 5 macaques, except for C10 groups, which contained 4 monkeys each due to elimination of an outlier.
a: Concentrations (μM, mean±SEM) with outlier included were: 0 h, 13±1; 1 h, 119±47; and 3 h, 107±25.
b: Due to significant (P<0.05) treatment x time interaction, all treatment comparisons for 3HB were made within time point.
c: Concentrations (μM, mean±SEM) with outlier included were: 0 h, 163±117; 1 h, 463±265; and 3 h, 710±449.
d,e: Values that differ (P<0.05) within treatment groups (rows) are indicated by different superscript letters.
f,g,h: Values that differ (P<0.05) within time points (columns) are indicated by different superscript letters.
Applicant's summary and conclusion
- Conclusions:
- After single nasogastric administration of glycerol trioctanoate to monkeys at a dose of 8.1 mg/kg bw, the metabolites octanoic acid and 3-hydroxybutyrate were detectable at higher concentrations in blood, which had been sampled 1 and 3 hours after administration as compared to levels in blood sampled prior to administration. Due to the observed metabolism in monkeys, no bioaccumulation potential is expected for glycerol trioctanoate.
- Executive summary:
Administration of C8 triglyceride lead to higher plasma concentrations of the respective hydrolysis products (free fatty acid) than after administration of C9 or C10 triglyceride.
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