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EC number: 204-791-5 | CAS number: 126-53-4
- 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
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Endpoint summary
Administrative data
Link to relevant study record(s)
- Endpoint:
- basic toxicokinetics in vivo
- 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: Well documented study, meets generally accepted scientific principles, acceptable for assessment.
- Objective of study:
- absorption
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- The mechanism of the intestinal fat absorption has been studied with 14C labeled fat in rats with the intestinal lymph duct cannulated.
- GLP compliance:
- no
- Radiolabelling:
- yes
- Remarks:
- 14C labeled fat
- Species:
- rat
- Strain:
- not specified
- Sex:
- not specified
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Duration and frequency of treatment / exposure:
- single oral exposure
(at least 18 hours after surgery) - Remarks:
- Doses / Concentrations:
A) 0.5 mL corn oil + 2.5 mg active palmitic acid-1-14C
B) 0.5 mL corn oil transesterified with 2.5 mg active palmitic acid-1-14C
C) 0.5 mL hydrolysed corn oil + 2.5 mg active palmitic acid-1-14C - No. of animals per sex per dose / concentration:
- 5-6
- Control animals:
- no
- Details on absorption:
- 24 hours after administration of the different fats the mean recovered activities in lymph were as following:
A) 0.5 mL corn oil + 2.5 mg active palmitic acid-1-14C: 57.0 %
B) 0.5 mL corn oil transesterified with 2.5 mg active palmitic acid-1-14C: 61.7 %
C) 0.5 mL hydrolysed corn oil + 2.5 mg active palmitic acid-1-14C: 62.3 %
In all three groups of experiments maximum recoveries were found after 24 hours, i.e. 80.9, 85.0 and 87.5 % of the activity given.
Free fatty acids administered alone or together with glycerides appear in the lymph in glycerides and phospholipids.
No free fatty acids or soaps appear in the lymph.
The intestinal wall supplies a quantitatively important part of phospholipids to the blood during fat absorption.
The recoveries in the lymph of the fat fed varied widely. Diarrhea occured in some animals especially after feeding hydrolysed corn oil. - Details on distribution in tissues:
- Absorbed fat is mainly transported via lymphatic channels to the systemic circulation whether fed as glycerides or as fatty acids.
- Details on metabolites:
- A complete hydrolysis of the fat in the intestinal lumen might occur in the rat.
- Conclusions:
- Interpretation of results (migrated information): low bioaccumulation potential based on study results
Mean absorption rate of corn oil combined with palmitic acid was between 57 - 62 %. - Executive summary:
The mechanism of the intestinal fat absorption has been studied with C14 labelled fat in rats with the intestinal lymph duct cannulated.
It has been found that:
1. Absorbed fat is mainly transported via lymphatic channels to the systemic circulation whether fed as glycerides or as free fatty acids
2. Free fatty acids administered alone or together with the glycerides appear in the lymph in glycerides and phospholipids. No free fatty acids or soaps appear in the lymph.
3. The intestinal wall supplies a quantitatively important part of phospholipids to the blood during fat absorption.
4. A complete hydrolysis of the fat in the intestinal lumen might occur in the rat.
- Endpoint:
- basic toxicokinetics in vitro / ex vivo
- 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: Acceptable, well-documented publication meeting basic scientific principles
- Objective of study:
- metabolism
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- The lipolytic activity of human gastric and duodenal juice against medium chain and long chain triglycerides was compared.
- GLP compliance:
- no
- Species:
- human
- Route of administration:
- other: in vitro testing
- Metabolites identified:
- yes
- Details on metabolites:
- Products of Lipolysis and Positional Specificity:
The specificity of pancreatic lipase for the 1 -ester bond in LCT has been demonstrated previously by establishing the formation of 2 -monoglycerides and fatty acid as end products of lipolysis. This procedure cannot be used for MCT because medium chain 2 -monoglycerides are either cleaved by pancreatic lipase or rapidly isomerized to the 1 -isomer which is rapidly hydrolyzed or both. Indeed, chromatographic examination of the products of hydrolysis of trioctanoin-14C showed only a small fraction of monoglyceride present. - Conclusions:
- Interpretation of results (migrated information): low bioaccumulation potential based on study results
- Executive summary:
The lipolytic activity of human gastric and duodenal juice against medium chain and long chain triglycerides was compared. The work confirmed extensive literature showing that gastric juice contains lipolytic activity, that ingested triglyceride is hydrolyzed in the stomach, even after pancreatic diversion, that lipase may be demonstrated histochemically in gastric mucosa, and that gastric mucosal homogenates have lipolytic activity. Pancreatic lipase has some activity at the pH of gastric content, which is between pH6 and pH3 in normal subjects.
- Endpoint:
- basic toxicokinetics in vivo
- 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: Acceptable, well-documented publication meeting basic scientific principles.
- Objective of study:
- absorption
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Triglycerides of known structure were fed to rats, and the distribution of the fatty acids in the triglycerides of the lymph was determined.
- GLP compliance:
- no
- Radiolabelling:
- yes
- Remarks:
- C14 labelled
- Species:
- rat
- Strain:
- not specified
- Sex:
- male
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Remarks:
- with 18.5% skim milk solids, 20% sucrose, 1.8% salt mix and 27.2% fat.
- No. of animals per sex per dose / concentration:
- 3
- Details on absorption:
- The extent of absorption of palmitic acid depended on the form in which it was fed (rates between 52 an 96 %).
Absorption was greatest when palmitic acid was fed as β-palmitoyl diolein, and least when it was fed as the free acid. - Details on metabolites:
- The results obtained showed that 85 to 90% of the fatty acids occupy the same position on the lymph triglyceride molecule as they did on the dietary triglyceride molecule before the processes of digestion and absorption.
- Conclusions:
- Absorption rates were between 52 and 96 %, depending on the lipid fed.
- Executive summary:
Rats were fed glyceryl α-[palmitate-1- C14] dioleate, glyceryl β-[palmitate-1- C14] dioleate, a mixture of oleic or linoleic acid and palmitic-1-C14acid, or a mixture of triolein or trilinolein and palmitic-1- C14acid. The position of the palmitic acid on the glycerol in the triglycerides of the lymph was determined.
When the mixtures of free acids were fed, the palmitic acid was essentially randomly distributed among all three positions of the lymph triglyceride molecules. From 85 to 90% of the palmitic acid in the dietary mixed triglycerides was found in its original position on the triglyceride molecule after the processes of digestion and absorption.
When the mixtures of triglyceride and free palmitic acid were fed, 22% of the palmitic acid in the lymph triglycerides was found to be esterified with the β position. The extent of absorption of palmitic acid depended on the form in which is was fed. Absorption was greatest when palmitic acid was fed as β-palmitoyl diolein and least when it was fed as the free acid.
- Endpoint:
- basic toxicokinetics in vivo
- Type of information:
- other: review
- Adequacy of study:
- weight of evidence
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- other: Only secondary literature (review)
- Objective of study:
- absorption
- distribution
- excretion
- metabolism
- Principles of method if other than guideline:
- not applicable; review article
- GLP compliance:
- not specified
- Radiolabelling:
- no
- Details on absorption:
- The molecular weight of MCTs is smaller than the molecular size of long-chain triglycerides (LCTs) which facilitates the action of pancreatic lipase. Threfore, MCTs are hydrolysed faster and more completely than LCTs. The hydrolysis prodcuts are rapidly absorbed, mainly as free fatty acids
- Details on distribution in tissues:
- MC fatty acids are absorbed and trnsported to the liver via the portal vein in teh solubl eform of free fatty acids, bound to serum albumin.
- Metabolites identified:
- yes
- Details on metabolites:
- MC fatty acids cross the double mitochondrial membrane rapidly, and are acylated to the acyl-coA which undergo rapid ß-oxidation, with production of acetyl-CoA. Acetly-CoA can enter various anabolic (synthesis of fattay acids, cholesterol etc.) or catabolic (degradation) biochemical pathways. Oxidation in the Krebs cycle leads to the terminal metabolites, carbon dioxide and water.
- Conclusions:
- Interpretation of results (migrated information): no bioaccumulation potential based on study results
MCTs are rapidly hydrolysed an liberate free fatty acids which are rapidly absorbed and transported to the liver where they are rapidly metabolised to acetyl-CoA (fatty acids with odd number of carbons give one terminal propionyl-CoA) that ma y enter anabolic or catabolic biochemical pathways. - Executive summary:
Medium chain fatty acid triglycerides (MCT) are rapidly hydrolysed to the free fatty acids and glycerol. The fatty acids are then rapidly transported to the liver where primarily mitochondrial metabolism takes place. Acetyl-CoA produced during ß-oxidation may be utilised for biosynthesis or for energy supply. The terminal metabolites are water and carbon dioxide (Bach and Babayan 1982; see also CLH reports (Austria, 2001 and 2012) on octanoic, nonanoic, and decanoic acids [see assessment reports in section 13], Papamandiaris et al. 1998; Traul et al. 2000 [section 13].
MCT are used in patients who need parenteral infusions, or in the treatment of obese because the caloric contents of MCT is less than that of dietary fats and oils. No adverse effects were seen in MCT safety studies even at high doses, nor in treated patients. The therapeutic effect (body weight reduction) was, however, found to be questionable (Papamandiaris et al. 1998).
- Endpoint:
- basic toxicokinetics in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1970
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Acceptable, well documented publication which meets basic scientific principles
- Objective of study:
- metabolism
- Principles of method if other than guideline:
- no guideline required
- GLP compliance:
- not specified
- Radiolabelling:
- not specified
- Species:
- rat
- Strain:
- Wistar
- Sex:
- female
- Route of administration:
- other: in vitro perfused liver
- Vehicle:
- not specified
- Duration and frequency of treatment / exposure:
- single
- Remarks:
- Doses / Concentrations:
5 mM - No. of animals per sex per dose / concentration:
- 4 per group
- Control animals:
- yes, concurrent vehicle
- Metabolites identified:
- not specified
- Conclusions:
- Interpretation of results (migrated information): no data
The test substance produced biochemical alterations in the perfused rat liver. - Executive summary:
The perfusion of rat liver with a 5 mM solution of the test substance increased the amount of ß-hydroxybutyrate, acetoacetate and glucose. The formation of ketone bodies increased as well as the ratio of hydroxybutyrate to acetoacetate (Krebs, 1970).
- Endpoint:
- basic toxicokinetics in vivo
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1998
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- other: Review, secondary source
- Objective of study:
- metabolism
- Principles of method if other than guideline:
- no guideline required
- GLP compliance:
- not specified
- Radiolabelling:
- not specified
- Species:
- other: mammalian species
- Strain:
- not specified
- Sex:
- not specified
- Route of administration:
- oral: unspecified
- Vehicle:
- not specified
- Duration and frequency of treatment / exposure:
- no data
- Remarks:
- Doses / Concentrations:
no data - No. of animals per sex per dose / concentration:
- no data
- Control animals:
- not specified
- Details on absorption:
- Like other linear aliphatic carboxylic acids, nonanoic acid can be assumed to be readily absorbed from the intestine.
- Metabolites identified:
- not specified
- Conclusions:
- Interpretation of results (migrated information): no bioaccumulation potential based on study results
Nonanoic acid is readily absorbed after oral uptake, metabolised and excreted or used in intermediary metabolism. - Executive summary:
Like other linear aliphatic carboxylic acids, nonanoic acid can be assumed to be readily absorbed from the intestine.
As a common fatty acid, nonanoic acid will undergo biotransformation in
established metabolic pathways (oxidation and tricarboxylic pathway). Degradation products will either be
exhaled as CO2 or recycled within the intermediary metabolism (WHO, 1998).
Referenceopen allclose all
The proportions of neutral fat and phospholipids in the lymph were in all three cases about the same. 90% of the fatty acids were present in the neutral fat and the remaining 10 % in phospholipids. The neutral fat consisted chiefly of triglycerides; cholesterol and cholesterol esters representing only a minor part of this fraction. No free fatty acids or soaps appeared in the lymph.
The results indicated that glycerides might be completely hydrolysed in the intestinal lumen of the rat and then resynthesized in the intestinal wall.
Enzymatic Lipolysis by Gastric and Duodenal Juice:
All samples of gastric juice showed lipolytic activity against trioctanoin and triolein. Hydrolysis of emulsified trioctanoin was greater than of emulsified triolein. Hydrolysis of unemulsified trioctanoin was less and more variable. Duodenal juice was more active, even against unemulsified trioctanoin and triolein. Duodenal juice was more active against unemulsified substrate than gastric juice against emulsified substrate.
Table 1: Hydrolysis of trioctanoin and triolein*
|
Substrate and form (μmoles) |
Hydrolysis (%) |
|
|
Trioctanoin |
Triolein |
|
Gastric juice |
30, unemulsified |
21 |
1 |
|
60, emulsified |
33 |
16 |
Duodenal juice |
30, unemulsified |
40 |
34 |
|
45, emulsified |
42 |
35 |
|
105, emulsified |
45 |
36 |
*Gastric or duodenal juice (1 mL) was incubated (1 hour, continuous shaking, 37ºC) with 1 mL of buffer and unemulsified substrate or 1 mL of substrate emulsified in 10 mM sodium taurodeoxycholate, pH6.
pH Optimum
In the presence of bile acids, gastric lipolytic activity against trioctanoin had a broad pH optimum, between 4 and 7. The lipolytic activity of duodenal juice had a sharper pH optimum, between 6 and 8. The pH optimum was lower for short chain triglycerides, indicating that pH optimum values for lipases must be defined for a particular substrate.
Chain Length Specificity
Lipolysis rates increased with decreasing chain lengths for pure triglycerides.
Tributyrin was cleaved more rapidly than trihexanoin which in turn was cleaved more rapidly than trioctanoin (ratio of rates, 100:69:53). Because the pH optimum of gastric lipase is lower for short chain triglycerides than for MCT, trihexanoin and tributyrin were cleaved much more rapidly than, for example, trioctanoin at pH5.
Esterification and Fatty Acid Acceptors by Gastric and Duodenal Lipases
Gastric and duodenal lipases did not induce esterification of the fatty acid acceptor, glyceryl 2 -monooleyl ester, by octanoic acid over the pH range of 2 to 6. However, it was esterified by oleic acid in the presence of gastric juice, duodenal juice, or pancreatic fistula juice when bile acids were added. Esterification, calculated by disappearance of titratable fatty acid, was confirmed by TLC which showed the formation of compounds having the mobilities of a monoether monoester and a monoether diester. Control incubations without enzyme showed no loss of oleic acid or appearance of new lipids by TLC. To determine the amount of disubstituted and trisubstituted glyceryl derivatives which were formed, 14C-labeled glyceryl 2 -monooleyl ether was used and the products of the reaction were examined by zonal scanning. The glyceryl 2 -monooleyl ether was not cleaved during the incubation procedure. The amounts of ester bonds formed estimated by titration an by zonal scanning were in good agreement.
Table 2: Products of hydrolysis of trioctanoin by gastric juice*
|
Radioactivity distribution** (%) |
Lipolysis (%) |
|||
|
Monoglyceride |
Diglyceride |
Fatty acid |
Triglyceride |
|
Buffer (control) |
0 |
0 |
0 |
100 |
0 |
Gastric juice 1 mL |
3 |
26 |
26 |
44 |
34 |
3 |
28 |
24 |
43 |
33 |
|
4 |
28 |
25 |
43 |
36 |
|
4 |
28 |
25 |
43 |
36 |
|
Duodenal juice |
|
|
|
|
|
0.4 mL |
4 |
9 |
15 |
72 |
26 |
0.5 mL |
4 |
14 |
20 |
62 |
40 |
*Glyceryl trioctanoate-1-14C was added to 1 mL of emulsified trioctanoin (60 μmoles) and incubated for 1 hour at 37ºC with buffer (blank) or gastric or duodenal juice. The reaction mixture was extracted and a 50 μL aliquot was analyzed by TLC and zonal scanning. A 3 mL aliquot was titrated to quantify fatty acids liberated.
Table 1:
Specific activity of lymph triglycerides as percentage of specific activity of fed lipids
Fat fed |
%* |
Oleic acid (2 moles) and 1 mole of palmitic-1-C14acid |
64, 73, 71 |
Linoleic acid (2 moles) and 1 mole of palmitic-1-C14acid |
58, 58, 63 |
Palmitate-oleate-oleate triglyceride |
85, 85, 81 |
Oleate-palmitate-oleate triglyceride. |
94, 96, 92 |
Oleic acid (2 moles) as triolein and 1 mole of palmitic-1-C14acid |
59, 54, 54 |
Linoleic acid (2 moles) as trilinolein and 1 mole of palmitic-1-C14acid |
52, 54, 53 |
*Each value is the percentage obtained in a single experiment
Liver perfusion with a 5 mM solution of the test substance increased the amount of ß-hydroxybutyrate, acetoacetate and glucose. acetoacetate. The formation of ketone bodies (sum of ß-hydroxybutyrate and acetoacetate) increased (and also the ratio of hydroxybutyrate to acetoacetate). The following table shows the corresponding mean values and standard deviations.
ß-hydroxybutyrate (µmol/h/g) |
Acetoacetate (µmol/h/g) |
Total ketone bodies formation (µmol/h/g) |
Glucose (µmol/h/g) |
|
Control |
19.6 ± 1.9 |
10.8 ± 0.9 |
30.4 ± 3.3 |
8.4 ± 1.6 |
5 mM |
47.3 ± 7.6 |
32.8 ± 4.2 |
103 ± 12 |
16.8 ± 1.8 |
Like other linear aliphatic carboxylic acids, nonanoic acid can be assumed to be readily absorbed from the intestine.
As a common fatty acid, nonanoic acid will undergo biotransformation in
established metabolic pathways (oxidation and tricarboxylic pathway). Degradation products will either be
exhaled as CO2 or recycled within the intermediary metabolism.
Description of key information
There is no toxicokinetics information available on tripelargonin.
There are studies available on similar structures, which indicate that the bioaccumulation potential is likely to be low.
Key value for chemical safety assessment
- Bioaccumulation potential:
- no bioaccumulation potential
Additional information
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.
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