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EC number: 271-676-4 | CAS number: 68603-84-9
- 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 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
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 2000
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- other: Handbook, 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:
- other: no data
- Vehicle:
- not specified
- Details on exposure:
- no data
- 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
- Metabolites identified:
- not specified
- Conclusions:
- Interpretation of results (migrated information): no bioaccumulation potential based on study results
The test substance is metabolised in the liver via ß-oxidation. There was no accumulation in tissues. - Executive summary:
Nonanoic acid is metabolized in the liver via beta-oxidation, producing ketone bodies. No chain elongation or tissue storage of the acid was observed in rats. Metabolism of the terminal propionic acid residue resulted in increased glucose and glycogen synthesis (Cragg, 2001).
- 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).
- Endpoint:
- basic toxicokinetics
- Type of information:
- other: review
- Adequacy of study:
- weight of evidence
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- other: Secondary literature (review, tables, book)
- GLP compliance:
- no
- Radiolabelling:
- no
- Species:
- other: several (review article)
- Conclusions:
- Interpretation of results (migrated information): no bioaccumulation potential based on study results
Pelargonic acid is an odd-numbered naturally occurring fatty acid. Abbsorption, distribution, metabolism and excretion is very similar across all fatty acids. ß-oxidation is the main metabolic pathway where odd-numbered fatty acids like pelargonic acid finally lead to propionyl-CoA. This is further metabolised to CO2 and water in the intermediary metabolism, similar to acetyl-CoA which results from the even-numbered fatty acids. - Executive summary:
Like all other naturally occurring fatty acids, pelargonic acid is utilized as food substrate for virtually all life forms including bacteria, fungi, algae, plants, animals and human beings. Fatty acids are required for teh organism's energy supply and biosynthesis of a variety of biomolecules including adipose and membrane lipids.
Absorption takes place through the cell membranes of the intestinal brush border cells of the jejunum, regardless of whether the fatty acid moiety is ingested as free fatty acid, as a salt or as a component of lipids. Short and intermediate chain fatty acids, like pelargonic acid, are absorbed directly and rapidly from the intestinal lumen into the portal circulation where they are bound to serum proteins and are transported to the liver and other tissues.
ß-oxidation in the mitochondria is the main metabolic pathway. Even-numbered fatty acids are degraded via ß-oxidation to CO2 and acetyl-CoA, under the release of biochemical energy. Odd-numbered fatty acids like pelargonic acid are similarly decomposed to CO2 and propionyl-CoA. The latter undergoes further degradation to succinyl-CoA resp. acetyl-CoA. These compounds are oxidized via the citric acid cycle to CO2 and water. No other ultimate excretion products than CO2 and water will be formed (GAB Consulting, 2003)
Referenceopen allclose all
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.
1. Introduction
Fatty acids are aliphatic, saturated carbon acids with non-branched carbon chains. Pelargonic Acid is a fatty acid with nine carbons:
CH3(CH2)7COOH.
As all fatty acids, Pelargonic Acid is present in nature and has been found in various plants as well as in a variety of animal fats and foods of animal origin. The absorption, distribution, metabolism and excretion characteristics are well known and described in medical and biochemical text books. A brief summary is given below. .
2. Absorption
Non-esterified short-chain fatty acids, like Pelargonic Acid, are rapidly absorbed from the lumen of the intestine directly into the portal blood stream. This entry is sodium-dependent and can take place against concentration gradient by a process of active transport (Bell et al. 1976).
Fats, however, are not able to pass as such the intestine brushborder cells. They must be emulsified by bile salts and then undergo lipolysis under the influence of pancreatic lipase (Bell et al. 1976). By the breakage of the triglyceride at the two primary positions, fatty acids and monoglycerides will be formed. They are able to form water soluble micelles, with the polar, hydrophilic hydroxyl- and carboxyl-groups facing outwards and the hydrophobic moieties directed inwards. In this form, the micelles passively transported into cells with the aid of bile acis, either by dissolving in the membrane or by pinocytosis.
Most fats are between 95 and 100% digestable. Longer-chain fatty acids are less well absorbed than shorter-chain fatty acids (Guthrie and Andrews 1975). In the case of Pelargonic Acid complete and rapid absorption can be expected. A profound description of the involved enzymatic processes is given by Orten and Neuhaus (1975).
3. Distribution
About 70% of the absorbed micelles are resynthesized immediately to form triglycerides (Guthrie and Andrews 1975), starting with the fatty acid activation to fatty acyl-CoA derivatives. These react with L-alpha-glycerophosphate to yield glyceride phosphates which then are hydrolyzed to form the corresponding glycerides. The enzymatic steps are described in detail by Orten and Neuhaus (1975).
Further transportation follows in at least three forms, as
- chylomicrons (aggregates of triglycerides (80%), phospholipids (7%) and cholesterol (9%) which are “coated” with lipoproteins)
- lipids associated with proteins as lipoproteins
- non-esterified fatty acids (NEFA) loosely bound to albumin.
Chilomicrons and lipoproteins are predominantly are transported from the intracellular fluid into the lacteal and the lymphatics, and finally into the systemic blood stream (Orten and Neuhaus 1975).
Non-esterified fatty acids (NEFAs) are mainly transported through the portal blood system loosely bound to plasma albumin (Orten and Neuhaus 1975). While the amount of NEFAs in the plasma is very small (0.1-0.3 g/L in fasting adults), they apparently represent the mobile form for oxidation to meet energy needs. They have an exceedingly high turnover rate, with a half-life of only 2 to 3 minutes (Orten and Neuhaus 1975).
A large proportion of absorbed fat is carried to the liver, the chief site for its metabolic disposal. Triglycerides entering the liver as chilomicrons are hydrolyzed to their constituent fatty acids and glycerol. Both compounds may be utilized to form phospholipids and lipoproteins. The lipoproteins, which can contain 55 to 90% fat, facilitate the transport of fat throughout the body where it is used as a source of energy or may be stored in the fat depots of each cell, or in special adipose cells, for future use (Guthrie and Andrews 1975). Fat is either oxidized - mainly in the liver and muscles - or is stored – mainly in the subcutaneous or retroperitoneal adipose tissues (Bell et al. 1972).
4. Metabolism
Fatty acids are utilized as a carbon source (biosynthesis of long-chain fatty acids, phospholipids and other lipids, amino acids, steroids etc.) and as a source of energy (oxidation to CO2and acetyl CoA and further to CO2and water). Biosynthesis and degradation occur by separate pathways and in different compartments. Biosynthesis is located in the cytoplasma and β-oxidation in mitochondria. Thus, both processes can occur simultaneously according to needs.
Acetyl-CoA from fatty acids (or from pyruvate) may be regarded as the main central metabolite of many various substance classes. A multienzyme complex (fatty acid synthetase) catalyzes long-chain saturated fatty acids from acetyl-CoA, malonyl-CoA and reduced nicotinamide-adenine-dinucleotide phosphate (NADPH) according to the following stoichometric biosynthesis, e.g. for palmitate:
CH3CO – SCoA + 7HOOCCH2CO – SCoA + 14NADPH + 14H+→ CH3(CH2)14CO2H + 7CO2+ 14NADP++ 8CoA + 6H2O.
The stepwise following synthesis is described in detail (Orten and Neuhaus 1975, and by Thabrew and Ayling 2001). The authors give also details on the formation of other substance classes.
The oxidative degradation of fatty acids is a universal biochemical capability among living organisms. Fatty acids are the form in which fat is liberated from the depots. Albumin carries the fatty acids in the bloodstream to other tissues, like liver, heart, and kidneys (Zubay 1983). Intracellularly, fatty acid oxidation occurs principally in the mitochondria; ß-oxidation is the normal mechanism, in which two-carbon units are sequentially removed beginning from the carboxyl-terminal end (Orten and Neuhaus 1975). The pathway for the oxidation of fatty acids is illuistrated in Figure 1 of the attached document. The parent even-numbered fatty acid is activated by conversion to the fatty acyl-CoA, oxidized to the alpha, beta-unsaturated compound, hydrated, oxidized to the beta-keto derivative, and finally subjected to a thiolytic cleavage yielding acetyl-CoA and the fatty acyl-CoA containing two less carbon atoms, which, in turn, undergoes the same series of reactions (Mahler and Cordes 1971). Each of these steps is exhaustively described by the a.m. authors and by Bell et al. 1972. A detailed chapter on the enzymology of beta-oxidation is written by Zubay 1983.
Oxidation of fatty acids with an odd number of carbons: The sequence of reactions as summarized above for the oxidation of even-numbered fatty acids is also applicable to the oxidation of those with an odd number of carbon atoms. Consequently, straight-chain fatty acids with e.g. 9 carbons are oxidized by the normal ß-oxidation sequence and give rise to 3 acetyl-CoAs and 1 propionyl-CoA:
CH3CH2C-CoA
The propionyl-CoA is converted to succinyl-CoA (as indicated in Fig. 2 of the attached document) which can be further metabolized in the tricarboxylic acid cycle, finally to yield CO2and water. Two other pathways for the utilization of propionyl-CoA finally to form acetyl-CoA have been described by Mahler and Cordes 1971 and are also depicted in Fig 2.
5. Excretion
As a result of β-oxidation, which represents the by far major pathway for the metabolism of fatty acids, long-chain fatty acids are stepwise degraded to short-chain fatty acids and these to succinyl CoA resp. acetyl-CoA plus CO2. These compounds are further oxidated via the citric acid cycle to CO2 and water. No other ultimate excretion products than CO2and water will be formed.
6. References: cf. attached document
Description of key information
Fatty acids, main constituents of this UVCB substance, are typically unbranched, with different chain length. They are found in all living organism fulfilling three fundamental roles. Besides their function as part of molecules like phospholipids and glycolipids important for the cell-structure, they are often precursors of signalling molecules such as prostanoids in animals or phytohormones in plants. The third and best understood role of fatty acid is their role as an energy source, particularly in higher animals and plants. According the available data in the literature, fatty acids are almost completely absorbed after oral intake, whereas only limited dermal uptake has to be expected. The major metabolic pathway for linear fatty acids is the β-oxidation pathway for energy generation, while alternatives are the α- and ω-oxidation. Besides this, fatty acids are stored as lipids in adipose tissue, used as part of cellular membranes, as well as precursors for signalling molecules and even long chain fatty acids. It can be summarized:
Rapid absorption of free fatty acids from the gut following ingestion of either natural or synthetic (MCT) fats and oils or of free fatty acid or its salt.
Rapid and complete metabolism in the liver, with no other metabolites than carbon dioxide and water.
No bioaccumulation.
Key value for chemical safety assessment
- Bioaccumulation potential:
- no bioaccumulation potential
- Absorption rate - oral (%):
- 100
Additional information
Pelargonic acid, the main constituent of the target substance, is a naturally occurring fatty acid (see also the assessment of the Marin Municipal Water District in section 13), and pelargonic acid esters are used as a food flavoring substance (cf. WHO Technical Report No. 868 in section 13). Like all other naturally occurring fatty acids, pelargonic acid is utilized as food substrate for virtually all life forms including bacteria, fungi, algae, plants, animals and human beings (Zschintzsch, 2003). Fatty acids are required for the organism's energy supply and biosynthesis of a variety of biomolecules including adipose and membrane lipids.
In mammals and humans, absorption takes place through the cell membranes of the intestinal brush border cells of the jejunum, regardless of whether the fatty acid moiety is ingested as free fatty acid, as a salt or as a component of lipids. Short and intermediate chain fatty acids, like pelargonic acid, are absorbed directly and rapidly from the intestinal lumen into the portal circulation where they are bound to serum proteins and are transported to the liver and other tissues (Zschintzsch, 2003).
ß-oxidation in the mitochondria is the main metabolic pathway (Zschintzsch, 2003; Cragg, 2001; WHO, 1998). Even-numbered fatty acids are degraded via ß-oxidation to CO2and acetyl-CoA, under the release of biochemical energy. Odd-numbered fatty acids like pelargonic acid are similarly decomposed to CO2and propionyl-CoA. The latter undergoes further degradation to succinyl-CoA resp. acetyl-CoA. These compounds are oxidized via the citric acid cycle to CO2and water. No other ultimate excretion products than CO2and water will be formed. Thus, pelargonic acid or metabolites thereof are unlikely to accumulate (Zschintzsch, 2003).
Medium Chain fatty acid Triglycerides (MCT) represent another source of fatty acids. The fatty acid composition may vary from one MCT to the other MCT preparation. 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).
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