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EC number: 500-204-4 | CAS number: 68334-05-4
- 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

Endpoint summary
Administrative data
Link to relevant study record(s)
Description of key information
Key value for chemical safety assessment
Additional information
Basic toxicokinetics
There are no studies available in which the toxicokinetic behaviour of Fatty acids, C18-unsaturated dimers, 2-ethylhexyl esters (CAS 68334-05-4) has been investigated.
Therefore, in accordance with Annex VIII, Column 1, Item 8.8.1, of Regulation (EC) No 1907/2006 and with Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance (ECHA, 2012c), assessment of the toxicokinetic behaviour of the substance Fatty acids, C18 -unsaturated dimers, 2-ethylhexyl esters is conducted to the extent that can be derived from the relevant available information. This comprises a qualitative assessment of the available substance specific data on physico-chemical and toxicological properties according to Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance (ECHA, 2012c) and taking into account further available information on structurally similar substances and hydrolysis products.
The substance Fatty acids, C18 -unsaturated dimers, 2-ethylhexyl esters is a liquid at room temperature and has a molecular weight of 673.10 g/mol, and a water solubility < 1 mg/L at 21 °C. The log Pow and the vapour pressure is estimated to be >10 and < 0.0001 Pa at 20 °C (calculated).
Absorption
Absorption is a function of the potential for a substance to diffuse across biological membranes. The most useful parameters providing information on this potential are the molecular weight, the octanol/water partition coefficient (log Pow) value and the water solubility. The log Pow value provides information on the relative solubility of the substance in water and lipids (ECHA, 2012c).
Oral:
The smaller the molecule, the more easily it will be taken up. In general, molecular weights below 500 are favourable for oral absorption (ECHA, 2012c). As the molecular weight of Fatty acids, C18 -unsaturated dimers, 2-ethylhexyl esters is 673.10 g/mol, absorption of the molecule in the gastrointestinal tract is considered to be low.
If absorption occurs, the favourable mechanism will be absorption by micellar solubilisation, as this mechanism is of importance for highly lipophilic substances (log Pow > 4), which are poorly soluble in water (1 mg/L or less) like Fatty acids, C18 -unsaturated dimers, 2-ethylhexyl esters with a log Pow > 10 and a water solubility < 1 mg/L.
No studies by the oral route are available for Fatty acids, C18 -unsaturated dimers, 2-ethylhexyl esters, thus no additional information from animal studies is available.
After oral ingestion, an ester undergoes stepwise hydrolysis of the ester bond by gastrointestinal enzymes (Lehninger, 1970; Mattson and Volpenhein, 1972). The respective alcohol as well as the corresponding acid is formed. In general, the physico-chemical characteristics of the cleavage products (e.g. physical form, water solubility, molecular weight, log Pow, vapour pressure, etc.) are likely to be different from those of the parent substance before absorption into the blood takes place, and hence the predictions based upon the physico-chemical characteristics of the parent substance do no longer apply (ECHA, 2012c). For the expected cleavage product 2-ethylhexanol, it is known that it will be absorbed in the gastro-intestinal tract by dissolution into the gastrointestinal fluids quite rapidly (Deisinger, 1994). The second cleavage product, Fatty acids, C18 unsatd., dimers, seems to be less absorbed than monomeric fatty acids, as indicated by studies carried out to investigate the absorption, distribution and excretion of dimeric fatty acids (Hsieh and Perkins, 1975). Upon oral administration only ca. 0.4% of the 14C-labeled dimeric fatty acid methyl esters given by gastric intubation were absorbed within 12 h. Ca. 1% of the labeled material was excreted via urine and ca. 2% as CO2. Ca. 80% of the radioactivity was recovered in the gastrointestinal tract and the faeces. About 0.115% of the administered test material was incorporated in the liver and metabolized to different lipid classes.
Overall, a systemic bioavailability of Fatty acids, C18 -unsaturated dimers, 2-ethylhexyl esters and/or the respective cleavage products in humans is considered possible but limited after oral uptake of the substance due to its high molecular weight.
Dermal:
The smaller the molecule, the more easily it may be taken up. In general, a molecular weight below 100 favours dermal absorption, above 500 the molecule may be too large (ECHA, 2012c). As the molecular weight of Fatty acids, C18 -unsaturated dimers, 2-ethylhexyl esters is 673.10 g/mol, dermal absorption of the molecule is not likely.
If the substance is a skin irritant or corrosive, damage to the skin surface may enhance penetration (ECHA, 2012). As Fatty acids, C18 -unsaturated dimers, 2-ethylhexyl esters is not skin irritating in humans, enhanced penetration of the substance due to local skin damage can be excluded.
For substances with a log Pow above 4, the rate of dermal penetration is limited by the rate of transfer between the stratum corneum and the epidermis, but uptake into the stratum corneum will be high. For substances with a log Pow above 6, the rate of transfer between the stratum corneum and the epidermis will be slow and will limit absorption across the skin, and the uptake into the stratum corneum itself is also slow. The substance must be sufficiently soluble in water to partition from the stratum corneum into the epidermis (ECHA, 2012). With a log Pow > 10 and a water solubility < 1 mg/L, dermal uptake of Fatty acids, C18 -unsaturated dimers, 2-ethylhexyl esters is likely to be low.
In support of this, data available for several fatty acids indicate that the skin penetration both in vivo (rat) and in vitro (rats and human) decreases with increasing chain length. Thus, after 24 h exposure about 0.14% and 0.04% of C16 and C18 soap solutions are absorbed through human epidermis applied in vitro at 217.95 µg C16/cm² and 230.77 µg C18/cm². At 22.27 µg C16/cm² and 24.53 µg C18/cm², about 0.3% of both C16 and C18 soap solutions is absorbed through rat skin after 6 h exposure in vivo (Howes, 1975).
Inhalation:
Fatty acids, C18 -unsaturated dimers, 2-ethylhexyl esters has a low vapour pressure below 0.0001 Pa thus being of low volatility. Therefore, under normal use and handling conditions, inhalation exposure and thus availability for respiratory absorption of the substance in the form of vapours, gases, or mists is considered negligible.
However, the substance may be available for respiratory absorption in the lung after inhalation of aerosols, if the substance is sprayed. In humans, particles with aerodynamic diameters below 100 μm have the potential to be inhaled. Particles with aerodynamic diameters below 50 μm may reach the thoracic region and those below 15 μm the alveolar region of the respiratory tract (ECHA, 2012c). Lipophilic compounds with a log Pow > 4, that are poorly soluble in water (1 mg/L or less) like Fatty acids, C18 -unsaturated dimers, 2-ethylhexyl esters can be taken up by micellar solubilisation.
In an acute aerosol inhalation study with Fatty acids, C18 -unsaturated dimers, 2-ethylhexyl esters performed according to OECD guideline 436 (acute toxic class method, limit test), an LC50 value of greater than 5.3 mg/L was found for rats. No effects were observed indicating absorption after inhalation.
Overall, a systemic bioavailability of Fatty acids, C18 -unsaturated dimers, 2-ethylhexyl esters in humans is considered to be low.
Accumulation
Highly lipophilic substances tend in general to concentrate in adipose tissue, and depending on the conditions of exposure may accumulate. Although there is no direct correlation between the lipophilicity of a substance and its biological half-life, it is generally the case that substances with high log Pow values have long biological half-lives. The high log Pow of > 10 implies that with Fatty acids, C18 -unsaturated dimers, 2-ethylhexyl esters may have the potential to accumulate in adipose tissue (ECHA, 2012c).
Absorption is a prerequisite for accumulation within the body. Due to its MW and high log Pow, absorption is expected to be minimal for with Fatty acids, C18 -unsaturated dimers, 2-ethylhexyl esters, therefore accumulation is not favoured as well. In case of esterase-catalysed hydrolysis, the cleavage products with Fatty acids, C18-unsaturated dimers and 2–ethylhexanol are produced. 2-ethylhexanol is known to be metabolized and excreted well, thus no accumulation is expected (Deisinger, 1994). The second cleavage product, the fatty acid, can be stored as triglycerides in adipose tissue depots or be incorporated into cell membranes. At the same time, fatty acids are also required as a source of energy. Thus, stored fatty acids underlie a continuous turnover as they are permanently metabolized and excreted. Bioaccumulation of fatty acids only takes place, if their intake exceeds the caloric requirements of the organism. The available information indicates that dimeric fatty acids are poorly absorbed and that the absorbed fraction follows the same pattern of metabolism and excretion as the monomeric acids. Thus, no significant bioaccumulation in adipose tissue is expected.
Overall, the available information indicates that no significant bioaccumulation of the parent substance in adipose tissue is anticipated.
Distribution
Distribution within the body through the circulatory system depends on the molecular weight, the lipophilic character and water solubility of a substance. In general, the smaller the molecule, the wider is the distribution. If the molecule is lipophilic, it is likely to distribute into cells and the intracellular concentration may be higher than extracellular concentration particularly in fatty tissues (ECHA, 2012c).
Distribution of the parent substance is not expected as only very limited absorption will occur. Only the potential cleavage products of Fatty acids, C18 -unsaturated dimers, 2 -ethylhexyl esters might be distributed within the body.
Metabolism
Esters of fatty acids are hydrolysed to the corresponding alcohol and fatty acid by esterases (Fukami and Yokoi, 2012). Depending on the route of exposure, esterase-catalysed hydrolysis takes place at different places in the organism: After oral ingestion, esters of alcohols and fatty acids undergo enzymatic hydrolysis already in the gastro-intestinal fluids. In contrast, substances that are absorbed through the pulmonary alveolar membrane or through the skin enter the systemic circulation directly before entering the liver where hydrolysis will basically take place. Dimeric acids are of more complex structure than the simple fatty acid esters, therefore, ester bond hydrolysis is expected to occur to a minor extent. Nevertheless possible cleavage products should be discussed here. The first possible cleavage product, 2-ethylhexanol, is metabolized by oxidation and/or glucuronidation. The metabolism of 2 -ethylhexanol (CAS 104 -76 -7) was studied in rats (Deisinger, 1994). Upon oral application, 2 -ethylhexanol was absorbed effectively by the gastrointestinal tract. The major portion of the dose was excreted within 24 h, primarily in the urine. Smaller amounts of the dose were excreted in the faeces primarily within 24 h. A mean of 11% of the dose was recovered as 14CO2, but only a fraction of a percent of the dose was recovered from the breath as [14C] volatile organics. Upon dermal application, only a small portion of the dose was absorbed, which was eliminated primarily in the urine, with smaller amounts eliminated in the faeces, and as 14CO2, in the breath.
The second cleavage product, the fatty acid, is stepwise degraded by beta-oxidation based on enzymatic removal of C2 units in the matrix of the mitochondria in most vertebrate tissues. The C2 units are cleaved as acyl-CoA, the entry molecule for the citric acid cycle. The omega- and alpha-oxidation, alternative pathways for oxidation, can be found in the liver and the brain, respectively (CIR, 1987). The cyclic portion of dimers cannot be degraded by β- or ω-oxidation and is probably hydroxylated or conjugated, which are common detoxification mechanisms of cyclic compounds, leading to polar metabolites readily excreted via urine (Iwaoka and Perkins, 1976). Likewise, after oxidative degradation of aromatic fatty acids, the remaining structure can be excreted in the urine after conjugation with glycine or glutamine in a similar way as in the case of benzoic and phenylacetic acid, respectively (WHO, 2000; Caldwell et al., 1980).
Overall, the part of Fatty acids, C18 -unsaturated dimers, 2 -ethylhexyl esters that has become systemically available, may be hydrolysed and the cleavage products are metabolized by beta oxidation and/or glucuronidation. However, due to its high molecular weight, absorption of the parent substance is not likely and thus, no extensive metabolism is expected but rather direct elimination.
Excretion
The main route of excretion of Fatty acids, C18 -unsaturated dimers, 2 -ethylhexyl esters is expected to be excretion of unabsorbed substance with the faeces. The second route of excretion is expected to be by expired air as CO2 after metabolic degradation (beta-oxidation). The potential cleavage products might also be excreted via the urine, unchanged or metabolised and exhaled (Deisinger, 1994; Hsieh and Perkins, 1976).
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