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EC number: 211-016-4 | CAS number: 627-89-4
- 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
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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 were no studies available in which the toxicokinetic behaviour of isopentyl oleate (CAS 627-89-4) 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, 2014c), assessment of the toxicokinetic behaviour of the substance isopentyl oleate (CAS 627-89-4) 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, 2014c) and taking into account further available information on structurally analogue substances and hydrolysis products.
The substance isopentyl oleate (CAS 627-89-4) is an organic liquid with a molecular weight of 326.56 - 354.61 g/mol. The measured water solubility and predicted log Pow were <3.0 µg/L at 20 °C and 5.27, respectively.
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, 2014c).
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, 2014c). As the molecular weight of isopentyl oleate is 326.56 - 354.61 g/mol, absorption of the molecule in the gastrointestinal tract is considered to be possible. 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 isopentyl oleate with a log Pow of 5.27 and a water solubility of <3 µg/L.
In two acute oral toxicity studies with the structurally analogue substances isopropyl oleate (CAS 112-11-8) and Fatty acids, C16-18 and C18-unsatd., Bu esters (CAS 84988-79-4) performed according to OECD TG 401 and 423 (limit test) LD50 values of >2000 mg/kg bw were derived.
After oral ingestion, all fatty acid esters of the analogue approach undergo stepwise hydrolysis of the ester bonds by gastrointestinal enzymes to the corresponding alcohol and fatty acid by esterases (Fukami and Yokoi, 2012; Lehninger, 1970; Mattson and Volpenhein, 1972). The esterases catalysing the reaction are present in most tissues and organs, with particularly high concentrations in the GI tract and the liver (Fukami and Yokoi, 2012). The respective alcohol as well as the fatty acid is formed. For isopentyl oleate (CAS 627-89-4) the expected breakdown products of ester hydrolysis are isopentanol and oleic acid with a carbon chain length of C18. 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, and hence the predictions based upon the physico-chemical characteristics of the parent substance do no longer apply (ECHA, 2012). However, also for both cleavage products, it is anticipated that they are absorbed in the gastro-intestinal tract. The highly lipophilic fatty acid (oleic acid) is absorbed by micellar solubilisation (Ramirez et al., 2001) and can be distributed within the body, whereas the water soluble alcohol (isopentanol) is readily dissolved into the gastro-intestinal fluids.
Overall, a systemic bioavailability of isopentyl oleate and/or the respective hydrolysis products in humans is considered possible.
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, 2014c). As the molecular weight of isopentyl oleate is 326.56 - 354.61 g/mol, dermal absorption of the molecule is likely.
If the substance is a skin irritant or corrosive, damage to the skin surface may enhance penetration (ECHA, 2014c). As isopentyl oleate 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, 2014c). With a log Pow of 5.27 and a water solubility <3 µg/L, dermal uptake of isopentyl oleate is likely to be low.
In an acute dermal toxicity study with the structurally analogue substance Fatty acids, C16-18 and C18 unsatd. branched and linear, butyl esters (CAS 163961-32-8) performed according to OECD TG 402, a LD50 value of >2000 mg/kg bw was derived.
In support of this, QSAR based dermal permeability prediction (DERMWIN V2.02.2012) using molecular weight, log Pow and water solubility was performed resulting in a dermal penetration rate of 1.38E-03 µg/cm²/h for isopentyl oleate (CAS 627-89-4). This value is considered as an indicator for a very low dermal absorption rate for isopentyl oleate of <1% (Mostert & Goergens, 2011).
Overall, the available dermal toxicity data with the structurally analogue substance Fatty acids, C16-18 and C18 unsatd. branched and linear, butyl esters and the calculated dermal absorption rate of isopentyl oleate do not reveal any systemic toxicity.
Inhalation
Isopentyl oleate has a predicted low vapour pressure of 0.0001 Pa (QSAR calculation, SPARC v4.6.), 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, 2014c). Lipophilic compounds with a log Pow >4, that are poorly soluble in water (1 mg/L or less) like isopentyl oleate can be taken up by micellar solubilisation.
Overall, a systemic bioavailability of isopentyl oleate 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 5.27 implies that isopentyl oleate may have the potential to accumulate in adipose tissue (ECHA, 2014c).
Absorption is a prerequisite for accumulation within the body. The high log Pow value of isopentyl oleate implies that it has the potential to accumulate in adipose tissue. However, as isopentyl oleate undergoes esterase-catalysed hydrolysis, the accumulation potential of the cleavage products has to be considered. Substances with high water solubility, like isopentanol do not have the potential to accumulate in adipose tissue due to their low log Pow and are thus widely distributed within the body and rapidly eliminated via renal excretion. In contrast, accumulation of the fatty acids in triglycerides in adipose tissue or the incorporation into cell membranes is possible. At the same time, fatty acids are also required as a source for energy generation.
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, 2014c).
Distribution of the parent substance is not expected as only very limited absorption will occur. Only the potential hydrolysis products of isopentyl oleate might be distributed within the body.
Metabolism
Fatty acid esters are expected to be rapidly hydrolysed to the corresponding alcohol and fatty acid by esterases (Fukami and Yokoi, 2012; Lehninger, 1970). Alcohol metabolism proceeds by oxidation to the corresponding aldehyde and acid mediated by alcohol and aldehyde dehydrogenase. Glucuronidation will also take place at all steps to facilitate urinary excretion (HSDB, 2011).
The second cleavage product, the fatty acid, is stepwise degraded by beta-oxidation based on enzymatic removal of C2 units in the matrix of mitochondria in most vertebrate tissues. The C2 units are cleaved as acyl-CoA, the entry molecular for the citric acid cycle. The omega- and alpha-oxidation, alternative pathways for oxidation can be found in the liver and the brain, respectively (Lehninger, 1970; Stryer, 1996). The products of beta-oxidation of odd-chain fatty acids are acetyl-CoA and malonyl-CoA, which cannot be oxidized further, are used in lipogenesis. Moreover even-chain fatty acids produce acetyl-CoA and succinyl-CoA, which is a gluconeogenesis precursor (Grego and Mingrone, 1994). Further oxidation of the C2-untis (acetyl-CoA) via the citric acid cycle leads to the formation of H2O and CO2 (Lehninger, 1970; Stryer, 1994). In addition glucuronidation of only partially hydrolysed monoesters has been observed (Elcombe, 1986).
This hypothesis is supported by experimental toxicokinetic data from the structurally analogue substance ethyl oleate (CAS 111-62-6). In this study performed equivalent or similar to OECD TG 417 and in compliance with GLP the absorption, distribution and excretion of radiolabeled ethyl oleate was assessed in rats after a single, oral dose of 1700 and 3400 mg/kg bw and compared with radiolabeled triacylglycerol containing only oleic acid as the fatty acid (Bookstaff, 2003). In summary, ethyl oleate is rapidly and extensively hydrolysed to free oleic acid, absorbed (75-88% of the dose), and delivered to tissue where it undergoes beta-oxidation. The basis for this conclusion is the rapid excretion of a significant percentage of the administered dose (30-40%) as CO2 within the first 6 h and 40-70% of the dose within 12 h. For this to happen, the free oleic acid moiety has to be available. A second route of elimination of radioactivity was via the feces. The mean percent dose recovered in the feces over the first 24 h post-dose was approximately 8 and 20% for the low and high doses of (14C-ethyl oleate, respectively. Renal elimination was minimal, with approximately 2% of the radioactivity recovered in urine over 72 h post-dose for the groups. At the 1.7 g/kg dose, the tissue distribution of ethyl oleate derived radioactivity was similar to that of triacylglycerol derived radioactivity. This supports the conclusion that ethyl oleate is rapidly hydrolysed to oleic acid, absorbed, and distributed within the body in the same way as dietary sources of oleic acid. The similar tissue distribution between ethyl oleate derived radioactivity and triacylglycerol derived radioactivity suggests that the radiolabel in tissue represents the same chemical form (i.e., the oleic acid moiety).
Overall, the part of isopentyl oleate that has become systemically available, may be hydrolysed and the hydrolysis products are metabolized by beta oxidation and/or glucuronidation.
Excretion
Based on the metabolism described above, the fatty acid esters and the breakdown products will be metabolised in the body to a high extent. The fatty acid components, will be metabolised for energy generation or stored as lipid in adipose tissue or used for further physiological properties e.g. incorporation into cell membranes (Lehninger, 1970; Stryer, 1996). Therefore, the fatty acid component is not expected to be excreted to a significant degree via the urine or faeces but excreted via exhaled air as CO2 or stored as described above. The second route of excretion is expected to be by biliary excretion with the faeces. For the alcohol, the main route is renal excretion via the urine due to the low molecular weight and the high water solubility (HSDB, 2011).
References:
A detailed reference list is provided in the technical dossier (see IUCLID, section 13) and within the CSR.
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