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EC number: 287-824-6 | CAS number: 85586-21-6
- 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
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- 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
Justification for grouping of substances and read-across
The short chain methyl esters category (SCAE Me) covers fatty acid esters of methanol. The category contains both mono-constituent substances, with fatty acid C-chain lengths ranging from C6 to C18 and UVCB substances, composed of single methyl esters in variable proportions. Fatty acid esters are generally produced by chemical reaction of an alcohol (e.g. methanol) with an organic acid (e.g. lauric acid) in the presence of an acid catalyst (Radzi et al., 2005). The esterification reaction is started by the transfer of a proton from the acid catalyst to the acid to form an alkyloxonium ion. The carboxylic acid is protonated on its carbonyl oxygen followed by a nucleophilic addition of a molecule of the alcohol to the carbonyl carbon of the acid. An intermediate product is formed. This intermediate product loses a water molecule and proton to give an ester (Liu et al., 2006; Lilja et al., 2005; Gubicza et al., 2000; Zhao, 2000). Monoesters are the final products of esterification of fatty acids with methanol.
In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met.” In particular, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across).
Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006, whereby substances may be considered as a category provided that their physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity, the substances listed below are allocated to the category of SCAE Me.
Table: The SCAE Me category members include:
CAS |
EC name |
MW |
Fatty acid chain length |
Type of alcohol |
Molecular formula |
106-70-7 (a) |
Methyl hexanoate |
130.18 |
C6 |
Methanol |
C7H14O2 |
111-11-5 |
Methyl octanoate |
158.24 |
C8 |
Methanol |
C9H18O2 |
110-42-9 |
Methyl decanoate |
186.29 |
C10 |
Methanol |
C11H22O2 |
111-82-0 |
Methyl laurate |
214.35 |
C12 |
Methanol |
C13H26O2 |
124-10-7 (b) |
Methyl myristate |
242.41 |
C14 |
Methanol |
C15H30O2 |
112-39-0 |
Methyl palmitate |
270.46 |
C16 |
Methanol |
C17H34O2 |
112-62-9 |
Methyl oleate |
296.49 |
C18:1 (cis) |
Methanol |
C19H36O2 |
112-63-0 |
Methyl linoleate |
294.48 |
C18:2 (cis) |
Methanol |
C19H34O2 |
112-61-8 |
Methyl stearate |
298.51 |
C18 |
Methanol |
C19H38O2 |
68937-83-7 |
Fatty acids, C6-10, methyl esters |
130.18-186.29 |
C6-10 |
Methanol |
C7H14O2; C11H22O2 |
67762-39-4 |
Fatty acids, C6-12, methyl esters |
130.18-214.35 |
C6-12 |
Methanol |
C7H14O2; C13H26O2 |
85566-26-3 |
Fatty acids, C8-10, methyl esters |
158.24-186.29 |
C8-10 |
Methanol |
C9H18O2; C11H22O2 |
67762-40-7 |
Fatty acids, C10-16, methyl esters |
186.29-270.46 |
C10-16 |
Methanol |
C11H22O2; C17H34O2 |
61788-59-8 |
Fatty acids, coco, methyl esters |
214.35-242.40 |
C12-14 |
Methanol |
C13H26O2; C15H30O2 |
308065-15-8 |
Fatty acids, C12-14 (even numbered), methyl esters |
214.35-242.40 |
C12-14 |
Methanol |
C13H26O2: C15H30O2 |
1234694-02-0 |
Fatty acids, C12-16 (even numbered) and C18-unsatd., methyl esters |
270.46-296.49 |
C16-18; C18uns. |
Methanol |
C17H34O2; C19H38O2; C19H36O2 |
68937-84-8 |
Fatty acids, C12-18, methyl esters |
214.35-296.49 |
C12-18 |
Methanol |
C13H26O2; C19H38O2 |
67762-26-9 |
Fatty acids, C14-18 and C16-18-unsatd., methyl esters |
242.40-298.51 |
C14-18; C16-18uns. |
Methanol |
C15H30O2; C19H38O2; C17H32O2; C19H36O2 |
61788-61-2 |
Fatty acids, tallow, methyl esters |
270.46-298.51 |
C16-18; C18:1 |
Methanol |
C17H34O2; C19H38O2; C19H36O2 |
67762-38-3 |
Fatty acids, C16-18 and C18-unsatd., methyl esters |
270.46-298.51 |
C16-18; C18uns. |
Methanol |
C17H34O2; C19H38O2; C19H36O2 |
85586-21-6 |
Fatty acids, C16-18, methyl esters |
270.46–298.51 |
C16-18 |
Methanol |
C17H34O2; C19H38O2 |
111-62-6 (c) |
Ethyl oleate |
310.52 |
C18:1 (cis) |
Ethanol |
C20H38O2 |
544-35-4 (c) |
Ethyl linoleate |
308.51 |
C18:2 (cis) |
Ethanol |
C20H36O2 |
68171-33-5 (c) |
Isopropyl isostearate |
326.56 |
C18iso |
Iso-propanol |
C21H42O2 |
123-95-5 (c) |
Butyl stearate |
340.60 |
C18 |
Butanol |
C22H44O2 |
22047-49-0 (c) |
2-ethylhexyl stearate |
396.70 |
C18 |
2-ethyl-hexanol |
C26H52O2 |
91031-48-0 (c) |
Fatty acids, C16-18, 2-ethylhexyl esters |
368.65-396.70 |
C16-18 |
2-ethyl-hexanol |
C24H48O2; C26H52O2 |
57-10-3 (c) |
Palmitic acid |
256.43 |
C16 |
-- |
C16H32O2 |
(a) Category members subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in bold font. Only for these substances a full set of experimental results and/or read-across is given.
(b) Substances that are either already registered under REACh or not subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in normal font. Lack of data for a given endpoint is indicated by “--“.
(c) Surrogate substances are either chemicals forming part of a related category of structurally similar fatty acid esters or precursors/breakdown products of category members (i.e. alcohol and fatty acid moieties). Available data on these substances are used for assessment of (eco )toxicological properties by read-across on the same basis of structural similarity and/or mechanistic reasoning as described below for the present category.
Grouping of substances into this category is based on:
(1) common functional groups:
All category members are esters with the ester group being the common functional group of all substances. The substances are monoesters of aliphatic alcohols (methanol) and fatty acids with the chain length C6 to C18 and C18 unsaturated. The fatty acid chains comprise carbon chain lengths ranging from C6 (e.g. methyl hexanoate, CAS 106-70-7) to C18 (e.g. methyl stearate, CAS 112-61-8), mainly saturated but also mono and di unsaturated C18 (e.g. methyl oleate, CAS 112-62-9 and methyl linoleate, CAS 112‑63‑0).
(2) common precursors and the likelihood of common breakdown products via biological processes, which result in structurally similar chemicals:
All members of the category result from esterification of the alcohol with the respective fatty acid(s). Esterification is, in principle, a reversible reaction (hydrolysis). Thus, the alcohol and fatty acid moieties are simultaneously precursors and breakdown products of the category members. For the purpose of grouping of substances, enzymatic hydrolysis in the gastrointestinal tract and/or liver is identified as the biological process, by which the breakdown of the category members result in structurally similar chemicals. Following hydrolysis, fatty acids are enzymatically degraded primarily via beta-oxidation. Alternative oxidation pathways (alpha- and omega-oxidation) are available and are relevant for degradation of branched fatty acids. Unsaturated fatty acids require additional isomerization prior to enter the beta-oxidation cycle. The methanol is slowly oxidized in the liver by the enzyme alcohol dehydrogenase (ADH) to formaldehyde, which itself is oxidized very rapidly by the enzyme aldehyde dehydrogenase (ALDH) to formic acid. Finally, formic acid is slowly metabolised to CO2 and H2O (ICPS, 2002).
(3) constant pattern in the changing of the potency of the properties across the category:
a) Physicochemical properties:
The molecular weight of the category members ranges from 130.19 to 298.5 g/mol. The physical appearance is related to the chain length of the fatty acid moiety and the degree of saturation. Thus, methyl esters up to a fatty acid chain length of C12 are liquid, the C14 methyl ester (methyl myristate, CAS 124-10-7) is a semi solid substance, methyl esters with fatty acid chain lengths of C16 and C18 are solids (methyl palmitate and methyl stearate, CAS 112-39-0 and 112-61-8). Methyl esters with unsaturated fatty acids (C18:1, C18:2) are liquid (methyl oleate and methyl linoleate, CAS 112-62-9 and 112-63-0). For all category members the vapour pressure decreases with the chain length from 496 Pa (C6 methyl ester) to circa 0.002 Pa (C18 methyl ester), for C18 unsaturated esters it is even lower. The octanol/water partition coefficient increases with increasing fatty acid chain length, ranging from log Pow = 2.34 (C6) to log Pow = 8.35 (C18), for C18 unsaturated log Pow = 7.45 (C18:1) and 6.82 (C18:2) respectively. This trend can be observed also of the water solubility where 1330 mg/L for C6 methyl ester to 0.003 mg/L for C18 methyl ester is measured. The solubility of C18 unsaturated esters are slightly higher than for saturated components. It is observed that interactions between molecules of different single substances in water result in a decrease of water solubility comparing with water solubilities of mono-constituents, e.g. for C8-C10 it is 0.3 mg/L, while for C8 (64.4 mg/L) and for C10 (10.62 mg/L) can be found. Also for C10-C16 the value (<0.06 mg/L) is much closer to the lower value for C16 (0.004 mg/L) than to the C10 value of 10.62 mg/L, or C12 value of ca. 7.8 mg/L. It is generally concluded and experimentally confirmed that all UVCBs in the category are characterized with low water solubility (<1 mg/L).
b) Environmental fate and ecotoxicological properties:
The members of the SCAE Me category are readily biodegradable and show low bioaccumulation potential in biota. Hydrolysis is not a relevant degradation pathway for these substances, due to their ready biodegradability and estimated half-lives in water > 1 year at pH 7 and 8 (HYDROWIN v2.00). The majority of the SCAE Me category members have log Koc values > 3, indicating potential for adsorption to solid organic particles. Therefore, the main compartments for environmental distribution of these substances are expected to be soil and sediment, with the exception of methyl hexanoate (CAS 106-70-7) and methyl octanoate (CAS 111-11-5), for which log Koc < 3 are reported. Therefore, these two substances will be most likely available in the water phase. Nevertheless, all substances are readily biodegradable, indicating that persistency in the environment is not expected. The vapour pressure values of methyl hexanoate and methyl octanoate (> 10 Pa) indicate potential for volatilization of these substances into air. But if released into the atmosphere both these substances are susceptible to indirect photodegradation, with half-lives of 81.6 h and 51 h, respectively (AOPWIN v1.92). This degradation pathway is not relevant for all other category members, since their vapour pressure values are low (0.0001 Pa-4.93 Pa) and no significant release into the atmosphere is expected. Regarding the aquatic toxicity profile in the category, the LC50 values reported show that fish species are the least sensitive aquatic organisms when exposed to the SCAE Me category members. On the other hand, aquatic invertebrates and algae showed the highest sensitivity to these substances. A trend in the toxicity of the monoconstituent substances of the SCAE Me category to aquatic invertebrates and algae is observed, related to the toxicity mode of action (narcosis). The toxicity increases at increasing fatty acid C-chain length (starting from C6 (CAS 106-70-7)) up to a toxicity peak at C12 (for which L(E)C50s and NOECs < 1 mg/L have been reported). With decreasing water solubility at longer C-chain lengths (C14), no toxicity up to the highest attainable concentration is observed in Daphnia and algae. Based on the available data, no toxicity to aquatic microorganisms and terrestrial organisms is to be expected for the substances of the SCAE Me category.
c) Toxicological properties:
The toxicological properties indicate that all the category members show similar toxicokinetic behaviour. The ester bond will be hydrolysed in the gastrointestinal tract before absorption and the breakdown products will be metabolised. Based on the available and reliable data, none of the category members caused acute oral, dermal or inhalation toxicity, or skin or eye irritation, or skin sensitisation. No treatment-related effects were noted up to and including the limit dose of 1000 mg/kg bw/day after repeated oral exposure, indicating that the category members have a very limited potential for toxicity. The substances did not show a potential for toxicity to reproduction, fertility and development. No mutagenic or clastogenic potential was observed.
The available data allows for an accurate hazard and risk assessment of the category and the category concept is applied for the assessment of environmental fate, environmental and human health hazards. Thus where applicable, environmental and human health effects are predicted from adequate and reliable data for source substance(s) within the group by interpolation to the target substances in the group (read-across approach) applying the group concept in accordance with Annex XI, Item 1.5, of Regulation (EC) No 1907/2006. In particular, for each specific endpoint the source substance(s) structurally closest to the target substance is/are chosen for read-across, with due regard to the requirements of adequacy and reliability of the available data. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across.
A detailed justification for the grouping of chemicals and read-across is provided in the technical dossier (see IUCLID Section 13).
Basic toxicokinetics
In accordance with Annex VIII, Column 1, Item 8.8 of Regulation (EC) 1907/2006 and with Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance (ECHA, 2008), assessment of the toxicokinetic behaviour of the substance Fatty acids, C12-18 and C18-unsatd., methyl esters (CAS No. 1234694-02-0) was conducted to the extent that can be derived from the relevant available information on physicochemical and toxicological characteristics. There are no studies evaluating the toxicokinetic properties of the substance available.
The substance Fatty acids, 16-18, methyl esters is an organic solid.It is poorly water soluble (< 1 mg/L) with a molecular weight of 270.46 – 298.51 g/mol, a log POW of 7.38 – 8.35 (trend analysis) and a vapour pressure of ≤ 0.008 Pa at 25 °C (trend analysis).
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, 2008).
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, 2008). As the molecular weight of Fatty acids, 16-18, methyl esters ranges between 270.46 – 298.51 g/mol, absorption of the molecule in the gastrointestinal tract is in general anticipated.
Absorption after oral administration is also expected when the “Lipinski Rule of Five” (Lipinski et al.(2001), refined by Ghose et al. (1999)) is applied to the substance Fatty acids, 16-18, methyl esters.
The log POW of 7.38 to 8.35 suggests that Fatty acids, 16-18, methyl esters is favourable for absorption by micelullar solubilisation, as this mechanism is of importance for highly lipophilic substances (log POW >4), who are poorly soluble in water (1 mg/L or less).
After oral ingestion, esters of methanol and fatty acids will undergo stepwise chemical changes in the gastro-intestinal fluids as a result of enzymatic hydrolysis. Methanol as well as the fatty acid will be formed, even though it was shown in-vitro that the hydrolysis rate of methyl oleate was lower when compared with the hydrolysis rate of the triglyceride Glycerol trioleate (Mattson and Volpenhein, 1972). The physico-chemical characteristics of the cleavage products (e.g. physical form, water solubility, molecular weight, log POW, vapour pressure, etc.) will 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, 2008). However, also for both cleavage products, it is anticipated that they will be absorbed in the gastro-intestinal tract. The highly lipophilic fatty acid will be absorbed by micellar solubilisation (Ramirez et a., 2001), whereas the methanol, being a highly water-soluble substance, will readily dissolve into the gastrointestinal fluids and pass through aqueous pores or be carried through the epithelial barrier (ICPS, 2002).
Exemplarily, experimental data of the structurally similar Ethyl Oleate (CAS No. 111-62-6) confirmed this assumption: The absorption, distribution, and excretion of 14C labelled Ethyl Oleate was studied in Sprague Dawley rats after a single, oral dose of 1.7 or 3.4 g/kg bw. It was shown that the test material was well (approximately 70–90%) absorbed (Bookstaff et al., 2003).
Overall, a systemic bioavailability of Fatty acids, 16-18, methyl esters and/or the respective cleavage products in humans is considered likely after oral uptake of the substance.
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, 2008). As the molecular weight of Fatty acids, 16-18, methyl esters ranges between 270.46 – 298.51 g/mol, a dermal absorption of the molecule cannot be excluded.
If the substance is a skin irritant or corrosive, damage to the skin surface may enhance penetration (ECHA, 2008). As Fatty acids, 16-18, methyl esters is not considered as skin irritating in humans, an enhanced penetration of the substance due to local skin damage can be excluded.
Based on QSAR calculations dermal absorption of 0.00030 mg/cm²/event (very low) was calculated for Fatty acids, C12-18, methyl esters (Danish EPA 2010). Based on this value, the substance has a low potential for dermal absorption.
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, 2008). As the water solubility of Fatty acids, 16-18, methyl esters is less than 1 mg/L, dermal uptake is likely to be (very) low.
Overall, the calculated low dermal absorption potential, the low water solubility, the high molecular weight (>100), the high log POW value and the fact that the substance is not irritating to skin implies that dermal uptake of Fatty acids, 16-18, methyl esters in humans is considered as very limited.
Inhalation:
Fatty acids, 16-18, methyl esters have a low vapour pressure of ≤ 0.008 Pa at 25 °C 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 not expected to be significant.
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 100μm have the potential to be inhaled. Particles with aerodynamic diameters below 50μm may reach the thoracic region and those below 15μm the alveolar region of the respiratory tract (ECHA, 2008). Lipophilic compounds with a log POW > 4, that are poorly soluble in water (1 mg/L or less) like Fatty acids, 16-18, methyl esters can be taken up by micellar solubilisation.
Overall, a systemic bioavailability of Fatty acids, 16-18, methyl esters in humans is considered likely after inhalation of aerosols with aerodynamic diameters below 15 μm.
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 implies that Fatty acids, 16-18, methyl esters may have the potential to accumulate in adipose tissue (ECHA, 2008).
However, as further described in the section metabolism below, esters of methanol and fatty acids will undergo esterase-catalysed hydrolysis, leading to the cleavage products methanol and Fatty acids, C16-18.
The log POW of the first cleavage product methanol is < 0, indicating a high solubility in water. Consequently, there is no potential for methanol to accumulate in adipose tissue. The second cleavage product, the fatty acids, 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.
Overall, the available information indicates that no significant bioaccumulation of the parent substance in adipose tissue is expected.
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, 2008).
Esters of methanol and fatty acids will undergo chemical changes as a result of enzymatic hydrolysis, leading to the cleavage products methanol and fatty acids, C16-18.
Methanol, a small, polar water-soluble substance (log POW < 0), will be distributed in aqueous fluids by diffusion through aqueous channels and pores.There is no protein binding and it is distributed poorly in fatty tissues (ICPS, 2002).
The fatty acids are also distributed in the organism and can be taken up by different tissues. They can be stored as triglycerides in adipose tissue depots or they can be incorporated into cell membranes (Masoro 1977).
Experimental data of the structurally similar Ethyl Oleate (CAS No. 111-62-6, ethyl ester of oleic acid) were regarded exemplarily. The absorption, distribution, and excretion of 14C labelled Ethyl Oleate was studied in Sprague Dawley rats after a single, oral dose of 1.7 or 3.4 g/kg bw. At sacrifice (72 h post-dose), mesenteric fat was the tissue with the highest concentration of radioactivity in both groups. The other organs and tissues had very low concentrations of test material-derived radioactivity (Bookstaff et al., 2003).
Overall, the available information indicates that the cleavage products, methanol and fatty acids, C16-18 will be distributed in the organism.
Metabolism:
Fatty acids, 16-18, methyl esters are hydrolysed to the corresponding alcohol (methanol) and fatty acid by esterases (Fukami and Yokoi, 2012), even though it was shown in-vitro that the hydrolysis rate of methyl oleate was lower when compared with the hydrolysis rate of the triglyceride Glycerol trioleate (Mattson and Volpenhein, 1972). Depending on the route of exposure, esterase-catalysed hydrolysis takes place at different places in the organism: After oral ingestion, esters of methanol and fatty acids will undergo chemical changes already in the gastro-intestinal fluids as a result of enzymatic hydrolysis. 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.
The first cleavage products, Fatty acids, C16-18, are 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 thecitric acid cycle. For the complete catabolism of unsaturated fatty acids such as oleic acid, an additional isomerization reaction step is required (see attached document). The omega- and alpha-oxidation, alternative pathways for oxidation, can be found in the liver and the brain, respectively (CIR, 1987).
The second cleavage product methanol, is slowly oxidized in the liver by the enzyme alcohol dehydrogenase (ADH) to formaldehyde, which itself is oxidized very rapidly by the enzyme aldehyde dehydrogenase (ALDH) to formic acid. Finally, formic acid is slowly metabolised to CO2 and H2O (ICPS, 2002).
Excretion:
For Fatty acids, 16-18, methyl esters, the main route of excretion is expected to be by expired air as CO2 after metabolic degradation. The second route of excretion is expected to be by biliary excretion with the faeces. For the cleavage product methanol, it is known that about thirty per cent of ingested substance is excreted unchanged by the respiratory tract; the kidney excretes less than 5% of unchanged methanol (ICPS, 2002).
Experimental data of the structurally similar Ethyl Oleate (CAS No. 111-62-6, ethyl ester of oleic acid) are regarded exemplarily. The absorption, distribution, and excretion of 14C labelled Ethyl Oleate was studied in Sprague Dawley rats after a single, oral dose of 1.7 or 3.4 g/kg bw. At sacrifice (72 h post-dose), mesenteric fat was the tissue with the highest concentration of radioactivity. The other organs and tissues had very low concentrations of test material-derived radioactivity. The main route of excretion of radioactivity in the groups was via expired air as CO2. Excretion of (14C) CO2 was rapid in the groups such that by 12 h after dosing 40-70% of the administered dose was excreted in expired air (consistent with beta-oxidation of fatty acids). The females had a higher percentage of radioactivity expired as CO2 than the corresponding males. A second route of elimination of radioactivity was via the feces. Faecal elimination of Ethyl Oleate appeared to be dose-dependent. At the dose of 1.7 g/kg bw, 7–8% of the administered dose was eliminated in the faeces. At the dose of 3.4 g/kg bw, approximately 20% of the administered dose was excreted in the faeces. Renal elimination was minimal, with approximately 2% of the radioactivity recovered in urine over 72 h post-dose for the groups (Bookstaff et al., 2003).
A detailed reference list is provided in the technical dossier (see IUCLID, section 13) and within CSR.
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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