Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 618-295-5 | CAS number: 897626-46-9
- 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
![](https://poisoncentres.echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Endpoint summary
Administrative data
Link to relevant study record(s)
Description of key information
Key value for chemical safety assessment
- Bioaccumulation potential:
- low bioaccumulation potential
Additional information
Justification for grouping of substances
The PFAE Linear (Polyfunctional Aliphatic Ester) category consists of 16 substances, well-defined mono-constituent substances as well as related UVCB substances, respectively with varying fatty alcohol chain lengths and branching. The distinguishing feature of this category of chemicals is that they are diester derivatives of common dicarboxylic acids: namely adipic (C6), azelaic (C9) and sebacic (C10) acids. The alcohol portion of the diesters generally falls in the C3-C20 carbon number range, including linear and branched, even and odd numbered alcohols.
Carboxylic acid esters are generally produced by chemical reaction of an alcohol with an organic 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). Diesters are the final products of esterification of alcohols (e.g. octanol) with a dicarboxylic organic acid (e.g. adipic acid).
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 PFAE linear.
List of category members including CAS and molecular weight (range):
ID# |
CAS |
Chemical name |
Molecular weight |
Carbon number in alcohol |
Carbon number in acid |
Substance type |
1 |
6938-94-9 (a) |
Diisopropyl adipate |
230.3 |
C3 iso |
C6 |
M |
2 |
105-99-7 |
Dibutyl adipate |
258.35 |
C4 |
C6 |
M |
3 |
110-33-8 |
Dihexyl adipate |
314.46 |
C6 |
C6 |
M |
4 |
1330-86-5 |
Diisooctyl adipate |
370.57 |
C8 iso |
C6 |
M |
5 |
123-79-5 (b) |
Dioctyl adipate |
370.57 |
C8 |
C6 |
M |
6 |
103-23-1 |
Bis(2-ethylhexyl) adipate / DEHA |
370.64 |
C8 branched |
C6 |
M |
7 |
68515-75-3 |
Hexanedioic acid, di-C7-9-branched and linear alkyl esters |
342.52-398.63 |
C7-C9 linear and branched |
C6 |
UCVB |
8 |
33703-08-1 |
Diisononyl adipate |
398.63 |
C9 iso |
C6 |
UVCB |
9 |
16958-92-2 |
Bis(tridecyl) adipate |
454.73-566.94 |
C11-C15 |
C6 |
UVCB |
10 |
85117-94-8 |
Bis(2-octyldodecyl) adipate |
707.2 |
C20 branched |
C6 |
M |
11 |
103-24-2 |
Bis(2-ethylhexyl) azelate |
412.65 |
C8 branched |
C9 |
M |
12 |
897626-46-9 |
Bis(2-octyldodecyl) azelate |
749.28 |
C20 branched |
C9 |
M |
13 |
7491-02-3 |
Diisopropyl sebacate |
286.41 |
C3 iso |
C10 |
M |
14 |
109-43-3 |
Dibutyl sebacate |
314.47 |
C4 |
C10 |
M |
15 |
122-62-3 |
Bis(2-ethylhexyl) sebacate |
426.69 |
C8 branched |
C10 |
M |
16 |
69275-01-0 |
Bis(2-octyldodecyl) sebacate |
763.34 |
C20 branched |
C10 |
M |
(a) Category members OR substances subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in bold font.
(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.
Category specific similarities/trends:
Grouping of substances into this category is based on:
(1) common functional groups: all members of the category PFAE linear are diester derivatives of the common saturated diacids: namely adipic (C6), azelaic (C9) and sebacic (C10) acid. The alcohol portion of the diesters generally falls in the C3-C20 carbon number range, including linear and branched alcohols; and
(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 dicarboxylic acid. Esterification is, in principle, a reversible reaction (hydrolysis). Thus, the fatty alcohol and dicarboxylic 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 (Takahashi et al., 1981). Following hydrolysis, the fatty alcohol is, in general, enzymatically oxidized to the corresponding carboxylic acid, which can be further degraded by β-oxidation. Alternative oxidation pathways (alpha- and omega-oxidation) are available and are relevant for degradation of branched fatty acids (for further information please see chapter 7.1 of the technical dossier); and
(3) constant pattern in the changing of the potency of the properties across the category: the available data show similarities and trends within the category in regard to (a) physicochemical, (b) environmental fate, ecotoxicological and (c) toxicological properties. For those individual endpoints showing a trend (d), the pattern in the changing of potency is clearly and expectedly related to the carbon chain length of the dicarboxylic acid and the carbon chain length and/or branching of the alcohol.
a) Physicochemical properties:
The molecular weight of the category members ranges from 230 g/mol (CAS 6938-94-9, Diisopropyl adipate) to 763 g/mol (CAS 69275-01-0, Bis(2-octyldodecyl) azelate). Category substances are characterized with low melting points: they are liquid under ambient conditions. All category substances decompose before boiling and they are non-volatile. Calculated vapour pressures exceed 0.01 Pa (at 20 °C) only for two compounds with the lowest molecular weight: Diisopropyl adipate (MW = 230 g/mol, VP = 0.26 Pa) and Dibutyl adipate (MW = 258 g/mol, VP = 0.02 Pa – both experimental and calculated). The same two compounds are soluble in amounts exceeding 10 mg/L (i.e: 180 mg/L and 35 mg/L, respectively). The remaining substances with <10 mg/L are very poorly soluble or insoluble in water. The calculated octanol/water partition coefficient increases with molecular weight accordingly: from log Pow = 3.2 (Diisopropyl adipate) to log Pow = 21.4 (Bis(2-octyldodecyl) azelate).
b) Environmental fate and ecotoxicological properties:
All members of the category are readily biodegradable according to the OECD criteria. Therefore, the category members will not be persistent in the environment. The abiotic degradation via hydrolysis is not considered to be a relevant degradation pathway in the environment. Relatively good water soluble (approximately > 10 mg/L) members of the category exhibit log Kow values < 5. Substances with log Kow < 5 are expected to distribute in the aquatic, sediment and soil compartment. In contrast, substances with log Kow values > 5, will mainly distribute into soil and sediment exclusively. Nevertheless, since all members of the category are readily biodegradable, they will not be persistent in the terrestrial environment. Based on the rapid environmental biodegradation and metabolisation via enzymatic hydrolysis, relevant uptake and bioaccumulation in aquatic organisms is not expected. Enzymatic breakdown will initially lead to the free dicarboxylic acid and the free alcohol. From literature it is well known, that these hydrolysis products will be metabolised and excreted in fish effectively (see expert statement on bioaccumulation chapter 5.3 of the technical dossier). This is supported by low calculated BCF values calculated for all category members (BCF < 1 - 29 L/kg ww; BCFBAF v3.01; Arnot-Gobas, including biotransformation, upper trophic).
Based on the experimental data, the majority of category members exhibit no acute or chronic toxicity to aquatic organisms. Only two “water soluble” esters with Adipic acid (C6) as dicarboxylic acid component and short chain alcohols, exhibit toxic or harmful effects (CAS 105-99-7, Dibutyl adipate and CAS 6938-94-9, Diisopropyl adipate). Due to their rapid biodegradability and rapid metabolization, no adverse effects are anticipated in sediment and soil organisms. This assumption is supported by three short term tests to earthworm for Bis(2-ethylhexyl) adipate (CAS 103-23-1), Dibutyl adipate (CAS 105-99-7) and Bis(tridecyl) adipate (CAS 16958-92-2) showing LC50 values above 800 mg/kg soil dw.
c) Toxicological properties:
The toxicological properties show that all category members have similar toxicokinetic behaviour (enzymatic hydrolysis of the ester bond leading to the corresponding dicarboxylic acid and alcohol, then absorption and further metabolism to polar products that are excreted in the urine or exhalation as CO2). There is consistently low toxicity among the category members which can be explained by the common metabolic fate of all aliphatic diesters, independent of the lengths of the dicarboxylic acid backbone (C6, C9 or C10) or the alcohol side chains (C3 to C20). Thus, considering all available evidence and expert judgement the category members showed no acute oral, dermal or inhalation toxicity, no skin irritation, eye irritation or sensitizing properties, no human hazard for systemic toxicity after repeated oral, inhalative and dermal exposure and are not mutagenic or clastogenic and have shown no relevant reproduction toxicity and have no effect on intrauterine development.
In order to avoid the need to test every substance for every endpoint, the category concept is applied for the assessment of environmental fate and 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).
Toxikokinetics, metabolism and distribution:
CAS 897626-46-9
Basic toxicokinetics
There are no studies available in which the toxicokinetic behaviour of Bis(2-octyldodecyl) azelate (CAS 897626-46-9) 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, 2012), assessment of the toxicokinetic behaviour of the substance Bis(2-octyldodecyl) azelate 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, 2012) and taking into account further available information on the PFAE linear category.
Bis(2-octyldodecyl) azelate is a diester of two 2-octyldodecyl alcohols and azelaic acid (nonanedioic acid) and meets the definition of a mono-constituent substance based on the analytical characterization.
Bis(2-octyldodecyl) azelate is liquid at room temperature and has a molecular weight of 749.28 g/mol and a water solubility of < 0.0004 mg/L at 20 °C (Lange, 2007). The log Pow is calculated to be > 5.7 (Frischmann, 2008) and the vapour pressure is estimated to be < 1.9E-3 Pa at 20 °C (Kintrup, 2008).
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, 2012).
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, 2012). As the molecular weight of Bis(2-ethylhexyl) azelate is 749.28 g/mol, absorption of the molecule in the gastrointestinal tract is limited.
Absorption after oral administration of Bis(2-octyldodecyl) azelate is expected to be limited when the “Lipinski Rule of Five” (Lipinski et al., 2001; refined by Ghose et al. 1999) is applied, as the molecular weight, the log Pow and the total number of atoms are above the given range.
The log Pow > 5.7 suggests that Bis(2-octyldodecyl) azelate is favourable for 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) (ECHA, 2012).
After oral ingestion, the members of the PFAE linear category undergo stepwise hydrolysis of the ester bonds by gastrointestinal enzymes (Lehninger, 1970; Mattson and Volpenhein, 1972). The respective alcohol as well as the dicarboxylic acid is formed. 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, 2012). However, also for both cleavage products, it is anticipated that they are absorbed in the gastro-intestinal tract. In case of long carbon chains and thus rather low water solubility by micellar solubilisation (Ramirez et al., 2001), and for small and water soluble cleavage products by dissolution into the gastrointestinal fluids (ECHA, 2012).
Overall, a systemic bioavailability of Bis(2-octyldodecyl) azelate 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, 2012). As the molecular weight of Bis(2-octyldodecyl) azelate is 749.28 g/mol, 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, 2012). As Bis(2-octyldodecyl) azelate is not skin irritating in humans, enhanced penetration of the substance due to local skin damage can be excluded.
Based on a QSAR calculated dermal absorption a value of 0.000009 mg/cm²/event (very low) was predicted for Bis(2-octyldodecyl) azelate (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, 2012). As the water solubility of Bis(2-octyldodecyl) azelate is less than 1 mg/L, dermal uptake is likely to be (very) low.
Overall, the low water solubility, the high molecular weight (>500), the high log Pow value and the fact that the substance is not irritating to skin implies that dermal uptake of Bis(2-octyldodecyl) azelate in humans is considered as very limited.
Inhalation:
Bis(2-octyldodecyl) azelate has a low vapour pressure of 0.0019 Pa at 20 °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 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, 2012). Lipophilic compounds with a log Pow > 4, that are poorly soluble in water (1 mg/L or less) like Bis(2-octyldodecyl) azelate can be taken up by micellar solubilisation.
Overall, a systemic bioavailability of Bis(2-octyldodecyl) azelate 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 Bis(2-octyldodecyl) azelate may have the potential to accumulate in adipose tissue (ECHA, 2012).
However, as further described in the section metabolism below, esters of alcohols and dicarboxylic acids undergo esterase-catalysed hydrolysis, leading to the cleavage products 2-octyldodecanol and nonanedioic acid.
The first cleavage product 2-octyldecanol is a fatty alcohol of low water solubility. However, fatty alcohols have limited potential for retention or bioaccumulation as they are efficiently metabolised (OECD SIDS, 2006). The second cleavage product, azelaic acid, has a log Pow value of 1.57 and is soluble in water (HSDB, 2011). Consequently, accumulation in adipose tissue is not likely.
This assumption is supported by results from studies performed with the structurally similar substance Bis(2-ethylhexyl) adipate (CAS 103-23-1) indicating no potential for bioaccumulation (Elcombe, 1981; Takahashi et al., 1981).
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, 2012).
Bis(2-octyldodecyl) azelate undergoes chemical changes as a result of enzymatic hydrolysis, leading to the cleavage products 2-octyldodecanol and azelaic acid.
Aliphatic fatty alcohols, like 2-octyldodecanol, are widely distributed within the body and efficiently eliminated (OECD SIDS, 2006). Azelaic acid will be distributed in aqueous compartments.
As described in the following chapter, the distribution of Bis(2-ethylhexyl) adipate (DEHA, CAS 103-23-1), a structurally similar substance, was assessed in rats treated with the radioactive labeled substance. Relatively high levels of radioactivity appeared in the liver, kidney, blood, muscle and adipose tissue apart from the stomach and intestine. All other tissues contained very little residual radioactivity. In liver, kidney, testicle and muscle, the amount of residual radioactivity reached a maximum in the first 6 - 12 h and reduced to less than 50% at 24 h. In other tissues the radioactivity declined with time after 6 h. The blood contained about 1% of the radioactivity after 6-12 h and then decreased to undetectable levels by the end of 2 days. It was also evident that total radioactivity in the tissues examined was about 10% after 24 h of dosing and it decreased to about 2% and 0.5% after 48 h and 96 h, respectively. From these results, it can be concluded that the elimination of radioactivity from tissues and organs is very rapid and there is no specific organ affinity under these experimental conditions (Takahashi et al., 1981).
Overall, the available information indicates that Bis(2-octyldodecyl) azelate and its cleavage products, 2-octyldodecanol and azelaic acid, will be distributed within the organism.
Metabolism
Dicarboxylic acid esters are expected have the same metabolic fate as fatty acid esters. Esters of fatty acids are hydrolysed to the corresponding alcohol and carboxylic acid by esterases (Fukami and Yokoi, 2012; Lehninger, 1970). Depending on the route of exposure, esterase-catalysed hydrolysis takes place at different places in the organism: After oral ingestion, esters of alcohols and dicarboxylic acids likewise undergo stepwise 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.
In the first step of hydrolysis, the monoester is produced that is further hydrolysed to the alcohol and the dicarboxylic acid. During the first step of alcohol metabolism of the biotransformation the alcohols are oxidized to the corresponding carboxylic acids, followed by a stepwise elimination of C2-units in the mitochondrial beta-oxidation process (OECD SIDS, 2006). The second cleavage product, azelaic acid, is partly metabolized by beta oxidation. After 8 hr, 6% of the radioactivity from a tracer dose of [14C]azelaic acid to rats was recovered as 14CO2. Successive cleavage by beta-oxidation results in the formation of pimelic and glutaric acids and subsequently malonyl-CoA and acetyl-CoA. Thus, azelaic acid is incorporated into fatty acid biosynthesis and the citric acid cycle (HSDB, 2011).
Experimental data of the structurally similar di-2-ethylhexyl adipate (DEHA, CAS 103-23-1) are regarded exemplarily. The elimination, distribution and metabolism were assessed in rats according to a protocol similar to OECD Guideline 417 (Takahashi et al., 1981). 14C-DEHA (labelled at the carbonyl carbon of adipic acid) in DMSO was administered to male Wistar rats by oral gavage. Adipic acid was found as main metabolite in urine in a short time and its excretion reached 20-30% of the administered dose within 6 h. In blood it was found at 1% and in liver at 2-3%; mono-(2-ethylhexyl) adipate (MEHA) was the second metabolite found, but to a very less extent. Thus, cleavage of parent substance was shown in vivo within 6 hours into adipic acid (20-30% in urine, 1% in blood, 2-3% in liver) and MEHA to a lesser extent. From these results, it is clear that orally ingested DEHA is rapidly hydrolyzed to MEHA and adipic acid which is the main intermediate metabolite.
In vitro, DEHA was hydrolysed to MEHA and adipic acid by tissue preparations from liver, pancreas and small intestine. When testing MEHA, the monoester was more rapidly hydrolysed to adipic acid than DEHA by these preparations, and the intestinal preparation was the most active one among them (Takahashi et al., 1981).
In another in vivo study in rats and mice, 2-ethylhexanoic acid (EHA), 2-ethyl-5-hydroxyhexanoic acid and 2-ethylhexan-1,6-dioic acid and their glucuronides were found in urine after administration of DEHA (labelled at the side chain). In monkey, however, large amounts of MEHA-glucuronide and 2-ethylhexanol glucuronide were excreted and only a very small proportion of the dose was converted to EHA and other downstream metabolites (Elcombe, 1981).
Overall, Bis(2-octyldodecyl) azelate is hydrolyzed and the cleavage products are metabolized by beta oxidation and/or glucuronidation.
Excretion
For Bis(2-octyldodecyl) azelate, the main route of excretion is expected to be by expired air as CO2 after metabolic degradation (beta-oxidation) and via biliary excretion with the faeces. For the cleavage products, the main routes are renal excretion via the urine and exhalation as CO2. Azelaic acid is extensively and rapidly excreted via the urine. Approximately 60% of an oral-dose is excreted unchanged in the urine within 12 hours (HSDB, 2011).
Experimental data of the structurally similar DEHA (CAS 103-23-1) are available. In monkeys, large amounts of MEHA-glucuronide and 2-ethylhexanol glucuronide were detected in urine (Elcombe, 1981). In in vivo and in vitro studies with DEHA, adipic acid was found as main metabolite in urine in a short time and its excretion reached 20-30% of the administered dose within 6 h. In rats, excretion within 24 h amounted to 86% of the administered dose and almost all the dose was excreted in 48 h. The greater part of the excretion was recovered in breath and urine; excretion in faeces was small (Takahashi et al., 1981).
Thus, renal excretion after glucuronidation and exhalation as CO2 are the most relevant routes of excretion of the substance itself or its metabolites.
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.
![ECHA](/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/echa_logo.png)