Fatty acids, C8-10, mixed esters with adipic acid and trimethylolpropane

Endpoint summary

Additional information

Justification for grouping of substances and read-across

The category covers fatty acid polyesters of polyols (Trimethylolpropane (TMP) or Pentaerythritol (PE)) mixed with adipic acid. The category contains UVCB substances with fatty acid carbon chain lengths from C8-C18 (even-numbered, including linear saturated and unsaturated chains) building mono-, di-,tri- or higher esters with TMP or PE respectively in variable proportions.

Fatty acid esters are generally produced by chemical reaction of an alcohol (in this case Polyol e.g. Propylidynetrimethanol) with an organic fatty acid (e.g. oleic 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). The dicarboxylic acid adipic acid functions as a crosslinking agent forming diesters with polyols and this scaffold is esterified with fatty acids. Oligomeric structures with high molecular weights (MW>>500 g/mol) are thus built.

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 mixed and branched.

PFAE mixed and branched category members include:

ID#	CAS	EC	Chemical Name	Fatty acids	Di-carboxylic acid (cross-link)	Polyol	MW
1	95912-89-3 (a)	306-085-3	Fatty acids, C8-10, mixed esters with adipic acid and trimethylol-propane	C8-C10	Adipic acid	TMP	512.78 – 995.46
2	91001-61-5	292-832-8	Fatty acids, C16-18 and C18-unsatd., mixed esters with adipic acid and trimethylol-propane	C16, C18, C18 unsatd,	Adipic acid	TMP	849.46 – 1444.31
3	-	921-836-0	Mixed esters of fatty acid C16 and C16-C18-unsatd. with adipic acid and pentaerythritol	C16, C16- C18 unsatd,	Adipic acid	PE	1081.72 – 1969.08
4	78-16-0 (b)	201-089-0	2-ethyl-2-[[(1-oxoheptyl)oxy]methyl]propane-1,3-diyl bisheptanoate	C7	-	TMP	470.68

TMP = Propylidynetrimethanol / Trimethylolpropane; PE = Pentaerythritol

(a) Category members subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in bold font.

(b) 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 toxicological properties by read-across on the same basis of structural similarity and/or mechanistic reasoning as described below for the present category.

 

Category specific similarities/trends:

Grouping of substances into this category is based on:

(1) common functional groups: all members of the respective category are esters of a polyfunctional alcohol with one or more carboxylic fatty acid(s) chain(s) and adipic acid (cross-linking agent) resulting in oligomeric structures. The alcohol moiety is either TMP or PE, which only differ by one hydroxyl-group. The carboxylic acid moiety comprises on one hand fatty acids with carbon chain lengths from C8-C18 (even-numbered) including saturated and unsaturated chains and on the other hand the dicarboxylic acid adipic acid; both acid components are bound to the alcohol with the latter acting as cross-linking agent, resulting in polyol polyesters. These Polyol polyesters may have multiple ester linkages and may include mixed esters derived from different carbon-length fatty acid mixtures; 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 fatty acids and adipic acid. Esterification is, in principle, a reversible reaction (hydrolysis). Thus, in theory the alcohol, dicarboxylic acid and fatty acid moieties are simultaneously precursors and breakdown products of the category members. Taken into account the high MW resulting in a very complex structure, the high log Pow and the very limited water solubility absorption of the substance is highly unlikely for any category member. Enzymatic hydrolysis in the gastrointestinal tract and/or liver - usually identified as the biological process, by which the breakdown of esters takes place - is highly unlikely for PFAE mixed and branched category members. The category members have a complex structure consisting of several mixed polyols linked with adipic acid that is not anticipated to fit into the binding pocket of e.g. pancreatic lipase which hydrolyses emulsified triacylglycerols in the diet. The ester bond is thus not available to catalytic center of the enzyme. (refer to Toxicokinetics for details);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 physicochemical, environmental fate, ecotoxicological and toxicological properties. For those individual endpoints showing a trend, the pattern in the changing of potency is clearly and expectedly related to the length of the fatty acid chains and the degree of substitution of the polyol:

a) Physicochemical properties:

The molecular weight of the category members ranges from 512.77 to 1969.08 g/mol. This range represents structures completely esterified and cross linked with one adipic acid unit and is taken as the lower limit of molecular weight and size for the different substances. The physical appearance is related to the chain length of the fatty acid moiety, the degree of saturation and the number of ester bonds. All substances are liquid. All category members a non-volatile (vapour pressure: <0.01 Pa). The octanol/water partition coefficient increases with increasing fatty acid chain length and number of ester bonds, ranging from log Pow = 10.64 for the C8 TMP triester component for CAS 95912-89-3 to log Pow = 28.35 for the C16 PE tetraester component of EC 921-836-0 (calculated values). These are values for the smallest components of all substances in the category. As log Pow >10 exceeds the applicability domain for the (Q)SAR model, log Pow is >10 is given for all category members. The water solubility for all substances is <1 mg/L, for Fatty acids, C8-10, mixed esters with adipic acid and trimethylolpropane (CAS 95912‑89‑3) the water solubility is determined to be even lower (<0.05 mg/L).

b) Environmental fate and ecotoxicological properties:

Considering the low water solubility (<1 mg/L) and the potential for adsorption to organic soil and sediment particles (log Koc >5), the main compartments for environmental distribution are expected to be the soil and sediment. Nevertheless, persistency in these compartments is not expected since all members of the category are readily biodegradable and are thus expected to be eliminated in sewage treatment plants to a high extent. Release to surface waters, and thereby exposure of sediment, is very unlikely. Thus, the soil is expected to be the major compartment of concern. Nevertheless, the category members are expected to be metabolised by soil microorganisms. Evaporation into air and the transport through the atmosphere to other environmental compartments is not expected since the category members are not volatile based on the low vapour pressure (<0.01 Pa).

All members of the category did not show any effects on aquatic organisms in the available acute and chronic tests representing the category members up to the limit of water solubility. Moreover, bioaccumulation is assumed to be low since due to the molecular weight, size and structural complexity of the molecules of the category members absorption is not likely and ingested molecules will be excreted unchanged. 

c) Toxicological properties:

The toxicological properties show that all category members have similar toxicokinetic behaviour (very high MW, complex structure, limited water solubility, high log Pow) and that the constant pattern consists in a lack of potency change of properties across the category, explained by the very low potential for absorption and thus systemic availability of all mixed Polyol polyesters with adipic acid independently of the fatty acid chain length. Therefore, considering all available evidence and expert judgement no category member showed acute oral, dermal or inhalation toxicity, no skin irritation, eye irritation or sensitizing properties and are not mutagenic. Based on the very limited potential for absorption repeated dose toxicity, reproductive toxicity and developmental toxicity are not expected and further tests are not considered necessary.  

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 read across data within the group applying the group concept in accordance with Annex XI, Item 1.5, of Regulation (EC) No 1907/2006.

A detailed justification for the grouping of chemicals and read-across is provided in the technical dossier (see IUCLID Section 13).

Endpoint specific data matrix:

ID #	Identifier	Phototransformation in air [DT50, 24 h day]	Hydrolysis [DT50, pH 7]	Biodegradation: screening tests	BCF / BAF [L/kg]	Adsorption / Desorption [log Koc]
1	CAS 95912-89-3 (a)	(Q)SAR: 10.33 - 13.37 h	>1 yr	Experimental result: 301B,78.1 - 84.7% in 28 days Readily biodegradable	(Q)SAR: 0.89 – 0.91/0.89-0.91 (Arnot/Gobas)	(Q)SAR: log Koc >5 (MCI method)
2	CAS 91001-61-5	(Q)SAR: 1.52 – 6.14 h	>1 yr	Experimental result: 301B, 79.5% in 28 days Readily biodegradable	(Q)SAR: 0.89/0.89 (Arnot/Gobas)	(Q)SAR: log Koc >5 (MCI method)
3	EC 921-836-0	(Q)SAR: 1.15 – 4.7 h	>1 yr	Experimental result: 301B, 69% in 28 days Readily biodegradable	(Q)SAR: 0.89/0.89 (Arnot/Gobas)	(Q)SAR: log Koc >5 (MCI method)

(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.

Environmental fate and pathways

Partitioning of substances into the different environmental compartments depends mainly on their physico-chemical properties. Several experimental studies confirmed that all members of the Polyfunctional Fatty acid Ester (PFAE) mixed and branched category are readily biodegradable according to the OECD criteria (69 – 84.7% biodegradation after 28 d). Therefore, the category members will not be persistent in the environment. The degradation via abiotic hydrolysis is not considered to be a relevant degradation pathway in the environment since QSAR results using HYDROWIN v2.00 resulted in a half-life (DT50) of >1 yr at pH 7. Considering the low water solubility (< 1 mg/L) and the high potential for adsorption to organic soil and sediment particles (log Koc: > 5, MCI method, KOCWIN v2.00), the main target compartments for the PFAE mixed and branched category members would be soil and sediment. However, the substances are readily biodegradable and highly sorptive, based on calculated estimation, and are thus expected to be eliminated in sewage treatment plants to a high extent. Release to surface waters, and thereby exposure of sediment is therefore very unlikely. In soil, members of the PFAE mixed and branched category are expected to be rapidly degraded by microorganisms. Evaporation into air and the transport through the atmospheric compartment is not expected since the category members are not volatile based on the low vapour pressure (VP: < 0.01 Pa). Accumulation in air and the subsequent transport to other environmental compartments is not anticipated. However, if released into air, all category members are susceptible to indirect photodegradation by OH-radicals with a DT50: < 24 h (AOPWIN v1.92). Due to the low water solubility, rapid environmental biodegradation and low absorption potential due to the high molecular weight of the substances which significantly reduces the absorption due to steric hindrance to cross biological membranes of the PFAE mixed and branched category members, a relevant uptake and bioaccumulation in aquatic organisms is not expected. This is supported by low BCF values calculated for all category members (BCF 0.89-0.91 L/kg; BCFBAF v3.01; Arnot-Gobas, including biotransformation, upper trophic).

A detailed reference list is provided in the technical dossier (see IUCLID, section 13) and within CSR.