Triisotridecyl benzene-1,2,4-tricarboxylate

Endpoint summary

Additional information

Justification for grouping of substances and read-across

The Polyfunctional acid ester (PFAE) aromatic category covers fatty alcohol esters of Benzene-1,2,4-tricarboxylic acid. The category contains both mono constituent and UVCB substances with fatty alcohol carbon chain lengths from C8-C13 (linear and iso-alcohols) building tri-esters with Benzene-1,2,4-tricarboxylic acid in variable proportions. A further surrogate substance of similar structure is included, namely a triester of Benzene-1,2,4-tricarboxylic acid with a C8 alcohol, but the alcohol moiety is branched (2-ethylhexyl).

Esters are generally produced by chemical reaction of an alcohol (e.g. Triisodecanol) with an organic acid (e.g. Benzene-1,2,4-tricarboxylic 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 alcohol 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). Tri-esters are the final products of esterification.

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 aromatic.

 

List of category members including CAS and molecular weight (range):

CAS	Chemical Name	Molecular weight	Carbon number in alcohol	Acid	Substance type
3319-31-1 (c)	Tris(2-ethylhexyl) benzene-1,2,4-tricarboxylate	546.78	C8branched	Benzene-1,2,4-tricarboxylic acid	M
90218-76-1 (former CAS No. 67989-23-5) (b)	1,2,4-Benzenetricarboxylic acid, mixed decyl and octyl triesters	546.78 - 630.94	C8; C10	Benzene-1,2,4-tricarboxylic acid	UVCB
36631-30-8	Triisodecyl benzene-1,2,4-tricarboxylate	630.94	C10iso	Benzene-1,2,4-tricarboxylic acid	M
94279-36-4 (a)	1,2,4-Benzenetricarboxylic acid, tri-C9-11-alkyl esters	588.86 - 673.02	C9; C11	Benzene-1,2,4-tricarboxylic acid	UVCB
72361-35-4	Triisotridecyl benzene-1,2,4-tricarboxylate	757.18	C13iso	Benzene-1,2,4-tricarboxylic acid	UVCB

(a) Category members 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.

(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 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 three mono-functional fatty alcohols with 1,2,4-benzene tricarboxylic acid. The fatty alcohol moiety comprises chain lengths from C8-C13 inlcuding linear and iso-chains (branched in case of the surrogate substance) and the acid moiety is 1,2,4-benzene tricarboxylic acid (trimellitic acid) and common in for all category members resulting in tri-esters; 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 an alcohol with the aromatic tricarboxylic acid. Esterification is, in principle, a reversible reaction (hydrolysis). Thus, the alcohol and the tricarboxylic acid moieties are simultaneously precursors and breakdown products of the category members. Taken into account the high MW, the high log Pow and the limited water solubility absorption of the substance is possible but limited for any category member. For the purpose of grouping of substances, stepwise enzymatic hydrolysis via di- and mono-ester in the gastrointestinal tract and/or liver after absorption is identified as the biological process, by which the breakdown of the category members result in structurally similar chemicals. However, available data on a category member indicate that the substance will only be partly absorbed. If absorbed, trimellitic acid might be enzymatically degraded via β-oxidation, the degradation pathway of fatty acids following hydrolysis and cleavage of the aromatic ring. Alternative oxidation pathways (alpha- and omega-oxidation) are available and are relevant for degradation of branched fatty acids. The fatty alcohol is, in general, likewise enzymatically oxidized to the corresponding carboxylic acid, which can be further degraded by β-oxidation (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 in regard to physicochemical, environmental fate, ecotoxicological and toxicological properties. In case of the surrogate substance, the applicability of the read-across principle does not include all endpoints, as the short-chain branched alcohol moiety is known to affect the toxicological behaviour of the substance at the endpoint toxicity to reproduction/ developmental toxicity. Therefore a read across to the surrogate substance at this endpoint is considered unsuitable. A detaild justification is provided in the endpoint summary toxicity to reproduction.

 a) Physicochemical properties:

The molecular weight of the category members ranges from 546.78 to 757.18 g/mol. All category members are non-volatile liquids at room temperature with vapour pressures < 0.001 kPa. The octanol/water partition coefficients of the category members are in the range of 10.6 to 18.96 and the water solubility is very low (< 0.05 mg/L).

b) Environmental fate and ecotoxicological properties:

Considering the low water solubility (< 0.05 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 enhanced ultimate 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 (< 0.001 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 and effects on terrestrial organisms is negligible. Moreover, due to the low water solubility, complete environmental biodegradation in a short time period and low absorption potential in biota 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 aromatic category members), a relevant uptake and bioaccumulation in aquatic organisms is not expected. Furthermore, absorbed molecules of the category members will be metabolized and the metabolites will be excreted.

c) Toxicological properties:

The toxicological properties show that all category members have similar toxicokinetic behaviour (partial hydrolysis of the ester bond before absorption followed by absorption and metabolism of the breakdown products) and that the constant pattern consists in a lack of potency change of properties across the category, explained by the common metabolic fate of all trimellitate esters independently of the fatty alcohol chain length. Thus, 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 of low toxicity after repeated oral exposure and not mutagenic or clastogenic and have shown no indication for reproduction toxicity or effects on intrauterine development.

Effects on male fertility (change in sperm parameters) seen in a disregarded study with the surrogate substance (CAS 3319-31-1) is presumably due to the branching of the short-chain alcohol moiety (2-ethylhexanyl) and not considered relevant for the category members.

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).

Endpoint specific data matrix:

ID No.	CAS	Phototransformation in air [DT50, 24 h day]	Hydrolysis [DT50, pH 7]	Biodegradation: screening tests	BCF / BAF [L/kg]	Adsorption / Desorption [log Koc]
#2	90218-76-1	--	--	Experimental result: 301B, 20.7 - 45% in 28 days Not readily biodegradable 71.4 – 78% in 40-50 days Enhanced ultimately biodegradable	--	Experimental result: 121 log KOC > 5.67
#4	94279-36-4 (a)	(Q)SAR: 8.87 - 11.02 h	> 350 d	RA: CAS 90218-76-1	(Q)SAR: 0.89/0.89-0.91 (Arnot/Gobas)	(Q)SAR : log Koc > 5 (MCI method) RA : CAS 90218-76-1
#5	72361-35-4	(Q)SAR: 7.423 h	> 102 d	RA:CAS 90218-76-1	Q)SAR: 0.89/0.89 (Arnot/Gobas)	(Q)SAR : log Koc > 5 (MCI method) RA : CAS 90218-76-1

(a) Category members subject to registration are indicated in bold font. Only for these substances a full set of experimental results and/or read-across is given.

(b) Substances not subject to registration are indicated in normal font. Lack of data for a given endpoint is indicated by “--“.

 

Environmental fate and pathways

Partitioning of substances into different environmental compartments depends mainly on their physico-chemical properties. Based on experimental studies all members of the Polyfunctional Fatty acid Ester (PFAE) aromatic category can be considered as not readily biodegradable according to OECD criteria (20.7 - 45% biodegradation after 28 days). However, based on these biodegradation studies the category members can be considered as enhanced ultimately biodegradable (71.4 - 78% biodegradation in 40 - 50 days). Therefore, the PFAE aromatic 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 half-lives (DT50) of >1 yr at pH 7. Considering the low water solubility (< 0.05 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 aromatic category members would be soil and sediment. However, the substances are enhanced ultimately biodegradable and highly sorptive, based on calculated estimation, and are thus expected to be eliminated and adsorbed to sewage sludge in sewage treatment plants to a high extent. Release to surface waters, and thereby exposure of sediment is therefore very unlikely. 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 values (VP: < 0.001 Pa). Accumulation in air and the subsequent transport to other environmental compartments is thus not anticipated. However, if released into air, all category members are susceptible to indirect photodegradation by reaction with OH-radicals with a DT50: < 24 h (AOPWIN v1.92). Due to the low water solubility, complete environmental biodegradation in a short time period and low absorption potential in biota 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 aromatic category members), a relevant uptake and bioaccumulation in aquatic organisms is not expected. Furthermore, absorbed molecules of the category members will be metabolized and the metabolites will be excreted. This is supported by low BCF values calculated for all category members (BCF 0.89 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.