Fatty acids, C16-18 and C18-unsatd., hexaesters with dipentaerythritol

Bioaccumulation: aquatic / sediment

Description of key information

Polyol esters are expected to have a low potential for bioaccumulation.

Additional information

Experimental data on bioaccumulation of Fatty acids, C16-18 and C18-unsatd., hexaesters with dipentaerythritol (CAS 68604-38-6) is not available. The evaluation of the bioaccumulation potential of the substance is therefore based on a Weight of Evidence (WoE), combining all available related data. This is in accordance to the REACh Regulation (EC) No 1907/2006, Annex XI General rules for adaptation of the standard testing regime set out in Annexes VII to X, 1.2, to cover the data requirements of Regulation (EC) No. 1907/2007 Annex IX and X (Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance, R.7.11.5.3, page 123 ff (ECHA, 2012)).

Environmental behaviour

The bioaccumulation potential of a substance is driven by the physic-chemical properties of the substance triggering the bioavailability as well as by metabolism and excretion. The bioavailability of the substance is expected to be low. Though the substance has a high calculated partition coefficient (log Kow of main components: 42.27 - 46.87, KOWWIN v1.68; Blum, 2011) indicating the potential to bioaccumulate a significant accumulation is not expected based on the environmental fate and on BCF/BAF calculation.The calculated log Koc values of the main components of > 5 indicates that the substance will adsorb to suspended organic particles, dissolved organic matter and to some degree biota in the aquatic environment (Jaffé, 1991).A potential uptake of the substance by organisms of the pelagic zone is expected to occur mainly via food ingestion since the substance may adsorb to solid particles. Benthic or sediment-dwelling organisms may take the substance up by ingestion of contaminated sediment.
Despite that the substance is not readily biodegradable elimination in sewage treatment plants is expected due to the high adsorption potential and the very low water solubility. Insoluble substances are largely removed in the primary settling tank and fat trap during the clarification and sedimentation process of waste water treatment (according to the Guidance on information requirements and chemical safety assessment, Chapter R7.b (ECHA, 2012)). Only small amounts of the substance may enter the secondary treatment and thus get in contact with activated sludge. Due to the high log Koc calculated for the substance components an extensive adsorption to sewage sludge is expected. Thus the substances is expected to be removed from the water column to a significant degree (Guidance on information requirements and chemical safety assessment, Chapter R.7a (ECHA, 2012)). However, when released to the aquatic environment the concentration in the water phase will be further reduced by potential of adsorption to solid particles and to sediment. Thus a significant uptake of the substance by aquatic organisms through the water phase is not expected.Considering this, one can assume that the availability of the substance in the aquatic environment is generally low, which reduces the probability of uptake by aquatic organisms (e.g., see McKim et al, 1984; Björk, 1995; Haitzer et al., 1998).
If the substance is taken up by ingestion, absorption ofFatty acids, C16-18 and C18-unsatd., hexaesters with dipentaerythritolis expected to be low based on the molecular weight, size and structural complexity of the substance. These large and complex structures assume a high degree of conformational flexibility. Dimitrov et al. (2002) revealed a tendency of decreasing log BCF with an increase in conformational flexibility of molecules. They suggest that this effect is related to the enhancement of the entropy factor on membrane permeability of chemicals. This concludes a high probability that the substance may encounter the membrane in a conformation which does not enable the substance to permeate. Furthermore, the main components of the UVCB substance have high molecular weights of 1684 to 1853 g/mol. Thus, it is unlikely that they are readily absorbed due to the steric hindrance of crossing biological membranes. According to the Guidance on information requirements and chemical safety assessment; Chapter R.11: PBT Assessment (ECHA, 2012) a molecular weight of > 700 in combination with a calculated log Kow of > 8 can be used as enough evidence to conclude that a substance is unlikely to bioaccumulate. Following the ‘rule of 5’ (Lipinski et al., 2001), developed to identify drug candidates with poor oral absorption based on criteria in partitioning (log Kow > 5), molecular weight (> 500 g/mole), the substance is considered to be poorly absorbed after oral uptake (also see Hsieh & Perkins, 1976).

Metabolism

Esters of fatty acids are hydrolysed to the corresponding alcohol and fatty acids by esterases (Fukami & Yokoi, 2012). Depending on the route of exposure, esterase-catalysed hydrolysis takes place at different places in the organism: after oral ingestion, esters of alcohols and fatty acids undergo enzymatic hydrolysis already in the gastro-intestinal fluids. However, it is not anticipated that enzymatic hydrolysis of the parent substance is taking place in the gastrointestinal tract due to the high molecular weight and the complex structure of the molecule. Additionally, the hydrolysis of esterified alcohol with more than 3 ester groups is assumed to be slow (Mattson & Volpenheim, 1972). In in vivo studies in rats, a decrease in absorption was observed with increasing esterification. For example, pentaerythritol tetraoleate ester had an absorption rate of 64% and 90% (25% and 10% of dietary fat), whereas the hexaester of sorbitol was not absorbed (Mattson & Nolen, 1972). As Fatty acids, C16-18 and C18-unsatd., hexaesters with dipentaerythritol is a hexaester as well, the absorption rate is expected to be low. In contrast, substances which 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.
Fatty acids, C16-18 and C18-unsatd., hexaesters with dipentaerythritol are slowly hydrolysed to the corresponding alcohol (dipentaerythritol) and fatty acids by esterases. It was shown in-vitro that the hydrolysis rate for another polyol ester (pentaerythritol tetraoleate) was lower when compared with the hydrolysis rate of the triglyceride glycerol trioleate (Mattson & Volpenhein, 1972). Thus it is assumed that the hydrolysis rate for Fatty acids, C16-18 and C18-unsatd., hexaesters with dipentaerythritol is ever lower in comparison with pentaerythritol esters.
Therefore, ester bond hydrolysis is expected to occur to a minor extent in the gastrointestinal tract. Nevertheless possible cleavage products should be discussed here.
The first cleavage products, fatty acids 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 the citric acid cycle. For the complete catabolism of unsaturated fatty acids such as oleic acid, an additional isomerization reaction step is required. 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 dipentaerythritol can either remain unchanged or may further be metabolized or conjugated (e.g. glucuronides, sulfates, etc.) to polar products that are excreted in the urine.
Overall, the part ofFatty acids, C16-18 and C18-unsatd., hexaesters with dipentaerythritolthat have become systemically available, might be hydrolysed and the cleavage products can be further metabolized. However, due to its high molecular weight, absorption ofFatty acids, C16-18 and C18-unsatd., hexaesters with dipentaerythritolis not likely and thus, no extensive metabolism is expected but rather direct elimination.

Data from QSAR calculation

The interaction between lipophilicity, bioavailability and membrane permeability is considered to be the main reasons why the relationship between the bioaccumulation potential of a substance and its hydrophobicity is commonly found to be described by a relatively steep Gaussian curve with the bioaccumulation peak approximately at log Kow of 6-7 (e.g., see Dimitrov et al., 2002; Nendza & Müller, 2007; Arno and Gobas 2003). Substances with log Kow values above 10, which have been calculated for the major components of the UVCB substance, are considered to have a low bioaccumulation potential (e.g., Nendza & Müller, 2007; 2010). Furthermore, for those substances with a log Kow value > 10 it is unlikely that they reach the pass level of being bioaccumulative according to OECD criteria for the PBT assessment (BCF > 2000; ECHA, 2012). This assumption is supported by QSAR calculations using BCFBAF v3.01.BCF/BAF values calculated for the single components of the substance exhibit a low bioaccumulation potential (Blum, 2011). A calculated BCF/BAF of 0.89 L/kg (SRC BCFBAF v3.01 Arnot Gobas, upper trophic level) indicates that the substance has a low bioaccumulation potential.Even though the main components of the substance are outside the applicability domain of the model it might be used as supporting indication that the potential of bioaccumulation is low. The model training set is only consisting of substances with log Kow values of 0.31 - 8.70. But it supports the tendency that substances with high log Kow values (> 10) have a lower potential for bioconcentration as summarized in the ECHA Guidance R.11 (ECHA, 2012) and they are not expected to meet the B/vB criterion, which is also in accordance with Annex IX of Regulation (EC) No 1907/2006.

Conclusion

The bioaccumulation potential of Fatty acids, C16-18 and C18-unsatd., hexaesters with dipentaerythritol (CAS 68604-38-6) is expected to be low. The substance is characterised by a low water solubility and high log Koc leading to a low bioavailability. Due to its high molecular weight, no extensive metabolism of the substance is expected but rather direct elimination. In conclusion, a bioaccumulation or biomagnification through the food chain of the substance is not expected.
It can hence be concluded that the high log Kow, which indicates a potential for bioaccumulation, overestimates the bioaccumulation potential of the substance.

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