Fatty acids, tall-oil, esters with dipentaerythritol

Bioaccumulation: aquatic / sediment

Description of key information

Fatty acids, tall oil, esters with dipentaerythritol (CAS 70913-98-3) is expected to have a low potential for bioaccumulation.

Additional information

Tests on bioaccumulation of Fatty acids, tall oil, esters with dipentaerythritol (CAS 70913-98-3) are 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 correlates with the physico-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. Based on the high calculated partition coefficient (log Kow of main components: 42.27 - 48.16, KOWWIN v1.68; Kuckuck, 2013) bioaccumulation would be expected. However, this intrinsic property does not reflect the environmental fate of the substance. The calculated log Koc values of the main components of > 5 implies that the substance will adsorb to dissolved organic matter, suspended organic particles 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. Sediment-dwelling or benthic organisms may take the substance up by ingestion of contaminated sediment. Although the substance is not readily biodegradable elimination in sewage treatment plants is expected due to the very low water solubility and the high adsorption potential to sewage sludge. According to the Guidance on information requirements and chemical safety assessment, Chapter R7.b (ECHA, 2012) insoluble substances are largely removed in the primary settling tank and fat trap during the clarification and sedimentation process of waste water treatment. Only small amounts of the substance may enter the secondary treatment and thus get in contact with activated sludge. In conclusion, 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. A significant uptake of the substance by aquatic organisms through the water phase is therefore not expected. Taking all this into account, it can be assumed 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 of Fatty acids, tall oil, esters with dipentaerythritol (CAS 70913-98-3) is expected to be low based on the molecular weight, size and structural complexity of the substance. These large and complex structures presume a high degree of conformational flexibility. Dimitrov et al. (2002) described a tendency of decreasing log BCF with an increase in conformational flexibility of molecules. They indicate that this effect is related to the enhancement of the entropy factor on membrane permeability of chemicals. It was concluded with a high probability that the substance may encounter the membrane in a conformation which does not enable the substance to permeate. In addition, the main components of the UVCB substance have high molecular weights of 1684 to 1853 g/mol. It is therefore 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. According to 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), Fatty acids, tall oil, esters with dipentaerythritol (CAS 70913-98-3) 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-vivo studies in ratsshowed a decrease in absorption 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, tall oil, esters with dipentaerythritol (CAS 70913-98-3) 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, tall oil, esters with dipentaerythritol (CAS 70913-98-3) is 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). It is therefore assumed that the hydrolysis rate for Fatty acids, tall oil, esters with dipentaerythritol (CAS 70913-98-3) is ever lower in comparison with pentaerythritol esters. In conclusion, ester bond hydrolysis is expected to occur to a minor extent in the gastrointestinal tract. However, 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. In summary, the part of Fatty acids, tall oil, esters with dipentaerythritol (CAS 70913-98-3) that have become systemically available, might be hydrolysed and the cleavage products can be further metabolized. Nevertheless, due to its high molecular weight, absorption of Fatty acids, tall oil, esters with dipentaerythritol (CAS 70913-98-3) is not likely and thus, no extensive metabolism is expected but rather direct elimination.

Data from QSAR calculation

The impact between bioavailability, lipophilicity and membrane permeability is considered to be the main reason 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; Arnot 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). Additionally, 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). QSAR calculations using BCFBAF v3.01 for the single components of the substance also exhibit a low bioaccumulation potential (Kuckuck, 2013). A calculated BCF/BAF of 0.89 L/kg (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 of a low bioaccumulation potential. 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, tall oil, esters with dipentaerythritol (CAS 70913-98-3) is expected to be low. The substance is characterised by a high log Koc and low water solubility 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 therefore 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 the CSR.