Fatty acids, tall-oil, esters with trimethylolpropane

Bioaccumulation: aquatic / sediment

Additional information

Experimental data on bioaccumulation of fatty acids, tall-oil, triesters with trimethylolpropane (CAS 94581-09-6) 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 1907/2006 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)).

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: 7.69 - 24.73, KOWWIN v1.68; Müller, 2014) bioaccumulation would be expected. However, this intrinsic property does not reflect the environmental fate of the substance.

Environmental fate

Due to the ready biodegradability and the high adsorption potential an effective removal of fatty acids, tall-oil, triesters with trimethylolpropane in sewage treatment plants is expected. However, when released to the aquatic environment a rapid degradation is anticipated.The calculated log Koc values of the main components of > 3 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.

 

Metabolism of enzymatic hydrolysis products

On the basis of the properties of the test substance characteristics a low absorption of Fatty acids, tall-oil, triesters with trimethylolpropane is predicted.

Metabolism of aliphatic esters

The hydrolysis of esterified alcohol with more than three ester groups is assumed to be slow. This is supported by in-vivo studies in rats, in which a decrease in absorption was observed with increasing esterification. For example, for the polyol ester Pentaerythritol tetraoleate an absorption rate of 64% and 90% (25% and 10% of dietary fat) was observed while an absorption rate of 100% was observed for glycerol trioleate when ingested at 100%of dietary fat (Mattson and Nolen, 1972).In addition it has been shown in-vitro that the hydrolysis rate of another polyol ester (pentaerythritol tetraoleate) was lower when compared with the hydrolysis rate of the triglyceride glycerol trioleate (Mattson and Volpenhein, 1972a).

Esters of fatty acids are hydrolysed to the corresponding alcohol and fatty acid by esterases (Fukami and 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. 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.

Carboxylesterase activity has been noted in a wide variety of tissues in invertebrates as well as in fish (Leinweber, 1987; Soldano et al, 1992; Barron et al., 1999, Wheelock et al., 2008). The catalytic activity of this enzyme family leads to a rapid biotransformation/metabolism of xenobiotics which reduces the bioaccumulation or bioconcentration potential (Lech & Bend, 1980). It is known for esters that they are readily susceptible to metabolism in fish (Barron et al., 1999) and literature data have clearly shown that esters do not readily bioaccumulate in fish (Rodger & Stalling, 1972; Murphy & Lutenske, 1990; Barron et al., 1990). In fish species, this might be caused by the wide distribution of carboxylesterase, high tissue content, rapid substrate turnover and limited substrate specificity (Lech & Melancon, 1980; Heymann, 1980). The metabolism of the enzymatic hydrolysis products is presented in the following.

Metabolism of trimethylolpropane

Due to its physico-chemical properties (low molecular weight, low logKow, and solubility in water), trimethylolproaneis easily absorbed and 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 (OECD SIDS, 2013). Moreover, trimethylolpropane showed a very low bioaccumulation potential in a GLP OECD 305C study (BCF: < 1) and is of low toxicity to aquatic organisms (OECD, 1994).

Metabolism of fatty acids

The metabolism of fatty acids in mammals is well known and has been investigated intensively in the past (Stryer, 1994). The free fatty acids can either be stored as triglycerides or oxidized via mitochondrial ß-oxidation removing C2-units to provide energy in the form of ATP (Masoro, 1977). Acetyl-CoA, the product of the ß-oxidation, can further be oxidized in the tricarboxylic acid cycle to produce energy in the form of ATP. As fatty acids are naturally stored as trigylcerides in fat tissue and re-mobilized for energy production is can be concluded that even if they bioaccumulate, bioaccumulation will not pose a risk to living organisms. Fatty acids (typically C14 to C24 chain lengths) are also a major component of biological membranes as part of the phospholipid bilayer and therefore part of an essential biological component for the integrity of cells in every living organism (Stryer, 1994). Saturated fatty acids (SFA; C12 - C24) as well as mono-unsaturated (MUFA; C14 - C24) and poly-unsaturated fatty acids (PUFA; C18 - C22) were naturally found in muscle tissue of the rainbow trout (Danabas, 2011) and in the liver (SFA: C14 - C20; MUFA: C16 - C20; PUFA: C18 - C22) of the rainbow trout (Dernekbasi, 2012).

Data from QSAR calculations

Calculated BCF/BAF values indicate a low bioaccumulation potential of fatty acids, tall-oil, triesters with trimethylolpropane (BCFBAF v3.01; Müller, 2014). Calculations including the normalized whole-body metabolic biotransformation rate constant gave a BCF of 0.89 - 18.94 and a BAF of 0.89 - 30 L/kg (Arnot-Gobas, upper trophic). Even though the di- and the triester components of the substance are outside the applicability domain of the model (Training set: substance with log Kow values of 0.31 - 8.70) it was used as supporting indication that the potential of bioaccumulation is low and 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 and they are not expected to meet the B/vB criterion (ECHA, 2012). However, the monoester component of the substance was within the applicability domain of the model resulting in reliable low BCF/BAF-values (BCF: 18.94 L/kg; BAF: 30 L/kg) indicating a low potential for bioaccumulation.

Conclusion
The bioaccumulation potential of the test substance is expected to be low. The substance is characterized by a rapid degradation and low water solubility causing a low bioavailability. If taken up the substance is biotransformed to fatty acids and the corresponding alcohol component by the ubiquitous carboxylesterase enzymes in aquatic species. Based on the rapid metabolism it can be concluded that the high log Kow, which indicates a potential for bioaccumulation, overestimates the bioaccumulation potential of fatty acids, tall-oil, triesters with trimethylolpropane.

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