Hexanoic acid, 2-ethyl-, C16-18-alkyl esters

Bioaccumulation: aquatic / sediment

Description of key information

Hexanoic acid, 2-ethyl-, C16-18 alkyl esters (CAS No. 90411-68-0) exhibits a low potential for bioaccumulation, based on QSAR calculations and rapid metabolisation as expected for this substance.

Additional information

No experimental data evaluating the bioaccumulation potential of Hexanoic acid, 2-ethyl-, C16-18 alkyl esters (CAS No. 90411-68-0) is available. The substance exhibits a high log Kow (experimental log Kow = 5.82, calculated log Kow > 10), suggesting potential to bioaccumulate in biota. However, the information gathered on environmental behaviour and metabolism, in combination with QSAR-estimated values, provide enough evidence (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) to state that this substance is likely to show negligible bioaccumulation potential.

Intrinsic properties and fate

Hexanoic acid, 2-ethyl-, C16-18 alkyl esters is readily biodegradable. According to the Guidance on information requirements and chemical safety assessment, Chapter R.7b, readily biodegradable substances can be expected to undergo rapid and ultimate degradation in most environments, including biological Sewage Treatment Plants (STPs) (ECHA, 2012b). Therefore, after passing through conventional STPs, only low concentrations of these substances are likely to be (if at all) released into the environment.

Hexanoic acid, 2-ethyl-, C16-18 alkyl esters exhibits a high log Kow and a water solubility < 0.15 mg/L. The Guidance on information requirements and chemical safety assessment, Chapter R.7b (ECHA, 2012b) states that once insoluble chemicals enter a standard STP, they will be extensively removed in the primary settling tank and fat trap and thus, only limited amounts will get in contact with activated sludge organisms. Nevertheless, once this contact takes place, these substances are expected to be removed from the water column to a significant degree by adsorption to sewage sludge (Guidance on information requirements and chemical safety assessment, Chapter R.7a, ECHA, 2012a) and the rest will be extensively biodegraded (due to ready biodegradability). Thus, discharged concentrations of these substances into the aqueous compartment are likely to be very low. Should the substances be released into the water phase, due to their hydrophobicity and expected high adsorption potential, they will tend to bind to sediment and other particulate organic matter, and therefore, the actual dissolved fraction available to fish via water will be reduced. Thus, the main route of exposure for aquatic organisms such as fish will be via food ingestion or contact with suspended solids.

QSAR data

Additional information on the bioaccumulation of Hexanoic acid, 2-ethyl-, C16-18 alkyl esters in fish species is available. Estimated bioconcentration (BCF) and bioaccumulation (BAF) values were calculated for this substance using the BCFBAF v3.01 program (Estimation Programs Interface Suite™ for Microsoft® Windows v 4.10., US EPA), including biotransformation rates (Arnot-Gobas method). Even though the log Kow values of the main components are outside the applicability domain of the used model (model training set is constituted of substances with log Kow values in the range of 0.31 to 8.70), the calculations (especially the low BCF values calculated using the Arnot-Gobas method) reflect the rapid biotransformation assumed for Hexanoic acid, 2-ethyl-, C16-18 alkyl esters. The calculated BCF and BAF values are 19-57 L/kg (BCF, regression based estimate) and < 130 L/kg (Arnot-Gobas method, BCF and BAF, respectively). BCF calculations reflect the bioaccumulation potential after uptake via water, whereas the BAF gives an indication of the bioaccumulation when all exposure routes (water, food, etc.) are taken into account.

The obtained results indicate that Hexanoic acid, 2-ethyl-, C16-18 alkyl esters is likely to show negligible bioaccumulation potential. According to Regulation (EC) No. 1907/2006, Annex XIII, 1.1.2, a substance only fulfills the bioaccumulation criterion (B) when BCF values are > 2000. Even though this condition is preferred to be confirmed with experimental data, in this case the estimated QSAR-based BCFs provide sufficient reliable evidence which suggests that the substance will not be bioaccumulative.

Metabolism of Hexanoic acid, 2-ethyl-, C16-18 alkyl esters

If Hexanoic acid, 2-ethyl-, C16-18 alkyl esters is uptaken by living organisms, aliphatic esters such as the substance will be initially metabolized via enzymatic hydrolysis to the respective fatty acid and alcohol components as would other dietary fats (e.g., Linfield, 1984). The hydrolysis is catalyzed by carboxylesterases and esterases, with B-esterases located in hepatocytes of mammals being the most important (Heymann, 1980; Anders, 1989). However, carboxylesterase activity has also been reported from a wide variety of tissues in invertebrates and fishes (e.g., Leinweber, 1987; Suldano et al., 1992; Barron et al., 1999; Wheelock et al., 2008). In fish, the high catalytic activity, low substrate specificity and wide distribution of the enzymes in conjunction with a high tissue content lead to a rapid biotransformation of aliphatic esters, which significantly reduces its bioaccumulation potential (Lech & Melancon, 1980; Lech & Bend, 1980).

Metabolites

C16/C18 fatty alcohols and 2-ethylhexanoic acid are the expected hydrolysis products from the enzymatic reaction catalyzed by carboxylesterase. The metabolism of fatty alcohols has been intensively reviewed in the literature (e.g., see Rizzo et al., 1987; Hargrove et al., 2004). The free alcohols can either be esterified to form wax esters (which are similar to triglycerides) or they can be transformed to fatty acids in a two-step enzymatic process catalyzed by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). The responsible enzymes ADH and ALDH are present in a large number of animals including plants, microorganisms and fish (e.g., Sund & Theorell, 1963; Nilsson, 1990; Yoshida et al., 1997; Reimers et al., 2004; Lassen et al., 2005). 

The metabolism of alcohols in fish was intensively studied by Reimers et al. (2004). They isolated and characterized two cDNAs from the zebra fish, Danio rerio, encoding ADHs, which showed specific metabolic activity in in-vitro assays with various alcohol components ranging from C4 to C8. The emerging aldehydes were shown to be further oxidized to the corresponding fatty acid by ALDH enzymes. The most effective ALDH2, which is mainly located in the mitochondria of liver cells showed a similarity of 75% to mammalian ALDH2 enzymes and a similar catalytic activity (also see Nilsson, 1990). The same metabolic pathway was shown for longer chain alcohols, such as stearyl and oleyl alcohol in the intestines of rats (Sieber et al., 1974).

The further metabolism of the fatty acids is also well investigated in various organisms, such as plants (e.g., Harwood 1988), fish (e.g., Henderson, 1996; Turchini, 2006) or algae (e.g., Nichols, 1968). The free fatty acids can either be stored as triglycerides or be oxidized via mitochondrial ß-oxidation removing C2-units, in order to store usable energy in form of ATP (Masoro, 1977). Acetyl-CoA, the final product of the ß-oxidation process, can further be mineralized in the tricarboxylic acid cycle via different enzymatically catalyzed processes to carbon dioxide.

Conclusion

Hexanoic acid, 2-ethyl-, C16-18 alkyl esters is not expected to be bioaccumulative. Due to its readily biodegradable nature, extensive degradation of this substance in conventional STPs will take place and only low concentrations are expected to be released (if at all) into the environment. Once present in the aquatic compartment, further biodegradation will occur and, due the high log Kow will be bioavailable to aquatic organisms such as fish mainly via feed and contact with suspended organic particles. After uptake by fish species, extensive and fast biotransformation of the substance into C16/C18 fatty alcohols and 2-ethylhexanoic acid is expected. The supporting BCF/BAF values estimated with the BCFBAF v3.01 program also indicate that this substance will not be bioaccumulative (all well below 2000 L/kg).

The information above provides strong evidence supporting the statement that rapid metabolism and low bioaccumulation potential can be expected for this substance.

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