Dodecyl oleate

Bioaccumulation: aquatic / sediment

Description of key information

The potential for bioaccumulation of the LCAE category members is low based on all available data.

Additional information

Aquatic bioaccumulation of Long Chain Aliphatic Esters

Experimental bioaccumulation data are not available for the members of the Long Chain Aliphatic Esters (LCAE) category. The high log Kow (> 7) as an intrinsic chemical property of the category members indicates a potential for bioaccumulation. However, the information gathered on environmental behaviour and metabolism, in combination with QSAR-estimated values, provide enough evidence (in accordance to the 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 these substances are likely to show negligible bioaccumulation potential.

Environmental behavior

Due to ready biodegradability and high potential of adsorption, the category members can be effectively removed in conventional sewage treatment plants (STPs) by biodegradation and by sorption to biomass. The low water solubility (< 0.05 mg/L) and high estimated log Kow values indicate that the members of the LCAE category are highly lipophilic. If released into the aquatic environment, the category members undergo extensive biodegradation and sorption on organic matter. Thus, the bioavailability of these substances in the water column is reduced rapidly. The relevant route of uptake of LCAE in aquatic organisms is considered predominatly by ingestion of particle bound substance. 

Metabolism of aliphatic esters

Should category members be taken up by fish during the process of digestion and absorption in the intestinal tissue, aliphatic esters like LCAE are expected to be initially metabolized via enzymatic hydrolysis to the corresponding free fatty acids and the free fatty alcohols such as oleic acid and tetradecan-1-ol, for example. The hydrolysis is catalyzed by classes of enzymes known as carboxylesterases or esterases (Heymann, 1980). The most important of which are the B-esterases in the hepatocytes of mammals (Heymann, 1980; Anders, 1989). 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, E., 1980). The metabolism of the enzymatic hydrolysis products is presented in the following chapter.

Metabolism of enzymatic hydrolysis products

Fatty alcohols

Fatty alcohols ranging from C8 (octan-1-ol) to C22 (docosan-1-ol), including unsaturated and branched alcohols, are the products from the enzymatic reaction of the LCAE catalyzed by carboxylesterases. The metabolism of alcohols is well known. The free alcohols can either be esterified to form wax esters which are similar to triglycerides or they can be metabolized to fatty acids in a two-step enzymatic process by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) using NAD+ as coenzyme as shown in the fish gourami (Trichogaster cosby) (Sand et al., 1973). The responsible enzymes ADH and ALDH are present in a large number of animals, plants and microorganisms (Sund & Theorell, 1963; Yoshida et al., 1997). They were found among others in the zebrafish (Reimers et al., 2004; Lassen et al., 2005), carp and rainbow trout (Nilsson, 1988; Nilsson, 1990).

 

The alcohol metabolism was also investigated in the zebrafish Danio rerio, which is a standard organisms in aquatic ecotoxicology. Two cDNAs encoding zebrafish ADHs were isolated and characterized. A specific metabolic activity was shown in in-vitro assays with various alcohol components ranging from C4 to C8. The corresponding aldehyde can be further oxidized to the fatty acid catalyzed by an ALDH. Among the ALDHs the ALDH2, located in the mitochondria is the most efficient. The ALDH2 cDNA of the zebrafish was cloned and a similarity of 75% to mammalian ALDH2 enzymes was found. Moreover, ALDH2 from zebra fish exhibits a similar catalytic activity for the oxidation of acetaldehyde to acetic acid compared to the human ALDH2 protein (Reimers at al., 2004). The same metabolic pathway was shown for longer chain alcohols like stearyl- and oleyl alcohol which were enzymatically converted to its corresponding acid, in the intestines (Calbert et al., 1951; Sand et al., 1973; Sieber, et al., 1974). Branched alcohols like 2-hexyldecanol or 2-octyldodecanol show a high degree of similarity in biotransformation compared to the linear alcohols. They will be oxidized to the corresponding carboxylic acid followed by the ß-oxidation as well. A presence of a side chain does not terminate the ß-oxidation process (OECD, 2006).

The influence of biotransformation on bioaccumulation of alcohols was confirmed in GLP studies with the rainbow trout (according to OECD 305) with commercial branched alcohols with chain lengths of C10, C12 and C13 as reported in de Wolf & Parkerton, 1999. This study resulted in an experimental BCF of 16, 29 and 30, respectively for the three alcohols tested. The 2-fold increase of BCF for C12 and C13 alcohol was explained with a possible saturation of the enzyme system and thus leading to a decreased elimination.

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 calculation

Additional information on bioaccumulation could be gathered through BCF/BAF calculations using BCFBAF v3.01. The estimated BCF values for the LCAE indicate negligible bioaccumulation in organisms (BCF: 42.84 L/kg, regression based). When including biotransformation, BCF and BAF values of0.89 - 14.07 and 0.90 - 314 L/kg, respectively were obtained (Arnot-Gobas estimate, including biotransformation, upper trophic). Even though the members of the LCAE category are outside the applicability domain of the model they can 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 (> 7) 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, 2008).

Conclusion

The biochemical process metabolizing aliphatic esters is ubiquitous in the animal kingdom. Based on the enzymatic hydrolysis of aliphatic esters and the subsequent metabolism of the corresponding carboxylic acid and alcohol, it can be concluded that the high log Kow, which indicates a potential for bioaccumulation, overestimates the true bioaccumulation potential of the LCAE category members since it does not reflect the metabolism of substances in living organisms. BCF/BAF values estimated with the BCFBAF v3.01 program also indicate that the members of the LCAE category will not be bioaccumulative (all well below 2000 L/kg). Taking all these information into account, it can be concluded that the bioaccumulation potential of the LCAE category members is low.

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