2-octyldodecyl 12-[(1-oxooctadecyl)oxy]octadecanoate

Bioaccumulation: aquatic / sediment

Description of key information

Based on all the available data, the potential for bioaccumulation of 2-octyldodecyl 12-[(1-oxooctadecyl)oxy]octadecanoate (CAS 90052-75-8) is expected to be low.

 

Additional information

The substance has a high, estimated log Kow of > 10 (QSAR, EPI Suite v4.11, KOWWIN v1.68), suggesting a high potential for bioaccumulation. Experimental data for bioaccumulation are not available. However, all the available information on environmental behavior and metabolism, in combination with QSAR calculations, provide sound evidence suggesting that the effective potential for bioaccumulation is negligible.

 

Environmental behavior

The low water solubility (< 0.05 mg/L, 20 °C) and high estimated log Kow (> 10, KOWWIN v1.68) indicate that the substance is highly lipophilic. If released into the aquatic environment, the substance is expected to undergo extensive biodegradation and sorption to organic matter leading to an effective reduction of its bioavailability in the water column. However, only low concentrations of the substance are expected to be released into the environment (if at all). Due to the ready biodegradability and high potential for adsorption, the substance is effectively removed from conventional sewage treatment plants (STPs) by biodegradation and by sorption to biomass. Thus, the overall bioavailability of the substance in surface water is presumably low and the most relevant route of uptake by aquatic organisms is expected to occur via ingestion of particle bound substance.

However, based on the intrinsic physico-chemical properties of the substances, its bioavailability in the sediment environment is presumably very low, which reduces the probability of chronic exposure of sediment organisms in general.

Metabolization of aliphatic esters

Should the substance be taken up by fish, aliphatic esters are expected to be initially metabolized via enzymatic hydrolysis during the process of digestion and absorption in the intestinal tissue, resulting in the corresponding free fatty acids and the free fatty alcohols. 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/metabolization of xenobiotics, which reduces the bioaccumulation or bioconcentration potential (Lech & Bend, 1980). It is known for esters that they are readily metabolized in fish (Barron et al., 1999) and literature clearly shows 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 metabolization of the enzymatic hydrolysis products is presented in the next section below.

Metabolization 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 of the enzymatic reaction of long chain aliphatic esters catalyzed by carboxylesterases. The metabolization 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 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 organism 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 their corresponding acids 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 which lead to a decreased elimination.

Fatty acids

The metabolism of fatty acids in mammals is well known and has been investigated intensively (Stryer, 1994). 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 triglycerides in fat tissue and re-mobilized for energy production, it 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).

Conclusion

Based on the enzymatic hydrolysis of aliphatic esters and the subsequent metabolization 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 substance since it does not take into account the metabolization of substances in living organisms. Current knowledge suggests that log Kow values of 10 or above are indicators of reduced bioconcentration, as stated in the Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.7c: Endpoint specific guidance (ECHA, 2017) as well as in Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.11: PBT/vPvB assessment v2.0 (ECHA, 2017). Furthermore, the biochemical processes for the metabolization of aliphatic esters is ubiquitous in the animal kingdom.

In consideration of all the available information, it can be concluded that the potential for bioaccumulation of 2-octyldodecyl 12-[(1-oxooctadecyl)oxy]octadecanoate (CAS 90052-75-8) is low.

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