Dodecyl laurate

Bioaccumulation: aquatic / sediment

Description of key information

Based on the available data, the potential of bioaccumulation for lauryl laurate (CAS 13945-76-1)is expected to be low.

Additional information

The substance has a high, estimated log Kow of > 10.0 (Meylan/Kowwin v1.1.4 calculation), suggesting a high potential for bioaccumulation. Experimental data for bioaccumulation are not available. However, all the available information on the environmental behaviour and metabolism discussed below provide evidence that the effective potential for bioaccumulation is likely negligible.

Environmental behaviour

The very low water solubility (< 1 µg/L, 20 °C and pH 6.3, OECD 105) and high estimated log Kow (> 10.0, Meylan/Kowwin v1.1.4 calculation) indicate that the substance is highly lipophilic. However, only low concentrations pf the substance are expected to reach the environment in the first place, 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 sorption to biomass. Whatever fraction reaches the aquatic environment is expected to undergo extensive biodegradation and sorption to organic matter, leading to an effective reduction of bioavailability in the water column. 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 high sorption potential of the substance, the bioavailability in the sediment is presumably also very low, which reduces the probability of chronic exposure of sediment organisms in general.

Metabolization of aliphatic esters

The substance is an aliphatic ester. In the case where aliphatic esters should be ingested by fish, they 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. Hydrolysis is catalyzed by classes of enzymes known as carboxylesterases or esterases (Heymann, 1980). 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). Carboxylesterase activity has been noted in a wide variety of tissues in fish as well as in invertebrates (Leinweber, 1987; Soldano et al, 1992; Barron et al., 1999, Wheelock et al., 2008). In mammals, the most important are the B-esterases in the hepatocytes (Heymann, 1980; Anders, 1989).

Furthermore, it is known that esters 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 explained 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

The metabolism of alcohols is well known. 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 metabolism of alcohols 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 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 show a high degree of similarity in biotransformation compared to linear alcohols. They will be oxidized to the corresponding carboxylic acid followed by the ß-oxidation as well. The 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 (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 leading to a decreased elimination.

Fatty acids

The metabolization 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 constitute 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

The biochemical processes involved in the metabolization of aliphatic esters, comprising enzymatic hydrolysis and the subsequent metabolization of the corresponding carboxylic acid and alcohol, are ubiquitous in the animal kingdom. Hence, 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). This conclusion is supported by (Q)SAR calculations for BCF values in fish, with estimated BCF values of 52.6 L/kg wet-wt (regression-based estimate) and 1.403 L/kg wet-wt (Arnot-Gobas, including biotransformation, upper trophic) and as such, are well below the threshold value of 2000 L/kg for bioaccumulative substances, as laid down by the REACH regulation (EC) No 1907/2006, section 1 of Annex XIII.

Thus, in consideration of all the available information, it can be concluded that the potential for bioaccumulation of lauryl laurate (CAS 13945-76-1) is low.

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

REFERENCES

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