Propanoic acid, 2-hydroxy-, C12-13-branched alkyl esters

Bioaccumulation: aquatic / sediment

Description of key information

The potential for bioaccumulation is assumed to be low (BCF: 45.78 - 61.6 L/kg (BCFBAF v3.01)).

Additional information

No experimental studies investigating the bioaccumulation potential of Propanoic acid, 2-hydroxy-, C12-13-branched-alkyl esters are available. Therefore, the bioaccumulation factor (BCF) of all components of the UVCB substance was estimated using a reliable QSAR model (BCFBAF v3.01; Müller, 2011). All components were in the applicability domain of the model indicating that the results are reliable and can be used to assess the bioaccumulation potential of Propanoic acid, 2-hydroxy-, C12-13-branched-alkyl esters. The BCF was calculated to be in the range of 45.78 - 61.6 L/kg (upper trophic) using the model of Arnot-Gobas which includes biotransformation. Exclusion of biotransformation resulted in clearly higher BCF values of 4808 - 11080 L/kg. Thus, it can be concluded that the substance will be extensively metabolized (bio half-life (normalized to 10 g fish at 15 °C) of 0.11 - 0.15 d) which reduces the bioaccumulation potential significantly.The result from the BCF regression model is in line with the BCF/BAF Arnot-Gobas model resulting in BCF values of 25.8 - 54.5 L/kg.

In general, alkyl esters are readily hydrolysed in the gastrointestinal tract, blood and liver to the corresponding alcohol and fatty acid by the enzymatic activity of ubiquitous carboxylesterases. The substance Propanoic acid, 2-hydroxy-, C12-13-branched-alkyl esters is therefore anticipated to be hydrolysed to lactic acid and branched alcohols with C12 and C13 chain length, respectively (see IUCLID Section 7.1). Lactic acid occurs endogenously as a component of various physiological pathways, and is thus anticipated to be readily absorbed and metabolised (Lehninger, 1993). 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.

In conclusion, due to the low estimated BCF values including biotransfomation,Propanoic acid, 2-hydroxy-, C12-13-branched-alkyl estershas a low potential for bioaccumulation. Calculated BCF values are clearly below the trigger value of 2000 L/kg to be classified as bioaccumulative (B-criterion; ECHA Guidance R.11, 2012). This assumption is supported by available data on metabolism of the substance.