Fatty acids, C8-10, mixed esters with neopentyl glycol and trimethylolpropane

Bioaccumulation: aquatic / sediment

Description of key information

The potential for bioaccumulation of Fatty acids, C8-10 (even numbered), diesters with neopentyl glycol and di- and triesters with trimethylolpropane is assumed to be low based on all available data.

Additional information

Experimental bioaccumulation data are not available for Fatty acids, C8-10 (even numbered), diesters with neopentyl glycol and di- and triesters with trimethylolpropane. The high log Kow of 7.66-13.59 as an intrinsic chemical property of the substance 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 give a reliable assessment on bioaccumulation. In conclusion the substance is likely to show negligible bioaccumulation potential.

Environmental behavior

Due to ready biodegradability and high potential of adsorption, the substance can be effectively removed in conventional sewage treatment plants (STPs) by biodegradation and by sorption to biomass. The low water solubility (< 0.15 mg/L at 20 °C) and high estimated log Koc indicate that the substance is highly lipophilic. If released into the aquatic environment, the substance undergoes extensive biodegradation and sorption on organic matter. Thus, the bioavailability in the water column is reduced rapidly. The relevant route of uptake of Fatty acids, C8-10 (even numbered), diesters with neopentyl glycol and di- and triesters with trimethylolpropane by aquatic organisms is expected to be predominantly by ingestion of particle bound substance. 

Metabolism of aliphatic esters

The smaller the molecule, the more easily it will be taken up. In general, molecular weights below 500 are favourable for oral absorption (ECHA, 2014). With a molecular weight range of 356.54 - 596.94, absorption of Fatty acids, C8-10 (even numbered), diesters with neopentyl glycol and di- and triesters with trimethylolpropane (CAS 97281-24-8) is in general expected to be low in the gastrointestinal (GI) tract. The predicted log Pow >4 suggests that Fatty acids, C8-10 (even numbered), diesters with neopentyl glycol and di- and triesters with trimethylolpropane (CAS 97281-24-8) may be absorbed by micellar solubilisation, as this mechanism is of importance for highly lipophilic substances that are poorly soluble in water (1 mg/L or less). Applying the “Lipinski Rule of Five” (Lipinski et al. (2001), refined by Ghose et al. (1999)) to Fatty acids, C8-10 (even numbered), diesters with neopentyl glycol and di- and triesters with trimethylolpropane (CAS 97281-24-8), shows that two rules are not fulfilled: the substance has a molecular weight range above 500 and has more than 10 hydrogen bonds. This indicates a moderate to low potential for oral absorption. Please refer to the toxicokinetic statement in IUCLID section 7.1 for further information.

However, should the substance be taken up by fish during the process of digestion and absorption in the intestinal tissue, aliphatic esters like Fatty acids, C8-10 (even numbered), diesters with neopentyl glycol and di- and triesters with trimethylolpropane are expected to be initially metabolized via enzymatic hydrolysis to the corresponding free fatty acid (here: C8-C10) and the free fatty alcohols (here: trimethylolpropane and neopentylglycol). 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 reliable 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, 1980). The metabolism of the enzymatic hydrolysis products is presented in the following chapter.

Metabolism of enzymatic hydrolysis products

Fatty alcohols

Trimethylolpropane and neopentylglycol are the products from the enzymatic reaction of Fatty acids, C8-10 (even numbered), diesters with neopentyl glycol and di- and triesters with trimethylolpropane (CAS 97281-24-8) catalyzed by carboxylesterases. Both substances are expected to have a low potential for bioaccumulation (log Kow < 3).

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 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).

Data from QSAR calculation

Additional information on bioaccumulation could be gathered through BCF/BAF calculations using BCFBAF v3.01. The estimated BCF values for Fatty acids, C8-10 (even numbered), diesters with neopentyl glycol and di- and triesters with trimethylolpropane indicate negligible bioaccumulation in organisms. When including biotransformation, BCF/BAF values of 0.91 - 12.55/0.91 - 13.75 L/kg ww (Arnot-Gobas estimate, including biotransformation, upper trophic). Even though three out of four components of the UVCB substance are outside the applicability domain of the model, the (Q)SAR calculations 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 (> 10) 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, 2012).

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 Fatty acids, C8-10 (even numbered), diesters with neopentyl glycol and di- and triesters with trimethylolpropane 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 substance will not be bioaccumulative (all well below 2000 L/kg). The cleavage product neopentylglycol and trimethylolpropane have a low potential for bioaccumulation based on the low log Kow (< 3) and fatty acids are metabolised by common physiological processes.
Taking all these information into account, it can be concluded that the bioaccumulation potential of Fatty acids, C8-10 (even numbered), diesters with neopentyl glycol and di- and triesters with trimethylolpropane is low.