Fatty acids C18-C22 (even numbered), tetraesters with pentaerythritol

Bioaccumulation: aquatic / sediment

Description of key information

The potential for bioaccumulation of fatty acids C18-C22 (even numbered), tetraesters with pentaerythritol is assumed to be low based on available data.

Additional information

Experimental data on bioaccumulation of fatty acids C18-C22 (even numbered), tetraesters with pentaerythritol is not available. The evaluation of the bioaccumulation potential of the substance is therefore based on a Weight of Evidence (WoE), combining all available related data. This is in accordance to the REACh 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. 1907/2007 Annex IX and X (Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance (ECHA, 2017). 

Environmental behaviour

Due to the high potential for adsorption, the substance can be effectively removed in conventional sewage treatment plants (STPs) by sorption to biomass. The low water solubility (< 0.518 mg/L at 20 °C, OECD 105) and high estimated log Kow (> 10, QSAR, VEGA 1.1.3) indicate that the substance is highly lipophilic. If released into the aquatic environment, the substance undergoes extensive sorption to organic matter. Thus, the bioavailability in the water column is highly reduced. The relevant route of uptake of the substance in aquatic organisms is expected to be predominantly by ingestion of particle bound substance. 

Uptake/Absorption

If the substance is taken up by ingestion, absorption is expected to be low based on the molecular weight, size and structural complexity of the substance. Large and complex structures like fatty acids C18-C22 (even numbered), tetraesters with pentaerythritol assume a high degree of conformational flexibility. Dimitrov et al. (2002) revealed a tendency of decreasing log BCF with an increase in conformational flexibility of molecules. They suggest that this effect is related to the enhancement of the entropy factor on membrane permeability of chemicals. This concludes a high probability that the substance may encounter the membrane in a conformation which does not enable the substance to permeate. Furthermore, the substance has a high molecular weight of 1370.31 – 1426.42 g/mol. Thus, it is unlikely that it is readily absorbed, due to the steric hindrance of crossing biological membranes. Following the ‘rule of 5’ (Lipinski et al., 2001), developed to identify drug candidates with poor oral absorption based on criteria regarding partitioning (log Kow > 5) and molecular weight (> 500 g/mol), the substance is considered to be poorly absorbed after oral uptake (Hsieh & Perkins, 1976).

This interaction between lipophilicity, bioavailability and membrane permeability is considered to be the main reasons why the relationship between the bioaccumulation potential of a substance and its hydrophobicity is commonly described by a relatively steep Gaussian curve with the bioaccumulation peak approximately at log Kow of 6-7 (e.g., see Dimitrov et al., 2002; Nendza & Müller, 2007; Arnot and Gobas 2003). Substances with log Kow values above 10, which has been calculated for the test substance, are considered to have a low bioaccumulation potential (e.g. Nendza & Müller, 2007; 2010). Furthermore, for those substances with a log Kow value > 10 it is unlikely that they reach the pass level of being bioaccumulative according to OECD criteria for the PBT assessment (BCF > 2000; ECHA, 2017). In addition, in a 90-day oral feeding toxicity study with an analogue substance no treatment-related and no toxicologically relevant effects for mammals were observed in the study.

This assumption is supported by QSAR calculations using BCFBAF v3.01 performed for the main components of fatty acids C18-C22 (even numbered), tetraesters with pentaerythritol. BCF/BAF values of 3.16 L/kg (regression based) and 0.89 L/kg (Arnot-Gobas estimate, including biotransformation, upper trophic) were obtained, respectively. Even though fatty acids C18-C22 (even numbered), tetraesters with pentaerythritol is outside the applicability domain of the model, the estimation can be used as supporting indication of low bioaccumulation potential. The model training set is only consisting of substances with log Kow values of -1.37 – 11.26 (regression based) and 0.31 - 8.70 (Arnot-Gobas). But it supports the tendency that substances with high log Kow values (> 10) have a lower potential for bioconcentration and accumulation as summarized in the ECHA Guidance R.11 and they are not expected to meet the B/vB criterion (ECHA, 2017).

Conclusion

Based on the physico/chemical properties such as low water solubility and high potential for adsorption a reduced availability in water is expected. The high molecular weight of the substance significantly reduces the absorption due to sterical hindrance to cross biological membranes. In addition, no toxicologically relevant effects in mammals were observed in a 90-day oral feeding toxicity study. It can be concluded that the bioaccumulation potential of fatty acids C18-C22 (even numbered), tetraesters with pentaerythritol is negligible. BCF/BAF values estimated by QSAR (BCFBAF v3.01) also support this assumption (BCF values all well below 2000 L/kg).

Taking all these information into account, it can be concluded that bioaccumulation of fatty acids C18-C22 (even numbered), tetraesters with pentaerythritol is unlikely to occur.

References

Dimitrov et al. (2002): Predicting bioconcentration factors of highly hydrophobic chemicals. Effects of molecular size. Pure Appl. Chem., Vol. 74(10). 1823-1830

ECHA (2017): Guidance on information requirements and chemical safety assessment. Chapter R.11: PBT Assessment. European Chemicals Agency, Helsinki.

Hsieh, A. and Perkins, E. G. (1976). Nutrition and Metabolic Studies of Methyl Ester of Dimer Fatty Acids in the Rat. Lipids, 11(10):763-768.

Lipinski et al. (2001). Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Del. Rev. 46: 3-26.

Nendza, M. & Müller, M. (2010). Screening for low bioaccumulation (1): Lipinski's 'Rule of 5' and molecular size. SAR and QSAR in Environmental Research, 21(5-6), 495-512. Report date: 2010-04-26.

Nendza, M. and Müller, M. (2007).Literature Study: Effects of Molecular Size and Lipid Solubility on Bioaccumulation Potential. Testing laboratory: Fraunhofer Institute for Molecular Biology and Applied Ecology, Schmallenberg, Germany and Analytisches Laboratorium für Umweltuntersuchungen und Auftragsforschung, Luhnstedt, Germany. Report no.: FKZ 360 01 043. Owner company: Umweltbundesamt, Dessau, Germany. Report date: 2007-02-15.