Isononanoic acid, mixed esters with dipentaerythritol, heptanoic acid and pentaerythritol

Bioaccumulation: aquatic / sediment

Description of key information

If aquatic exposure occurs, 3,5,5 trimethylhexanoic acid, mixed esters with dipentaerythritol (CAS 84418-63-3) will be mainly taken up by ingestion but absorption is expected to be low based on the molecular weight, size and structural complexity of the substance. The substance is thus not expected to bioaccumulate in aquatic or sediment organisms and secondary poisoning does not pose a risk.

Additional information

Experimental data for bioaccumulation in water are not available for 3,5,5 trimethylhexanoic acid, mixed esters with dipentaerythritol (CAS 84418-63-3). In principle, the estimated high log Kow value of > 10 (KOWWIN v1.68) indicates a potential for bioaccumulation. Nevertheless, this intrinsic property of the substance does not reflect the environmental behaviour of the test substance or its absorption in living organisms. However, the information gathered on the absorption of the substance by aquatic organisms and environmental behavior, in combination with QSAR-estimated values provide enough evidence (in accordance to Regulation (EC) No 1907/2006, Annex XI, 1.2 General rules for adaptation of the standard testing regime set out in Annexed VII - X), to cover the data requirements of Regulation (EC) No 1907/2006, Annex VIII concluding that the substance is likely to show negligible bioaccumulation potential in aquatic organisms.

Environmental behaviour

3,5,5 trimethylhexanoic acid, mixed esters with dipentaerythritol is characterized by a high partition coefficient (calculated log Kow > 10, KOWWIN v1.68) indicating that the substance is highly lipophilic. The calculated log Koc value of > 5 indicate that the substance will adsorb to suspended organic particles, dissolved organic matter (DOM) and to some degree biota in the aquatic environment (e.g. see Jaffé, 1991). Considering the high degree of conformational flexibility, Dimitrov et al. (2002) revealed a tendency of decreasing log BCF with an increase in log Koc, the main uptake route is considered to be by ingestion of particle bounded substance via food. But it is expected that the substance will be effectively removed in conventional sewage treatment plants (STP) by sorption to biomass before entering the aquatic environment. Considering this, one can assume that the availability of the substance in the aquatic environment is generally low, which reduces the probability of uptake by aquatic organisms (e.g., see McKim et al, 1984; Björk, 1995; Haitzer et al., 1998). If the substance is taken up by ingestion, absorption of 3,5,5 trimethylhexanoic acid, mixed esters with dipentaerythritol is expected to be low based on the molecular weight, size and structural complexity of the substance. These large and complex structures assume a high 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 > 800 g/mole. Thus, it is unlikely that the substance is readily absorbed due to the steric hindrance of crossing biological membranes. According to the Guidance on information requirements and chemical safety assessment; Chapter R.11: PBT Assessment (ECHA, 2014) a molecular weight of > 700 and a calculated log Kow of > 10 can be used as evidence to conclude that a substance is unlikely to be bioaccumulative. Following the ‘rule of 5’ (Lipinski et al., 2001), developed to identify drug candidates with poor oral absorption based on criteria in partitioning (log Kow > 5), molecular weight (> 500 g/mole), the substance is considered to be poorly absorbed after oral uptake (also see Hsieh & Perkins, 1976).

The interaction between lipophilicity, bioavailability and membrane permeability is considered to be the main reason why the relationship between the bioaccumulation potential of a substance and its hydrophobicity is commonly found to be 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, 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, 2014). This assumption is supported by QSAR calculations using BCFBAF v3.01 performed for the substance. Using a validated model, which considers biotransformation, low BAF and BCF values were calculated, respectively (i.e. BCF/BAF = 0.89 L/kg; Arnot-Gobas, upper trophic; Szymoszek, 2015) clearly indicating that the substance is not bioaccumulative.The substance is outside the applicability domain of the model but it might 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 (ECHA, 2014).

As mentioned above, absorption in living organisms is expected to be low. However, hydrolysis is expected to occur to a minor extent in the gastrointestinal tract. Nevertheless possible cleavage products should be discussed here. The cleavage product 3,5,5-trimethylhexanoic acid does not undergo beta oxidation due to an uneven methyl substitution. The metabolism is suspected to occur via w- or w1-chain hydroxylation and subsequent formation of various ketoacids or dicarbonic acids, which are excreted into bile or urine or cleaved in the gut and undergo entero-hepatic circulation (ECHA Dissemination view, 2013). The second cleavage product dipentaerythritol can either remain unchanged or may further be metabolized or conjugated (e.g. glucuronides, sulfates, etc.) to polar products that are excreted in the urine. Overall, the part of the substance that have become systemically available, might be hydrolysed and the cleavage products can be further metabolized. However, due to its high molecular weight, absorption 3,5,5 trimethylhexanoic acid, mixed esters with dipentaerythritol is not likely and thus, no extensive metabolism is expected but rather direct elimination.

Conclusion

3,5,5 trimethylhexanoic acid, mixed esters with dipentaerythritol is characterized by low water solubility (< 10 µg/L), high log Kow value (> 10) and high molecular weight (> 800 g/mol). 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. However, if absorbed the substance will be hydrolyzed and the hydrolysis products undergo metabolism. Thus, it can be concluded that the log Kow indicating a potential for bioaccumulation, overestimates the true bioaccumulation potential of the substance. BCF/BAF values estimated by QSAR (BCFBAF v3.01) also indicate that the substance will not be bioaccumulative (all well below 2000 L/kg). Taking all these information into account, it can be concluded that bioaccumulation of 3,5,5 trimethylhexanoic acid, mixed esters with dipentaerythritol is unlikely to occur.