2,2-bis[[(1-oxoisononyl)oxy]methyl]-1,3-propanediyl diisononanoate

Bioaccumulation: aquatic / sediment

Description of key information

If aquatic exposure occurs, 2,2-bis[[(1-oxoisononyl)oxy]methyl]-1,3-propanediyl diisononanoate (CAS 93803-89-5) will be mainly taken up by ingestion but absorption of is expected to be low based on the molecular weight, size and structural complexity of the substance. 2,2-bis[[(1-oxoisononyl)oxy]methyl]-1,3-propanediyl diisononanoate is 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 2,2-bis[[(1-oxoisononyl)oxy]methyl]-1,3-propanediyl diisononanoate (CAS 93803-89-5). In principle, the estimated high log Kow value > 10 (KOWWIN v1.68) indicate 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 IX concluding that the substance is likely to show negligible bioaccumulation potential in aquatic organisms.

 

Environmental behaviour

2,2-bis[[(1-oxoisononyl)oxy]methyl]-1,3-propanediyl diisononanoateis characterized by a high partition coefficient (calculated log Kow > 10, KOWWIN v1.68) indicating that the substance is highly lipophilic. The log Koc values of the main components of > 5 indicates that the substance will adsorb to suspended organic particles, dissolved organic matter (DOM) and to some degree biota in the aquatic environment (e.g. Jaffé, 1991). Considering the high 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 2,2-bis[[(1-oxoisononyl)oxy]methyl]-1,3-propanediyl diisononanoateis expected to be low based on the molecular weight, size and structural complexity of the substance. These large and complex structures 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 high molecular weight of 697.04 g/mol.Thus, it is unlikely that they are 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 in partitioning (log Kow > 5), molecular weight (> 500 g/mol), 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, which have been calculated for the major components of the UVCB 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, 2008a). 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 from 0.89 and 5.79 L/kg, respectively (Arnot-Gobas, upper trophic; Hopp, 2011) 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, 2012).

 

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 and after systemic uptake. Nevertheless possible cleavage products should be discussed here. The other 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 omega- and omega- 1-oxidation, which lead to formation of various polar metabolites capable of excretion in the urine (WHO, 1998). The second cleavage product pentaerythritol is absorbed rapidly but excreted unchanged. DiCarlo et al. 1965 reported that 10 mg/kg C14-labled PE orally administered to mice was absorbed and excreted rapidly from the gastrointestinal tract. Almost half of the administered dose left the gastrointestinal tract within 15 minutes and 68% of the dose appeared as unchanged PE in the urine and faeces after 4 hours already. Overall, the part of 2,2-bis[[(1-oxoisononyl)oxy]methyl]-1,3-propanediyl diisononanoate that have become systemically available, might be hydrolysed and the cleavage products can be further metabolized.

 

Conclusion

2,2-bis[[(1-oxoisononyl)oxy]methyl]-1,3-propanediyl diisononanoateis characterized by a low water solubility (< 0.05 mg/L), high log Kow (> 10) and a high molecular weight (697.04 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 2,2-bis[[(1-oxoisononyl)oxy]methyl]-1,3-propanediyl diisononanoateis unlikely to occur.

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