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

Long-term toxicity to fish

Description of key information

Since the chemical safety assessment according to Annex I of Regulation (EC) No 1907/2006 does not indicate the need to further investigate the long-term toxicity to fish no further long-term toxicity test to fish is proposed, in accordance with Annex IX, column 2.

Additional information

There are no experimental studies available, in which the long-term toxicity of the target substance fatty acids C18-C22 (even numbered), tetraesters with pentaerythritol to fish was assessed.

All the available studies for short-term aquatic toxicity to fish, daphnids and algae indicate no potential for acute aquatic toxicity. Furthermore, the short-term toxicity studies provide no indication that aquatic invertebrates are less sensitive than fish. Therefore, a long-term test with fish is not expected to generate significantly different results.

Additional data for long-term aquatic toxicity are available for aquatic invertebrates. In accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5 a read-across to the structurally related source substances fatty acids, C16-18 and C18-unsaturated, esters with pentaerythritol (CAS 85711-45-1) and decanoic acid, mixed esters with heptanoic acid, octanoic acid, pentaerythritol and valeric acid (CAS 71010-76-9) is applied. No long-term effects to aquatic invertebrates were detected.

In addition, aquatic toxicity of the substance is unlikely to occur due to the low bioavailability of the substance in water. 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 on organic matter. Thus, the bioavailability in the water column is reduced rapidly. The relevant route of uptake of the substance in aquatic organisms is expected to be predominantly by ingestion of particle bound substance. However, as the substance has a high molecular weight of 1370.31 – 1426.42 g/mol, 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).

Thus, the chemical safety assessment according to Annex I of Regulation (EC) No 1907/2006 does not indicate the need to investigate further the long-term toxicity to fish. In accordance with Annex IX, column 2 and for animal welfare reasons, no further long-term toxicity test to fish is therefore proposed.

References

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.