Glycerides, C18-36

Bioaccumulation: aquatic / sediment

Description of key information

The potential for bioaccumulation of Dub TGI 24 is assumed to be low based on all available data.

Additional information

Experimental bioaccumulation data are not available for Dub TGI 24. The high log Kow (> 9) as an intrinsic chemical property of the substance indicates a potential for bioaccumulation. However, the information gathered on environmental behavior, bioavailability 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 the data requirements of Regulation (EC) No 1907/2006, Annex IX to state that 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 organic matter. An assessment of bioaccumulation for possible degradation products is not considered to be necessary. Due to the ready biodegradability rapid and ultimate biodegradation under most environmental conditions is assumed. Thus, according to ECHA Guidance R.7b, no further investigation of the bioaccumulation of transformation products is required (ECHA, 2016). The low water solubility (< 0.05 mg/L at 20 °C) and high estimated log Kow (> 9) 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 concentration in the water column is reduced rapidly. The relevant route of uptake of Dub TGI 24 in aquatic organisms is expected to be predominantly by ingestion of particle bound substance. 

Metabolism of aliphatic esters

Absorption is a function of the potential for a substance to diffuse across biological membranes. The most useful parameters providing information on this potential are the molecular weight, the octanol/water partition coefficient (log Pow) value and the water solubility. The log Pow value provides information on the relative solubility of the substance in water and lipids (ECHA, 2014).

In general, molecular weights below 500 and log Pow values between -1 and 4 are favourable for oral absorption, provided that the substance is sufficiently water soluble (> 1 mg/L).

The molecular weight range of the monoglyceride is in a range that indicates absorption from the gastrointestinal tract following oral ingestion is possible. However, the partition coefficient (log Pow) for the monoglyceride and both molecular weight and log Pow for the di-and triglyceride indicate poor absorption. 

In general, mono-, di- and triglycerides (e.g. from dietary fat) undergo hydrolysis by lipases (a class of ubiquitous carboxylesterases) prior to absorption (Lehninger et al., 1998). There is sufficient evidence to assume that mono-, di- and triglycerides in general will likewise undergo enzymatic hydrolysis in the gastrointestinal tract as the first step in their absorption, distribution, metabolism and excretion (ADME) pathways.

In conclusion, the target substance Dub TGI 24 is predicted to undergo enzymatic hydrolysis. Absorption of the ester hydrolysis products is more likely rather than the parent substance. The absorption rate of the hydrolysis products is expected to be moderate-high. 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 Dub TGI 24 are expected to be initially metabolized via enzymatic hydrolysis to primarily glycerol and 2-decyltetradecanoic acid, and the monoester (2-monoacylglycerol).

Carboxylesterases are a group of ubiquitous and low substrate specific enzymes, involved in the metabolism of ester compounds in both vertebrate and invertebrate species, including fish (Leinweber, 1987; Barron et al., 1999). Glycerides, especially triglycerides, are the predominant lipid class in the diet of both marine and freshwater fish. Once ingested, they will be hydrolysed into fatty acids and glycerol by a specific group of carboxylesterase (CaE) enzymes (lipases) as reported in different fish species (Tocher, 2003).

Metabolism of enzymatic hydrolysis products

Fatty alcohols

Glycerol can be metabolised to dihydroxyacetone phosphate and glyceraldehyde-3-phosphate, which can then be incorporated in the standard metabolic pathways of glycolysis and gluconeogenesis.

Fatty acids

Fatty acids are degraded by mitochondrial β-oxidation which takes place in most animal tissues and uses an enzyme complex for a series of oxidation- and hydration reactions, resulting in the cleavage of acetate groups in the form of acetyl-CoA. The alkyl chain length is reduced by 2 carbon atoms during each β-oxidation cycle. Alternative pathways for oxidation can be found in the liver (ω-oxidation) and the brain (α-oxidation). Iso-fatty acids such as isooctadecanoic acid have been found to be activated by acyl coenzyme A synthetase of rat liver homogenates and to be metabolised to a large extent by ω-oxidation. Each two-carbon unit resulting from β-oxidation enters the citric acid cycle as acetyl-CoA, through which they are completely oxidized to CO₂. Acetate, resulting from hydrolysis of acetylated glycerides, is readily absorbed and will enter into the physiological pathways of the body and can be utilized in oxidative metabolism or in anabolic syntheses (CIR, 1983, 1987; IOM, 2005; Lehninger, 1998; Lippel, 1973; Stryer, 1996; WHO, 1967, 1974, 1975, 2001).

Data from QSAR calculation

Additional information on bioaccumulation could be gathered using the (Q)SAR model BCFBAF v3.01. The estimated BCF values for the main components of Dub TGI 24 indicate negligible bioaccumulation in organisms. When including biotransformation, low BCF/BAF values of 0.893 - 3.813 resulted (Arnot-Gobas estimate, including biotransformation, upper trophic). The applicability domain of the QSAR model (BCFBAF v3.01) consists of a descriptive domain and a structural domain. The representative component of the UVCB substance is not completely in the applicability domain of the model. With regard to the molecular weight, two representative components of the substance are within the training set of the model (MW of substances within the model training set: 68.08 - 959.17; Molecular weight of two representative components: 442.73 (Mono) and 793.36 (Di)) and one representative component of the substance is not within the training set of the model (MW of substances within the model training set: 68.08 - 959.17; Molecular weight of the representative component: 1144.00 (Tri)). The log Kow of the three representative components of the substance are outside of the applicability domain of the model (log Kow of substances within the model training set: 0.31 - 8.70, log Kow of the components: 9.49 (Mono), 20.82 (Di) and 32.56 (Tri)).

The biotransformation rate in fish is estimated using structural fragments of the representative components to estimate the half-life. In this particular case all structural fragments (six in total) necessary for the prediction of the half-life were included in the training set of the model. However, some of the fragments slightly exceeded the maximum number of instances in the training set which is not expected to have a significant impact on the final result.

Even though the applicability domain of the model is not completely met, the (Q)SAR calculations can be used as supporting indication that the potential of bioaccumulation is low. Moreover, the results support the tendency that substances with high log Kow values (> 9) 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, 2014).

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 of Dub TGI 24 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 Dub TGI 24 will not be bioaccumulative (all well below 2000 L/kg). In addition, Fatty acids are metabolised by common physiological processes. Moreover, the bioavailability of the substance in the environment is limited due to its high lipophilicity and adsorption to organic matter.
Taking all these information into account, it can be concluded that the bioaccumulation potential of Dub TGI 24 low.

References:

Barron, M. G., Charron, K.A., Stott, W.T, Duvall S.E. (1999). Tissue carboxylesterase activity of rainbow trout. Environmental Toxicology and Chemistry 18(11): 2506 - 2511.

Cosmetic Ingredient Review Expert Panel (CIR) (1983). Final report on the safety assessment of Isostearic acid. J. of the Am. Coll. of Toxicol.2(7): 61-74.

Cosmetic Ingredient Review Expert Panel (CIR) (1987) Final report on the safety assessment of oleic acid, lauric acid, palmitic acid, myristic acid, stearic acid.J. of the Am. Coll. of Toxicol.6(3):321-401.

ECHA (2014). Guidance on information requirements and chemical safety assessment, Chapter R11: PBT Assessment.

Institute of the National Academies (IOM) (2005). Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). The National Academies Press. http://www.nap.edu/openbook.php?record_id=10490&page=R1.

Lehninger, A.L., Nelson, D.L. and Cox M.M. (1998).Prinzipien der Biochemie. 2. Auflage. Heidelberg Berlin Oxford: Spektrum Akademischer Verlag.

Leinweber, F. J. (1987). Possible physiological roles of carboxylic ester hydrolases. Drug Metabolism Reviews, 18: 379-439.

Lippel, K. (1973). Activation of branched and other long-chain fatty acids by rat liver microsomes.Journal of Lipid Research 14:102-109.

Stryer, L. (1996). Biochemie. 4. Auflage. Heidelberg Berlin Oxford: Spektrum Akademischer Verlag.

Tocher, D. R. (2003). Metabolism and Functions of Lipids and Fatty Acids in Teleost Fish. Reviews in Fisheries Science 11(2): 107-184.

WHO (1967). Toxicological Evaluation of Some Antimicrobials, Antioxidants, Emulsifiers, Stabilizers, Flour-Treatment Agents, Acids and Bases: Acetic Acid and Fatty Acid Esters of Glycerol. FAO Nutrition Meetings Report Series No. 40A, B, C.

WHO (1974). Toxicological evaluation of some food additives including anticaking agents, antimicrobials, antioxidants, emulsifiers and thickening agents: Acetic Acid and Its Potassium and Sodium Salts. WHO Food Additives Series No. 5.

WHO (1975). Toxicological evaluation of some food colours, thickening agents, and certain other substances: Triacetin. WHO Food Additives Series No. 8.

WHO (1979). Castor Oil. WHO Food Additives Series No. 14.