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Environmental fate & pathways

Bioaccumulation: aquatic / sediment

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If aquatic exposure occurs, SCAE C2-C8 category members will be mainly taken up by ingestion and digested through common metabolic pathways, providing a valuable energy source for the organism, as dietary fats. These substances are thus not expected to bioaccumulate in aquatic or sediment organisms.  

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Additional information

No experimental data is available on the bioaccumulation potential of SCAE C2-C8 category members.Therefore, all available related data is combined in a Weight of Evidence (WoE), which 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 (ECHA guidance section R.7.11.5.3, page 121).

Bioaccumulation refers to uptake of a substance from all environmental sources including water, food and sediment. However, the accumulation of a substance in an organism is determined, not only by uptake, but also by distribution, metabolism and excretion. Accumulation takes place if the substance is taken up faster than it can be metabolised and/or excreted.

In the case of short chain alcohol esters (SCAE C2-C8), uptake of dissolved substance via water is expected to be low. The short chain alcohol esters (SCAE C2-C8) are poorly water soluble, have high adsorption potential (log Koc 3.0 – 7.9, MCI method, KOCWIN v2.00), but are however all regarded as readily biodegradable, with the exception of Fatty acids, C16-18 and C18 unsatd. branched and linear, butyl esters (CAS No. 163961-32-8,) which is inherently biodegradable. The aqueous environmental concentrations of the substance are therefore assumed to be low, as the substance is assumed to be eliminated in sewage treatment plants to a high extent. If fractions of this chemical were to be released in the aquatic environment, the concentration in the water phase will be reduced by rapid biodegradation and potential of adsorption to solid particles and to sediment. Additionally, the substances in the SCAE C2-C8 category have estimated low potential for dermal absorption. QSAR estimations, taking molecular weight, log Pow and water solubility into account, resulted in a dermal absorption of 0.892 – 39.9 cm/ h for the SCAE C2-C8 category members (DERMWIN v2.00, 2009). Due to low exposure concentrations through water and low dermal absorption potential, no significant uptake through the water phase can therefore be expected.

Food ingestion is likely to be the main uptake route of the SCAE C2-C8 category members in fish, since the substance may adsorb to solid particles, which could be potentially ingested by fish. Also for sediment-dwelling organisms the main uptake route will be ingestion of contaminated sediment. In the case of ingestion, SCAE C2-C8 category members are predicted to undergo metabolism. Esters of primary alcohols, containing from 1 to 18 carbon atoms, with fatty acids, containing from 2 to 18 carbon atoms, have been shown to be hydrolysed by pancreatic lipases in a study by Mattson and Volpenhein (Mattson and Volpenhein, 1972). Measured rates of enzyme catalysed hydrolysis varied between 2 and 5 µeq/min/mg enzyme for the different chain lengths (IUCLID section 7.1.1, Mattson and Volpenhein, 1972; and references therein). The longer esters possibly present in the UVCB substance Fatty acids, lanolin, isopropyl esters (CAS 63393-93-1), are also expected to be hydrolysed. Only moderate differences in the rate of hydrolysis were observed for different long chain saturated and unsaturated fatty-acid esters, in studies investigating the fatty acid specificity of pancreatic lipases (Macrae and Hammond, 1985; and references therein). Exceptionally poor substrates were esters of fatty acids containing a double bond or a bulky substituent close to the carboxyl group, probably due to steric reasons. Fatty acids, lanolin, isopropyl esters (CAS 63393-93-1) only contains saturated fatty acids and branching may only occur on the penultimate or the ante-penultimate carbon atom, i.e. far from the carboxyl group. All esters of the SCAE C2-C8 category are thus expected to be hydrolysed by lipases. The resulting free fatty acids and alcohols are absorbed from the intestine into the blood stream. The alcohols are metabolised primarily in the liver through a series of oxidative steps, finally yielding carbon dioxide (Berg, 2001; HSDB)

Fatty acids are either metabolised via the beta-oxidation pathway in order to generate energy for the cell or reconstituted into glyceride esters and stored in the fat depots in the body (Berg et al., 2001). For fatty acids up to C22, beta-oxidation generally takes place in the mitochondria, resulting in the final product acetyl-CoA, which directly enters the citric acids cycle (Berg, 2002). Beta-oxidation of longer fatty acids takes place in the peroxisomes and is incomplete (Reddy and Hashimoto, 2001; Singh et al., 1987; Le Borgne and Demarquoy, 2012; and references therein). It gives rise to medium chain acyl-CoA, which are then taken in charge by the carnitine octanoyl transferase and converted into acyl-carnitine that can leave the peroxisome and, at least for some of them, may be fully oxidized in the mitochondria (Le Borgne and Demarquoy, 2012; and references therein). Peroxisomalβ-oxidation has also been shown to take place in fish, mussels and algae (Rocha et al., 2003; and references therein; Frøyland et al., 2000; Bilbao et al., 2009; Winkler et al., 1988). Metabolic pathways in fish are generally similar to those in mammals. Lipids and their constituents, fatty acids, are in particularly a major organic constituent of fish and play major roles as sources of metabolic energy (Tocher, 2003).

Studies conducted with rats indicate that the main route of excretion in rats is via expired air as CO2, and the second route of excretion is by biliary excretion and faeces. Exemplarily, experimental data of ethyl oleate (the ethyl ester of oleic acid) support this assumption: 14C-labeled carbon of 5 mL/kg of ethyl oleate (CAS No. 111-62-6) was rapidly excreted in respiration CO2 (approximately 70%), faeces (7 -10%), and urine (1-2%), with essentially complete elimination by 72 hours after administration (Bookstaff, 2003).

In conclusion, SCAE C2-C8 category members will be mainly taken up by ingestion and are digested through common metabolic pathways, providing a valuable energy source for the organism, as dietary fats. These substances are thus not expected to bioaccumulate in aquatic or sediment organisms.

Biotransformation and biomagnification are processes that may occur once a chemical has bioaccumulated. As these chemical substances are readily biodegradable and are considered to be rapidly metabolised, SCAE C2-C8 category members will not be biomagnified within the food chain. 

Hence, as theSCAE C2-C8 category membersdo not pose a risk to organisms in regard to bioaccumulation/biomagnification, in addition toreasons of animal welfare, no further testing is neither required nor proposed.The available literature, supporting the assessment of bioaccumulation are presented in the IUCLID technical dossier and associated chemical safety report in a Weight of Evidence (WoE) approach, which 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 (ECHA guidance section R.7.11.5.3, page 121).

 

References:

Berg, J.M., Tymoczko, J.L. and Stryer, L., 2002, Biochemistry, 5thedition, W.H. Freeman and Company

Bilbao, E., Cajaraville, M.P., Cancio, I. (2009), Cloning and expression pattern of peroxisomal β-oxidation genes palmitoyl-CoA oxidase, multifunctional protein and 3-ketoacyl-CoA thiolase in mussel Mytilus galloprovincialis and thicklip grey mullet Chelon labrosus, Gene, 443(1-2): 132-42

Bookstaff, R.C, Pai Bir, S., Bharaj, S.S., Kelm, G.R., Kulick, R.M., Balm, T.K., Murray, J.V. (2003) The safety of the use of ethyl oleate in food is supported by metabolism data in rats and clinical safety data in humans, Regulatory Toxicology and Pharmacology, 37, 133-148

Le Borgne, F., Demarquoy, J. (2012): Interaction between peroxisomes and mitochondria in fatty acid metabolism, Open Journal of Molecular and Integrative Physiology, 2012, 2, 27-33

Frøyland, Lie, Berge (2000), Mitochondrial and peroxisomalβ-oxidation capacities in various tissues from Atlantic salmon Salmo salar, Aquaculture Nutrition, 6 (2): 85-89

HSDB – Hazardous Substances Data Bank, Toxnet Home, National Library of Medicinehttp: //toxnet. nlm. nih. gov/cgi-bin/sis/htmlgen?HSDB

Macrae, A.R., Hammond, R.C. (1985) Present and future applications of lipases, Biotechnology and Genetic Engineering Reviews, 3: 193-217

Mattson, F.H. and Volpenheim, R.A. (1972): Relative rates of hydrolysis by rat pancreatic lipase of esters of C2-C18 fatty acids with C1-C18 primary n-alcohols,Journal of Lipid Research, 10, 1969

Poirier, Y., Antonenkov, V.C., Glumoff, T, Hiltunen, K. (2006) Peroxisomal β-oxidation - A metabolic path- way with multiple functions Biochimica et Biophysica Acta 1763 (12), 1413-1426

Reddy and Hashimoto (2001) Peroxisomal beta-oxidation and peroxisome proliferator-activated receptor alpha: An adaptive metabolic System, Annual Review of Nutrition, 21, 193-230

Rocha, M.J., Rocha, E., Resende, A.D., Lobo-da-Cunha (2003) Measurement of peroxisomal enzyme activities in the liver of brown trout (Salmo trutta), using spectrophotometric methods, BMC Biochemistry, 4:2,doi:10.1186/1471-2091-4-2

Singh, H., Derwas, N. and Puolos, A. (1987) Beta-oxidation of very-long-chain fatty acids and their coenzyme A derivatives by human skin fibroblasts, Arch Biochem Biophys, 254(2): 526-33

Winkler, U., Säftel, W., Stabenau, H. (1988), beta-Oxidation of fatty acids in algae: Localization of thiolase and acyl-CoA oxidizing enzymes in three different organisms, Planta, 175(1): 91-98