Registration Dossier

Environmental fate & pathways

Bioaccumulation: aquatic / sediment

Currently viewing:

Administrative data

Link to relevant study record(s)

Description of key information

Fatty acids, C16-C18, methyl esters is expected to show low bioaccumulation potential

Key value for chemical safety assessment

Additional information

5.3.1 Aquatic bioaccumulation- SCAE Me category

No experimental data evaluating the bioaccumulation potential of the SCAE Me category members are available. All substances within the SCAE Me category have log Kow values above 3, suggesting potential to bioaccumulate in biota. Nevertheless, the information gathered on environmental behaviour and metabolism in combination with the QSAR-estimated BCF values provide enough evidence (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. 1907/2006, Annex IX) to state that these substances are likely to show low bioaccumulation potential.


Intrinsic properties and fate


All substances included in the SCAE Me category are readily biodegradable. According to the Guidance on information requirements and chemical safety assessment, Chapter R.7b, readily biodegradable substances can be expected to undergo rapid and ultimate degradation in most environments, including biological Sewage Treatment Plants (STPs)(ECHA, 2008). Therefore, after passing through conventional STPs, only low concentrations of these substances are likely to be (if at all) released into the environment.

Most of the substances within the SCAE Me category are insoluble in water (water solubility < 1 mg/L). The Guidance on information requirements and chemical safety assessment, Chapter R7.B (ECHA, 2008) states that once insoluble chemicals enter a standard STP, they will be extensively removed in the primary settling tank and fat trap and thus, only limited amounts will pass through into the secondary treatment (biological). On the other hand, octanoic acid, methyl ester (CAS No. 111-11-5), decanoic acid, methyl ester (CAS No. 110-42-9) and dodecanoic acid, methyl ester, due to their higher solubility in water (water solubilities of 64.4, 10.6 and 7.7 mg/L) are expected to pass the primary treatment and get in contact with activated sludge organisms. Nevertheless, once this contact takes place, considering the available log Koc values > 3 and the log Kow for all SCAE Me category members (> 3), adsorption to activated sludge can be expected to be an important physical elimination process from water in sewage treatment plants (STPs)(Guidance on information requirements and chemical safety assessment, Chapter R.7a, (ECHA, 2008)). The remaining fraction available in the water will be extensively biodegraded (due to ready biodegradability). Thus, discharged concentrations of these substances into the aqueous compartment are likely to be very low.


Should the substances be released into the water phase, most of them will tend to bind to sediment and other particulate organic matter, due to their hydrophobicity and expected high adsorption potential, and therefore, the actual dissolved fraction available to fish via water will be reduced (Mackay and Fraser, 2000). The main route of exposure for aquatic organisms such as fish will be via food ingestion or contact with suspended solids. For water soluble substances, uptake via the gills and/or skin due to direct contact with water will be the most relevant route of exposure.


QSAR data


Additional information on the bioaccumulation of SCAE Me in fish species is available. Estimated bioconcentration (BCF) and bioaccumulation (BAF) values were calculated for all substances using the BCFBAF v3.01 program (Estimation Programs Interface Suite™ for Microsoft® Windows v 4.10., US EPA), including biotransformation rates (Arnot-Gobas method). In the case of the UVCB substances, the calculations were performed on the main fatty acid components, as representative structures for each UVCB. All SCAE Me substances (or at least their main FA components) are within the applicability domain of the QSAR model (log Kow 0.31-8.70) and therefore, provide valid supporting information to be considered in the overall bioaccumulation assessment of these substances.

Within the category, BCF values tend to increase with increasing fatty acid C-chain lengths from C12 (154.3 L/kg) up to C14 (201 L/kg), to decrease again at longer C-chain lengths (C16, 95.6 L/kg and C18, BCF 23.3-29 L/kg), with the exception of the C18 unsaturated fatty acid component, with a BCF of 117.8 L/kg. On the other hand, BAF values increase as the fatty acid C-chain length increases, ranging from 154 L/kg (C12) up to 500 L/kg (C18 unsaturated).

The difference in the pattern for BCF and BAF values across the category can be explained by the exposure route(s) considered for the estimation: BCF calculations reflect the bioaccumulation potential after uptake via water, whereas the BAF gives an indication of the bioaccumulation when all exposure routes (water, food, etc.) are taken into account.

The obtained results indicate that the members of the SCAE Me category are likely to show low (shorter C-chain lengths) to moderate (longer C-chain lengths) bioaccumulation potential. According to Regulation (EC) No. 1907/2006, Annex XIII, 1.1.2, a substance only fulfils the bioaccumulation criterion (B) when BCF values are > 2000. Even though this condition is preferred to be confirmed with experimental data, in this case the estimated QSAR-based BCFs provide sufficient reliable evidence which suggests that the SCAE Me category members will not be bioaccumulative.


Biotransformation and metabolism


After lipid content, the degree of biotransformation seems to be the most relevant factor regarding the bioaccumulation of organic chemicals in aquatic organisms (Katagi, 2010). Biotransformation consists in the conversion of a specific substance into another/others (metabolites) by means of enzyme-catalyzed processes (ed. van Leeuwen and Hermens, 1995).


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).Fatty acid methyl esters are hydrolysed to the corresponding alcohol (methanol) and fatty acid by esterases (Fukami and Yokoi, 2012). Particularly in fish rapid metabolism rates of two methyl esters (haloxyfop methyl ester and fluroxypyr methylheptyl ester) have been observed in vitro (fish liver homogenates) with half-lives ≤ 5 minutes and low predicted BCF values (Murphy and Lutenske, 1990; Cowan-Elsberry et al., 2008). Furthermore,in vivo studies conducted with esters, including a methyl ester (according to OECD 305) resulted in experimental fish BCFs ranging from 1 to 70, even when the log Kow values of these substances are above 3, indicating once again rapid metabolism (Rodger and Stalling, 1972; Barron et al., 1989; Barron et al., 1990).

According to the Guidance on information requirements and chemical safety assessment, Chapter R.7c (ECHA, 2008), even though ready biodegradability does not per se preclude bioaccumulation potential, generally (depending on exposure and uptake rates) ready biodegradable substances are likely to be rapidly metabolised, and therefore, concentrations stored in aquatic organisms will tend to be low.

Regarding the biotransformation products of SCAE Me(s), methanol will partially tend to evaporate from water surfaces (Henry's Law Constant of 4.55x10-6 atm m3/mole (Gaffney et al., 1987)) or stay in the water phase (low adsorption potential to sediment and organic particles according to a Koc of 2.75 (Schuurmann et al, 2006)), in which rapid biodegradation is expected to occur (92% biodegradation in 14 days; NITE, Japan, 2012). Therefore, its bioavailability to aquatic organisms will be generally low. Methanol is a naturally occurring compound in living organisms. It is known to be metabolised and further excreted in the form of CO2and H2O in several species such as mammals (ICPS, 2002). The log Kow value of this substance (-0.77, Hansch et al., 1995) indicates that bioaccumulation in biota is not expected. In fish (Leuciscus idus), this was confirmed by a test in which a measured BCF < 10 was obtained for methanol (Freitag et al., 1985).

On the other hand, fatty acids are naturally occurring components in living organisms (mammals, aquatic organisms, earthworms, plants, etc.), which are known to be metabolised quickly and participate in ubiquitous standard physiological processes (e. g. citric acid cycle, sugar synthesis and lipid synthesis)(Hochachka et al., 1977; Jump, 2002). In fish species, fatty acids are the most important energy source resulting in the release of acetyl CoA and NADH (through β-oxidation) and eventually, via the tricarboxylic cycle, the production of metabolic energy in the form of ATP. This fatty acid-catabolism pathway is the predominant source of energy related to growth, reproduction and development from egg to adult fish (Tocher, 2003). A similar metabolic pathway is observed in mammals (see section 7.1.1 Basic toxicokinetics).





The substances included in the SCAE Me category are not expected to be bioaccumulative. Due to their readily biodegradable nature, extensive degradation of these substances in conventional STPs will take place and only low concentrations are expected to be released (if at all) into the environment. Once present in the aquatic compartment, further biodegradation will occur and, depending on their log Kow, water solubility and adsorption potential, the SCAE Me(s) will be bioavailable to aquatic organisms such as fish mainly via water or on the other hand via feed and contact with suspended organic particles. After uptake by fish species, extensive and fast biotransformation of the SCAE Me(s) by carboxylesterases into fatty acids and methanol is expected. Fatty acids will be further used by these organisms as their main source of energy throughout all the different life stages (early development, growth, reproduction,etc.). Rapid metabolism of analogue ester compounds (involving hydrolysis into fatty acids and methanol) in fish has been observed in vitro, with half-lives in fish liver homogenates below 6 minutes. In vivo fish tests reported BCF values ranging from 1 to 70 for similar ester substances, supporting the argument that rapid metabolism takes place even when log Kow values are above the trigger value of 3. The supporting BCF/BAF values estimated with the BCFBAF v3.01 program also indicate that these substances will not be bioaccumulative (all well below 2000).

The information above provides strong evidence supporting the statement that rapid metabolism and low bioaccumulation potential can be expected for the members of the SCAE Me category (detailed information on the results of a more extensive literature search can be found as an attachment).



Barron, M.G., Schultz, I.R., Hayton, W.L. (1989). Presystemic branchial metabolism limits di-2-ethyl-hexylphtalate accumulation in fish. Toxicology and Applied Pharmacology, 98, pp. 48-57


Barron , M.G., Mayes, M.A., Murphy, P.G., Nolan, R.J. (1990). Pharmacokinetics and metabolism of triclopyr butoxyethyl ester in coho salmon. Aquatic Toxicology, 16: 19-32


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


Cowan-Ellsberry, C.E., Dyer, S.D., Erhardt, S., Bernhard, M.J., Roe, A.L., Dowty, M.E. and Weisbrod, A.V. (2008). Approach for extrapolating in vitro metabolism data to refine bioconcentration factor estimates. Chemosphere, 70(10): 1804-1817


European Chemicals Agency (ECHA, 2008). Guidance on information requirements and chemical safety assessment, Chapter R.7a: Endpoint specific guidance


European Chemicals Agency (ECHA, 2008). Guidance on information requirements and chemical safety assessment, Chapter R.7b: Endpoint specific guidance


European Chemicals Agency (ECHA, 2008). Guidance on information requirements and chemical safety assessment, Chapter R.7c: Endpoint specific guidance


European Chemicals Agency (ECHA, 2008). Guidance on information requirements and chemical safety assessment, Chapter R.11: PBT Assessment


Freitag, D. (1985). Environmental hazard profile of organic chemicals: An experimental method for the assessment of the behavior of organic chemicals in the ecosphere by means of simple laboratory tests with 14C labeled chemicals. Chemosphere, 14: 1589-1616


Fukami, T. and Yokoi, T. (2012). The Emerging Role of Human Esterases. Drug Metabolism and Pharmacokinetics, Advance publication July 17th, 2012.


Gaffney, J.S., Streit, G.E., Spall, W.D. and Hall, J.H. (1987).Beyond acid rain. Do soluble oxidants and organic toxins interact with SO2 and NOx to increase ecosystem effects?. Environmental Science and Technology, 21(6): 519-524


Hansch, C., Leo, A., Hoekman, D. (1995).Exploring QSAR - Hydrophobic, Electronic, and Steric Constants. Washington, DC: American Chemical Society., p. 3


Hochachka, P.W., Neely, J.R., Driedzic, W.R. (1977). Integration of lipid utilization with Krebs cycle activity in muscle. Fed Proc., 36(7): 2009-2014

International Programme on Chemical Safety, ICPS (2002). Poisons Information Monograph 335, Methanol.

Jump, D.B. (2002). The Biochemistry of n-3 Polyunsaturated Fatty Acids. The Journal of Biological Chemistry, 277: 8755-8758


Katagi, T. (2010). Bioconcentration, bioaccumulation, and metabolism of pesticides in aquatic organisms. Reviews of Environmental Contamination and Toxicology, 204: 1-132


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


Mackay, D. and Fraser, A. (2000). Bioaccumulation of persistent organic chemicals: mechanisms and models. Environmental Pollution, 110: 375-391


Murphy, P.G. and Lutenske, N.E. (1990). Bioconcentration of haloxyfop-methyl in bluegill (Lepomis macrochirusRafinesque). Environment International, 16(3): 219-230


Japanese National Institute of Technology and Evaluation. Biodegradation in water: screening tests. Available at 24th August 2012)


Rodger, C.A. and Stalling, D.L. (1972). Dynamics of an ester of 2,4-D in organs of three fish species. Weed Science, 20:101-105


Schuurmann, G., Ebert, R.U. and Kuhne, R. (2006).Prediction of the Sorption of Organic Compounds into Soil Organic Matter from Molecular Structure. Environmental Science and Technology, 40(22): 7005-7011


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


US EPA (2011). Estimation Programs Interface Suite™ for Microsoft® Windows v 4.10. BCFBAF v3.01. United States Environmental Protection Agency, Washington, DC, USA.


US EPA (2011). Estimation Programs Interface Suite™ for Microsoft® Windows v 4.10. KOCWIN v2.00. United States Environmental Protection Agency, Washington, DC, USA.


Van Leeuwen, C.J. and Hermens, J.L.M. (ed), 1995. Risk Assessment of Chemicals: An Introduction. Kluwer Academic Publishers, Dordrecht, the Netherlands