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Environmental fate & pathways

Bioaccumulation: aquatic / sediment

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Description of key information

PFAE fumarates category members are not expected to bioaccumulate in aquatic or sediment organisms and consequently secondary poisoning does not pose a risk.

Key value for chemical safety assessment

Additional information

No experimental data evaluating the bioaccumulation potential of the PFAE fumarates category members are available. Therefore, all available related data is combined 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 (ECHA, 2012c).

Environmental behaviour

The members of the PFAE fumarates Category consist of main components with estimated high partition coefficients (calculated log Kow ≥ 8, for the majority of substances > 10). Based on the high log Kow and the high measured water insolubility, determined to be below the detection limits of the used methods of 0.15 mg/l and 0.05 mg/l, respectively, one can conclude that the substances within this category are lipophilic (in nature). In addition, the calculated log Koc values above 4 (in most cases > 5) indicate that the substances or the main components of the substances (in case of UVCBs) will adsorb to suspended organic particles, dissolved organic matter (DOM) and to some degree biota in the aquatic environment (e.g., see Jaffé, 1991). The substances are considered to be readily biodegradable or readily biodegradable, but failing 10-day window and therefore have shown enhanced ultimate biodegradability, which indicates that the substances will neither be persistent in the aquatic nor the terrestrial compartment. Hence the concentration of the category members in the aquatic environment is expected to be low as they are in general effectively removed in conventional STPs either by biodegradation or by sorption to biomass. Indirect application of the substances via sludge application can be excluded, as the sludge will be incinerated. Considering this, one can assume that the availability of the substances in the aquatic environment are generally low, which reduces the probability of adsorption and uptake from the surrounding medium into organisms (Björk, 1995, Haitzer et al., 1998).

If environmental concentrations facilitate exposure, the uptake of the category members from medium into organisms is expected to be low based on the molecular weight, size and structural complexity of the substances. The category members are fumaric acid esters with two side chains of C8 to C22 carbon length. These large and complex structures in conjunction with their stereoisomerism around the butenedioic acid part 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, which they assumed to be related to the enhancement of the entropy factor on membrane permeability of chemicals. This concludes a high probability that a substance may encounter the membrane in a conformation which does not enable the substance to permeate.

Furthermore, several of the category members consist of main components featuring high molecular weights of 500 to 733 g/mol. Even if dermal adsorption of substances cannot per se be excluded, it is conducive to say that with such molecular weights they may not be readily taken up due to the steric hindrance of crossing biological membranes.

This interaction between hydrophobicity, 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 (Dimitrov et al., 2002; Nendza & Müller, 2007; Arno and Gobas 2003). Substances with log Kow values above 10, which have been calculated for almost all substances and main components of substances within the Fumarates category, are, however, again considered to have a low bioaccumulation potential (Nendza & Müller, 2007; 2010). Furthermore, for those substances with a log Kow value >10 it is recognized by the relevant authorities that it is unlikely that they accomplish the pass level of being bioaccumulative according to OECD criteria for the PBT assessment (log BCF = 2000; ECHA, 2011). Regarding the members of the Fumarates category, this assumption is supported by QSAR calculations using BCFBAF v3.01 performed for the category members and its main components (Hopp, 2011 a; b; c; d; e; f). BCF values were calculated to be between 986 and 3.16 l/kg (regression based method). A model which considered biotransformation calculated even lower BCF and BAF values between 0.90 - 0.89 and 10.1 - 0.89 l/kg, respectively (Arnot-Gobas, upper trophic). Even though the members of the Fumarates Category are, due to their high calculated log Kow values, in most cases outside the applicability domain of the used model (model training set is constituted of substances with log Kow values in the range of 0.31 to 8.70), the calculations (especially the low BCF values calculated using the Arnot-Gobas method) reflect the rapid biotransformation assumed for the category members.

Metabolism of aliphatic esters and metabolites

The log Pow of > 10 suggests that PFAE fumarates category member are favourable for absorption by micellar solubilisation, as this mechanism is of importance for highly lipophilic substances (log Pow > 4), which are poorly soluble in water (< 1 mg/l). After oral ingestion, the members of the PFAE fumarates category undergo stepwise hydrolysis of the ester bonds by gastrointestinal enzymes (Lehninger, 1970; Mattson and Volpenhein, 1972). The cleavage products fatty alcohol (C8-C22) and fumaric acid (CAS 110-17-8) are formed. Both metabolites exhibit no potential for bioaccumulation.


Fumarates are biotransformed to dicarboxylic acids and the corresponding alcohol component by the ubiquitous carboxylesterase enzymes in aquatic species. Based on the rapid metabolism it can be concluded that the high log Kow, which indicates a potential for bioaccumulation, overestimates the true bioaccumulation potential of the Fumarates category members. Taking all these information into account, it can be considered that bioaccumulation of Fumarates Category members is unlikely to occur.

In addition, according to Annex XI, section 2 of Regulation (EC) No. 1907/2006, it has to be considered that it is technically impossible to determine a reliable BCF value, due to the very low water solubilities of the category members. The water solubilities were determined to be lower than the detection limit of the available analytical method (i.e. 5 μg/l and 15 μg/l, respectively) therefore this would infer that no reliable test results can be retrieved for the analysis of the substance in the aqueous phase if a bioaccumulation test (OECD 305) would be conducted (OECD 305; Verhaar et al., 1999). According to “Guidance on information requirements and chemical safety assessment; Chapter R.7c” (ECHA, 2012c), a dietary accumulation test with fish may be used in cases where an OECD 305 test is not suitable; however, there is no official guideline available and based on the broad knowledge about the metabolism of fatty acid esters after ingestion, as mentioned above, no further testing is deemed necessary.

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