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EC number: 226-641-8 | CAS number: 5444-75-7
Endpoint summary
Administrative data
Description of key information
Additional information
No experimental data evaluating the bioaccumulation potential of 2-ethylhexyl benzoate (CAS No. 5444-75-4) is available. The substance exhibits a log Kow value of 6.21, suggesting potential to bioaccumulate in biota. However, the information gathered on environmental behaviour and metabolism in combination with 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 2-ethylhexyl benzoate is likely to show no bioaccumulation potential.
Intrinsic properties and fate
2-ethylhexyl benzoate is readily biodegradable (Dickinson, 2008). 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.
Furthermore, the substance exhibits a log Koc value > 3 and is poorly water soluble (water solubility 0.4 mg/L in aqua bidest). 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 get in contact with activated sludge organisms. Nevertheless, once this contact takes place, these substances are expected to be removed from the water column to a significant degree by adsorption to sewage sludge (Guidance on information requirements and chemical safety assessment, Chapter R.7a, (ECHA, 2008)) and the rest 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, due to their hydrophobicity and expected high adsorption potential, they will tend to bind to sediment and other particulate organic matter, and therefore, the actual dissolved fraction available to fish via water will be reduced. Thus, the main route of exposure for aquatic organisms such as fish will be via food ingestion or contact with suspended solids.
QSAR data
Additional information on the bioaccumulation of 2-ethylhexyl benzoate 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). The substance fits within the applicability domain of the QSAR model (log Kow 0.31-8.70) and therefore, these calculations provide valid supporting information to be considered in the overall bioaccumulation assessment of this substance.
For 2-ethylhexyl benzoate, the regression based estimate results in a BCF estimation of 5810 L/kg, indicating bioaccumulation potential. In contrast, BCF and BAF values, estimated using the Arnot-Gobas model, including biotransformation, results in considerable lower values (BCF: 184 L/kg and BAF: 189 L/kg). 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 low BCF/BAF values calculated using the Arnot-Gobas method reflect the rapid biotransformation assumed for this substance and are considered as more reliable for the assessment of bioaccumulation of this substance, compared to the log Kow based model.
The obtained result indicates that 2-ethylhexyl benzoate is likely to show no bioaccumulation potential. According to Regulation (EC) No. 1907/2006, Annex XIII, 1.1.2, a substance only fulfills 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 BCF/BAF values (Arnot-Gobas estimation) provide sufficient reliable evidence which suggests that 2-ethylhexyl benzoate will not be bioaccumulative.
Metabolism of 2-ethylhexyl benzoate and metabolites
After absorption, 2-ethylhexyl benzoate is expected to be enzymatically hydrolysed in vivo by the ubiquitary enzyme carboxylesterase, yielding the corresponding alcohol and benzoic acid (Jones, 1956).
The metabolism of alcohols in fish was intensively studied by Reimers et al. (2004). They isolated and characterized two cDNAs from the zebra fish, Danio rerio, encoding ADHs, which showed specific metabolic activity in in-vitro assays with various alcohol components ranging from C4 to C8. The emerging aldehydes were shown to be further oxidized to the corresponding fatty acid by ALDH enzymes. The most effective ALDH2, which is mainly located in the mitochondria of liver cells showed a similarity of 75% to mammalian ALDH2 enzymes and a similar catalytic activity (also see Nilsson, 1988). The same metabolic pathway was shown for longer chain alcohols, such as stearyl and oleyl alcohol in the intestines of rats (Sieber et al., 1974).
In mammals, benzoic acid is primarily metabolized to its glycine conjugate, hippuric acid, which is readily excreted via the renal organic anion transport system. Although, metabolization of benzoic acid in fish is different compared to mammals (James and Pritchard, 1987), benzoic acid is clearly established as not-bioaccumulative (OECD, 2001).
Summarizing, 2-ethylhexyl benzoate is expected to be rapidly hydrolyzed to benzoic acid and 2-ethylhexanol. Both hydrolysis products are supposed to be satisfactorily metabolized in aquatic organisms. Therefore, no potential for bioaccumulation is to be expected.
Conclusion
2-ethylhexyl benzoate is not expected to be bioaccumulative. Due to its readily biodegradable nature, extensive degradation of this substance 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, due to the high log Kow, low water solubility and high adsorption potential, the 2-ethylhexyl benzoate will be bioavailable to aquatic organisms such as fish mainly via feed and contact with suspended organic particles. After uptake by fish species, extensive and fast biotransformation of the substance by carboxylesterases into benzoic acid and the corresponding alcohol is expected. The supporting BCF/BAF values estimated with the BCFBAF v3.01 program, Arnot-Gobas model including biotransformation, also indicate that this substance will not be bioaccumulative (all well below 2000 L/kg).
References
ECHA. 2008a. Guidance on information requirements and chemical safety assessment – Part C: PBT assessment. European Chemicals Agency, Helsinki
ECHA. 2008b. Guidance on information requirements and chemical safety assessment – Chapter 7c: Endpoint specific guidance. European Chemicals Agency, Helsinki
James MO and Pritchard JB, 1987. In vivo and in vitro renal metabolism and excretion of benzoic acid by a marine teleost, the southern flounder. Drug Metab Dispos. 1987 Sep-Oct;15(5):665-70.
Jones P. S., Thigpen D., Morrison J. L., and Richardson A.P. (1956) p-hydroxybenzoic acid esters as preservatives. III. The physiological disposition of p-hydroxybenzoic acid and its esters.J. of the Amer. Pharm. Assoc., 45(1),268-273.
Nilsson GE. 1988. A comparative study of aldehyde dehydrogenase and alcohol dehydrogenase activities in crucian carp and three other vertebrates: apparent adaptations to ethanol production. J Comp Physiol B 158(4): 479-85
OECD. 2001. SIDS Initial Assessment Report for 13th SIAM. Benzoate Category. UNEP-Publications.
Reimers MJ, Hahn ME, Tanquay RL. 2004. Two zebrafish alcohol dehydrogenases share common ancestry with mammalian class I, II, IV, and V alcohol dehydrogenase genes but have distinct functional characteristics. J Biol Chem 279(37): 38303-38312
Sieber SM, Cohn VH, Wynn WT. 1974. The entry of foreign compounds into the thoracic duct lymph of the rat. Xenobiotica 4(5): 265-284
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