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Environmental fate & pathways

Bioaccumulation: aquatic / sediment

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Description of key information

Bis(2-propylheptyl) hexanedioate does not significantly accumulate in organisms. 

Key value for chemical safety assessment

BCF (aquatic species):
27 L/kg ww

Additional information

Since no study for assessing the bioaccumulation potential of Bis(2-propylheptyl) hexanedioate, DPHA) is available, in accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5 Grouping of substances, a read-across to the structurally related source substance Bis(2-ethylhexyl) adipate (CAS 103-23-1, DEHA) was conducted. The only structural difference between the source substance and the target substance is the slightly (one C-atom) longer carbon chain of the branched fatty alcohol component of the target substance. The read across is justified due to (i) the similarity of structure and functional groups and accordingly (ii) similar physico-chemical properties resulting in a similar environmental fate and ecotoxicity profile (for details see justification document in chapter 13).

The bioaccumulation of the source substance in aquatic organisms was examined in a bioconcentration test with bluegill sunfish (Lepomis macrochirus) using 14C-labelled DEHA (Felder et al. 1986). The test was carried out for 42 days. Concentrations of DEHA in water, whole fish, viscera, and fillet were analyzed at intervals during the test. After the first 35 days of exposure, the remaining fish were exposed to clean water for an additional 14 days and concentrations of DEHA were measured in the fish at intervals. A whole fish bioconcentration factor (BCF) of 27 was reported at day 35. Following exposure to clean water, a depuration rate for DEHA of 0.26/day (t 1/2 = 2.7 days) was determined. The results imply that the accumulation of DEHA is low despite a high log Pow (log Pow = 8.94), most likely due to rapid metabolization. Furthermore, when transferred to freshwater, the substance is apparently rapidly and extensively excreted from the fish. This experimental result can be easily explained by the general enzymatic processes, which are numerously published in the scientific literature: If taken up by living organisms, aliphatic esters such as DEHA and DPHA will be initially metabolized via enzymatic hydrolysis to the respective dicarboxylic acid and alcohol components as would dietary fats (e.g., Linfield 1984, Lehninger 1970, Mattson and Volpenhein 1972). The hydrolysis is catalyzed by carboxylesterases and esterases, with B-esterases located in hepatocytes of mammals being the most important (e.g., Heymann 1980). Carboxylesterase activity has also been reported from a wide variety of tissues in invertebrates and fishes (e.g., Barronet al.1999, Wheelocket al.2008). In fish, the high catalytic activity, low substrate specificity and wide distribution of the enzymes in conjunction with a high tissue content lead to a rapid biotransformation of aliphatic esters, which significantly reduces its bioaccumulation potential (Lech and Melancon 1980, Lech and Bend 1980).

2-propylheptanol and adipic acid are the expected hydrolysis products from the enzymatic reaction catalyzed by carboxylesterase. These metabolites exhibit no potential for bioaccumulation (BCF < 150, BCFBAF v3.01 calculation): The metabolism of alcohols has been extensively reviewed in the literature (e.g., see Rizzo et al. 1987, Hargrove et al. 2004). The free alcohols can either be esterified to form wax esters (which are similar to triglycerides) or they can be transformed to fatty acids in a two-step enzymatic process catalyzed by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). The responsible enzymes ADH and ALDH are present in a large number of animals including plants, microorganisms and fish (e.g., Sund and Theorell 1963, Nilsson 1990, Watabiki et al. 1999, Reimers et al. 2004, Lassen et al. 2005).The metabolism of alcohols in fish was extensively 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 sequence similarity of 75% to mammalian ALDH2 enzymes and a similar catalytic activity (also see Nilsson 1988). Metabolism data for adipic acid in aquatic organisms is not available. However, metabolism of adipic acid in rats has been studied by Rusoff et al. (1960). The investigators administered approximately 50 mg 14C-labeled adipic acid to rats by gavage and within 24 hours recovered up to 70 percent of the radioactivity in the breath as carbon dioxide. In addition to adipic acid, Rusoff et al. (1960) also detected five radioactive metabolites including urea, glutamic, lactic,β-ketoadipic, and citric acids in the urine. Due to the presence ofβ-ketoadipic acid in the urine, they suggested that some of the administered adipic acid underwentβ-oxidation toβ-ketoadipic acid which in turn could be further metabolized to succinic acid.



DPHA is not expected to be bioaccumulative. Due to their readily biodegradable nature, extensive degradation of the substance in conventional STPs will take place and only low concentrations are expected to be released into the environment. Once present in the aquatic compartment, further biodegradation will occur and, depending on their log Pow, water solubility and adsorption potential, DPHA 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 DPHA by carboxylesterases into adipic acid and via 2-propylheptanol to 2-propylheptanoic acid is expected. The alcohol is used by these organisms as their main source of energy throughout all the different life stages (early development, growth, reproduction, etc.). Adipic acid does not have the potential to accumulate in adipose tissue due to their low log Pow. The key study with the read across substance reports a BCF value of 27, which clearly indicate that rapid metabolism takes place even when log Pow values are above the trigger value of 4.5. Supporting BCF/BAF values estimated using BCFBAF v3.01 confirm the experimental result (all well below 2000).

The information above provides strong evidence supporting the statement that rapid metabolism and low bioaccumulation potential can be expected for DPHA and its metabolites.



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Felder et al. 1986. Assessment of the safety of dioctyl adipate in freshwater environments. Environ Toxicol Chem 5: 777-784

Heymann E. 1980. Carboxylesterases and amidases. Pp 291-316. In: Jakoby WB (ed) Enzymatic basis of detoxification Vol 2. Biochem Pharmacol Toxicol: A series of monographs, Academic Press

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Linfield WM et al. 1984. Enzymatic fat hydrolysis and synthesis. J Am Oil Chem Soc 61(2): 191-195

Mattson FH and Volpenhein RA. 1972.Hydrolysis of fully esterified alcohols containing from one to eight hydroxyl groups by the lipolytic enzymes of rat pancreatic juice. J Lip Res 13: 325-328

Nilsson GE. 1990. Distribution of aldehyde dehydrogenase and alcohol dehydrogenase in summer-acclimatized crucian carp, Carassius carassius L. J Fish Biol 36(2): 175-179

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 158(4): 479-485

Reimers et al. 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: 38303-38312

Rizzo WB et al. 1987. Fatty alcohol metabolism in cultured human fibroblasts. Evidence for a fatty alcohol cycle. J Biol Chem 262: 17412-17419

Rusoff II, Baldwin RR, Domingues FJ, Monder C, Ohan WJ, Thiessen R Jr. 1960. Intermediary metabolism of adipic acid. Toxicol Appl Pharmacol 2: 316-330

Sund H and Theorell H. 1963. Alcohol dehydrogenases. The Enzymes 7: 25-83

Takahashi T, Tanaka A, Yamaha T. 1981.Elimination, distribution and metabolism of di-(2-ethylhexyl)adipate (DEHA) in rats. Toxicology 22: 223-233

Watabiki T et al. 1999. Intralobular distribution of class I alcohol dehydrogenase and aldehyde dehydrogenase 2 activities in the hamster liver. Alc Clinic Exp Res 23: 52-55

Wheelock CE et al. 2008. Applications of carboxylesterase activity in environmental monitoring and toxicity identification evaluations (TI Es).Rev Environ Contam Toxicol 195: 117-178