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Environmental fate & pathways

Bioaccumulation: aquatic / sediment

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Endpoint:
bioaccumulation in aquatic species: fish
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well documented publication which meets basic scientific principles
Qualifier:
no guideline followed
Principles of method if other than guideline:
The activity of carboxylesterase (CaE), a class of nonspecific serine hydrolases, was evaluated in vitro in tissues and microsomes of rainbow trout. In the assays the formation of 4-nitrophenol from 4-nitrophenyl acetate was measured spectrophotometrically.
GLP compliance:
no
Test organisms (species):
Oncorhynchus mykiss (previous name: Salmo gairdneri)
Details on test organisms:
TEST ORGANISM
- Common name: rainbow trout
- Source: Trouts were obtained as eyed embryos from Mt. Lassen Trout Farms, Mt. Lassen CA, USA
- Age at study initiation: < 1 year
- Length at study initiation (lenght definition, mean, range and SD):
- Weight at study initiation: 1.64 ± 0.07 g wet weight
- Weight at termination (mean and range, SD):
- Method of holding: Trout were held in flow-through aerated raceways at 12 ± 1 °C. The laboratory water was softened Lake Huron water that had been sand-filtered, pH adjusted with CO 2, carbon-filtered, and ultraviolet irradiated. Laboratory water was monitored weekly for pH, alkalinity, conductivity, and hardness; and quarterly for selected inorganics, pesticides, and poly-chlorinated biphenyls. Typical water quality values were pH of 7.5, alkalinity of 43 mg/L, hardness of 70 mg/L (as CaCO3 ), and conductivity of 140 mhos/cm. Fish were killed by a blow to the head and placed immediately on ice before tissue preparation.
Route of exposure:
other: In vitro exposure
Test type:
other: In vitro study
Water / sediment media type:
natural water: freshwater
Remarks on result:
not measured/tested
Remarks:
No BCF was determined. Carboxylesterase activity in fish was monitored.

The results of this study demonstrated that rainbow trout had high esterase activity over a broad range of temperatures, that carboxylesterase (CaE) activity significantly increased between the yolk-sac and juvenile life stages, and that variation between the CaE activity in trout and three other families of freshwater fish was limited.

Endpoint:
bioaccumulation in aquatic species: fish
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Validated QSAR model. The model has no universally accepted definition of model domain, but since the substance is outside the Kow range of the training set (limits of training set: log Kow = 0.31 – 8.70; log Kow of test substance: 11.55), the results should be taken with caution. The definite values may not be fully reliable, but indicate a low bioaccumulation potential, which can be taken into account for further assessments. Therefore, it can be assumed that the bioaccumulation potential of the substance is low.
Justification for type of information:
QSAR prediction: migrated from IUCLID 5.6
Principles of method if other than guideline:
Calculation based on BCFBAF v3.01, Estimation Programs Interface Suite™ for Microsoft® Windows v 4.10. US EPA, United States Environmental Protection Agency, Washington, DC, USA.
GLP compliance:
no
Test organisms (species):
other: Fish
Route of exposure:
aqueous
Test type:
other: calculation
Water / sediment media type:
natural water: freshwater
Details on estimation of bioconcentration:
BASIS FOR CALCULATION OF BCF
- Estimation software: BCFBAF v3.01
- Result based on measured log Pow of: > 6 (BASF, 1998)
- Result based on calculated log Pow of: 7.175 (estimated, KOWWIN v.1.68)
Type:
BAF
Value:
1.1 L/kg
Basis:
whole body w.w.
Remarks on result:
other: Arnot Gobas (including biotransformation rate estimates, upper trophic)
Type:
BCF
Value:
0.91 L/kg
Basis:
whole body w.w.
Remarks on result:
other: Arnot Gobas (including biotransformation rate estimates, upper trophic)
Details on results:
For detailed description on the model and its applicability, see "Any other information on materials and methods incl. tables".

Estimated Log BCF (mid trophic)  = -0.022 (BCF = 0.9505 L/kg wet-wt)

Estimated Log BAF (mid trophic)  = 0.339 (BAF = 2.181 L/kg wet-wt)

Estimated Log BCF (lower trophic) = -0.017 (BCF = 0.9611 L/kg wet-wt)

Estimated Log BAF (lower trophic) = 0.672 (BAF = 4.698 L/kg wet-wt)

Arnot-Gobas BCF & BAF Methods (assuming a biotransformation rate of zero):

Estimated Log BCF (upper trophic) = 0.515 (BCF = 3.273 L/kg wet-wt)

Estimated Log BAF (upper trophic) = 4.083 (BAF = 1.21e+004 L/kg wet-wt)

Biotransformation Rate Constant:

kM (Rate Constant): 0.2782 /day (10 gram fish)

kM (Rate Constant): 0.1565 /day (100 gram fish)

kM (Rate Constant): 0.08798 /day (1 kg fish)

kM (Rate Constant): 0.04947 /day (10 kg fish)

Endpoint:
bioaccumulation in aquatic species: fish
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Validated QSAR model. The model has no universally accepted definition of model domain, but since the substance is outside the Kow range of the training set (limits of training set: log Kow = 0.31 – 8.70; log Kow of test substance: 11.55), the results should be taken with caution. The definite values may not be fully reliable, but indicate a low bioaccumulation potential, which can be taken into account for further assessments. Therefore, it can be assumed that the bioaccumulation potential of the substance is low.
Justification for type of information:
QSAR prediction: migrated from IUCLID 5.6
Principles of method if other than guideline:
Calculation based on BCFBAF v3.01, Estimation Programs Interface Suite™ for Microsoft® Windows v 4.10. US EPA, United States Environmental Protection Agency, Washington, DC, USA.
GLP compliance:
no
Test organisms (species):
other: Fish
Route of exposure:
aqueous
Test type:
other: calculation
Water / sediment media type:
natural water: freshwater
Details on estimation of bioconcentration:
BASIS FOR CALCULATION OF BCF
- Estimation software: BCFBAF v3.01
- Result based on calculated log Pow of: 11.55 (KOWWIN v.1.68)
Type:
BCF
Value:
19.8 L/kg
Basis:
whole body w.w.
Remarks on result:
other: Regression based estimate
Details on results:
For detailed description on the model and its applicability, see "Any other information on materials and methods incl. tables".
Endpoint:
bioaccumulation: aquatic / sediment
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Data from review article.
Qualifier:
no guideline followed
Principles of method if other than guideline:
Review article, describing biotransformation reactions and their effect on toxicity and bioaccumulation of certain chemicals in fish.
GLP compliance:
no
Test organisms (species):
other: not applicable
Route of exposure:
other: not applicable
Test type:
other: not applicable
Remarks on result:
not measured/tested
Remarks:
No BCF was measured; Enzyme activity study

The catalytic activity of the carboxylesterase family leads to a rapid biotransformation/metabolism of xenobiotics which reduces the bioaccumulation or bioconcentration potential. Several in-vivo and in-vitro experiments showed the biotransformation of xenobiotics in fish. The biotransformation reactions have been shown to occur in fish at rates which have siginificant effects on toxicity and residue dynamics of selected chemicals. Inhibition of these reactions can lead to increased toxicity and bioaccumulation factors. Thus, it was shown that the carboxylesterase activity has an influence on the bioaccumulation of xenobiotics.

Description of key information

Diisodecyl azelate is not expected to bioaccumulate in aquatic organisms

Key value for chemical safety assessment

Additional information

No experimental data evaluating the bioaccumulation potential of Diisodecyl azelate (CAS 28472-97-1) are available. The substance exhibits a high log Kow (log Kow = 11.55), suggesting potential to bioaccumulate in biota. However, the information gathered on environmental behaviour and metabolism in combination with QSAR-estimated 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 this substance is likely to show negligible bioaccumulation potential.

Intrinsic properties and fate

Diisodecyl azelate (CAS 28472-97-1) is 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, 2012b).Therefore, after passing through conventional STPs, only low concentrations of these substances are likely to be (if at all) released into the environment.

Diisodecyl azelate (CAS 28472-97-1) exhibits a high log Kow (log Kow = 11.55) and a water solubility < 0.05 mg/L. The Guidance on information requirements and chemical safety assessment, Chapter R.7b (ECHA, 2012b) 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, 2012a) 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 Diisodecyl azelate in fish species is available. Estimated bioconcentration (BCF) and bioaccumulation (BAF) values were calculated for this substance using the BCFBAF v3.01 program (Estimation Programs Interface Suite™ for Microsoft® Windows v 4.10., US EPA), including biotransformation rates (Arnot-Gobas method). Even though the substance is 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 Diisodecyl azelate. The calculated BCF and BAF values are 19.8 L/kg (BCF, regression based estimate) and 0.9 and 1.1 (Arnot-Gobas method, BCF and BAF, respectively). 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 Diisodecyl azelate 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 L/kg. 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 substance will not be bioaccumulative.

Metabolism of Diisodecyl azelate

If aliphatic esters like Diisodecyl azelate are taken up by living organisms, aliphatic esters such as the substance will be initially metabolized via enzymatic hydrolysis to the respective fatty acid and alcohol components as would other dietary fats (e.g., Linfield, 1984). The hydrolysis is catalyzed by carboxylesterases and esterases, with B-esterases located in hepatocytes of mammals being the most important (Heymann, 1980; Anders, 1989). However, carboxylesterase activity has also been reported from a wide variety of tissues in invertebrates and fishes (e.g., Leinweber, 1987; Soldano et al., 1992; Barron et al., 1999; Wheelock et 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 & Melancon, 1980; Lech & Bend, 1980).

Isodecanol and Azelaic acid acid are the expected hydrolysis products from the enzymatic reaction catalyzed by carboxylesterase. The metabolism of fatty alcohols has been intensively 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 & Theorell, 1963; Nilson, 1990; Yoshida et al., 1997; Reimers et al., 2004; Lassen et al., 2005). 

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).

The further metabolism of the fatty acids in general is also well investigated in various organisms, such as plants (e.g., Harwood 1988), fish (e.g., Henderson, 1996; Turchini, 2006) or algae (e.g., Nichols, 1968).The free fatty acids can either be stored as triglycerides or be oxidized via mitochondrial ß-oxidation removing C2-units, in order to store usable energy in form of ATP (Masoro, 1977). Acetyl-CoA, the final product of the ß-oxidation process, can further be mineralized in the tricarboxylic acid cycle via different enzymatically catalyzed processes to carbon dioxide.

Summarizing, Diisodecyl azelate is expected to be rapidly hydrolyzed to Azelaic acid acid and Isodecanol. Both hydrolysis products are supposed to be satisfactory metabolized in aquatic organisms and are not bioaccumulative. Therefore, for Diisodecyl azelate no potential for bioaccumulation is to be expected.

Conclusion

Diisodecyl azelate is not expected to be bioaccumulative. Due to it´s 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 the high log Kow 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 into Isodecanol and Azelaic acid is expected. The supporting BCF/BAF values estimated with the BCFBAF v3.01 program also indicate that this substance will not be bioaccumulative (all well below 2000 L/kg).

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

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