2,2-dimethylpropane-1,3-diyl 2-ethylhexanoate

Bioaccumulation: aquatic / sediment

Link to relevant study record(s)

Reference

Reference 1

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 determinable because of methodological limitations

Details on kinetic parameters:

Not specified

Metabolites:

Not specified

Results with reference substance (positive control):

Not specified

Details on results:

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.

Reported statistics:

Not specified

Validity criteria fulfilled:

not applicable

Reference 2

Endpoint:

bioaccumulation in aquatic species, other

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Validated QSAR model

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: 7.51 (KOWWIN v.1.68)

Type:

BCF

Value:

3.28 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".

Reference 3

Endpoint:

bioaccumulation in aquatic species, other

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Validated QSAR model

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: 7.51 (KOWWIN v.1.68)

Type:

BAF

Value:

16.5 L/kg

Basis:

whole body w.w.

Remarks on result:

other: Arnot Gobas (including biotransformation rate estimates, upper trophic)

Type:

BCF

Value:

15.5 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) = 1.32 (BCF = 20.96 L/kg wet-wt)

Estimated Log BAF (mid trophic) = 1.94 (BAF = 87.64 L/kg wet-wt)

Estimated Log BCF (lower trophic) = 1.36 (BCF = 23.02 L/kg wet-wt)

Estimated Log BAF (lower trophic) = 2.79 (BAF = 630.1 L/kg wet-wt)

 

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

Estimated Log BCF (upper trophic) = 3.80 (BCF = 6336 L/kg wet-wt)

Estimated Log BAF (upper trophic) = 7.16 (BAF = 14460000 L/kg wet-w)

 

Biotransformation Rate Constant:

kM (Rate Constant): 2.537 /day (10 gram fish)

kM (Rate Constant): 1.427 /day (100 gram fish)

kM (Rate Constant): 0.8022 /day (1 kg fish)

kM (Rate Constant): 0.4511 /day (10 kg fish)

Bio Half-Life Normalized to 10 g fish at 15 deg C: 0.273 days

 

Reference 4

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 determinable because of methodological limitations

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.

Reference 5

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: Acceptable, well documented publication which meets basic scientific principles.

Qualifier:

no guideline followed

Principles of method if other than guideline:

In vitro enzyme study with liver microsomal and cytosolic fractions from different fish species recommended as test species in OECD guidelines.

GLP compliance:

no

Test organisms (species):

other: Poecilia reticulata, Cyprinus carpio, Danio rerio, Leuciscus idus, Salmo gairdneri

Details on test organisms:

TEST ORGANISM- Common name: Guppy, common carp, zebra fish, golden orfe, rainbow trout- Source: Guppy, common carp and zebra fish were purchased from Euraquarium, Bologna, Italy. Rainbow trout was kindly supplied by Istituto Ittiogenico, Rome, Italy.- Length at study initiation: see Tab. 1- Weight at study initiation: see Tab. 1- Method of breeding: The guppy stocks were made up of adult females only, whereas all other fish stocks included individuals of both sexes. Fish sizes and rearing conditions were chosen to meet EEC test guidelines as closely as possible. ACCLIMATION- Acclimation period: Fish were acclimatised for at least one week.- Type and amount of food: Fish were fed a semisynthetic diet purchased from Piccioni, Brescia, Italy.- Health during acclimation (any mortality observed): Less than 2% mortality per week was observed in all the stocks used.

Route of exposure:

other: not applicable, in vitro study

Test type:

other: in vitro

Water / sediment media type:

natural water: freshwater

Remarks on result:

not determinable because of methodological limitations

The metabolic efficiency of the liver in the enzymatic hydrolysis of exogenous substrates is dependent on both the substrate type and the fish species. Indeed, the fish studied metabolise much more readily phenyl acetate, the typical substrate of A-esterases, and the phosphate monoester, than the B-esterase substrates. The inter-species differences in activities (referred to unit body weight) vary within a factor of 7 – 17 for esterases (with p-nitrophenyl phosphate, phenyl acetate or ethyl-butyrate as substrate), while reaching a factor of variation of even 60 for acetanilide amidase.

In line with previous evidence on hepatic mono-oxygenase and glutathione S-transferases, guppy is the most active fish species, also with reference to non-specific hydrolases. At variance with results on the other enzyme families, carp also is endowed with the highest levels of hydrolases.

Validity criteria fulfilled:

not applicable

Description of key information

Based on the intrisic properties, fate, metabolism and QSAR data, there is strong evidence to suggest that the test substance 2,2-dimethylpropane-1,3-diyl 2-ethylhexanoate (CAS No. 28510-23-8) is likely to rapidly metabolise in living organisms and has low bioacculumlation.

Additional information

No experimental data evaluating the bioaccumulation potential of 2,2-dimethylpropane-1,3-diyl 2-ethylhexanoate (CAS No. 28510-23-8) is available. The substance exhibits a high log Kow (experimental log Kow > 6, calculated log Kow = 7.5), 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

2,2-dimethylpropane-1,3-diyl 2-ethylhexanoate is not readily biodegradable but showed high overall degradation rates in an enhanced test on ready biodegradation (Desmares-Koopmans, 2012). Therefore, the substance will undergo ultimate degradation in most environments.

2,2-dimethylpropane-1,3-diyl 2-ethylhexanoate (CAS No. 28510-23-8) exhibits a high log Kow and a water solubility < 0.01 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 biodegraded. 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 2,2-dimethylpropane-1,3-diyl 2-ethylhexanoate (CAS No. 28510-23-8) 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). The calculated BCF and BAF values are 3.28 L/kg (BCF, regression based estimate) and 15.5/16.5 L/kg (Arnot-Gobas method, BCF and BAF, respectively). The calculations (especially the low BCF values calculated using the Arnot-Gobas method) reflect the rapid biotransformation assumed for 2,2-dimethylpropane-1,3-diyl 2-ethylhexanoate. 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 2,2-dimethylpropane-1,3-diyl 2-ethylhexanoate is likely to show negligible 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 BCFs provide sufficient reliable evidence which suggests that the substance will not be bioaccumulative.

Metabolism of 2,2-dimethylpropane-1,3-diyl 2-ethylhexanoate

If 2,2-dimethylpropane-1,3-diyl 2-ethylhexanoate is uptaken 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; Suldano 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).

Metabolites

Neopentyl glycol and 2-ethylhexanoic acid are the expected hydrolysis products from the enzymatic reaction catalyzed by carboxylesterase. REACh registration dossiers of 2-Ethylhexanoic acid and Neopentyl glycol are available and can be publicly viewed on the ECHA webpage (http://echa.europa.eu/web/guest/information-on-chemicals/registered-substances). Both substances are not of concern for the environment.

Conclusion

2,2-dimethylpropane-1,3-diyl 2-ethylhexanoate is not expected to be bioaccumulative. Due to its adsorption properties only low concentrations are expected to be released (if at all) into the environment. Once present in the aquatic compartment, due the high log Kow the substance 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 Neopentyl glycol and 2-ethylhexanoic 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 CSR.