Registration Dossier
Registration Dossier
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EC number: 251-646-7 | CAS number: 33703-08-1
Bioaccumulation: aquatic / sediment
Administrative data
Link to relevant study record(s)
- Endpoint:
- bioaccumulation in aquatic species: invertebrate
- Type of information:
- experimental study
- Adequacy of study:
- disregarded due to major methodological deficiencies
- Study period:
- 13 Jul - 3 Aug 1983
- Reliability:
- 3 (not reliable)
- Rationale for reliability incl. deficiencies:
- other: Significant methodological defeciences, i.e. test was perfomed above water solubility
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Study on the accumulation of DEHA and DINA in Daphnia magna
- GLP compliance:
- yes
- Radiolabelling:
- yes
- Vehicle:
- yes
- Details on preparation of test solutions, spiked fish food or sediment:
- PREPARATION AND APPLICATION OF TEST SOLUTION
- Method: The test substance was mixed with acetone. The test substance was added to the test system as a 10000 fold concentrate in acetone to give a constant level of acetone in each treatment and control.
- Chemical name of vehicle (organic solvent, emulsifier or dispersant): acetone
- Concentration of vehicle in test medium (stock solution and final test solution(s) including control(s)): 100 mg/L v/v
- Evidence of undissolved material (e.g. precipitate, surface film, etc): not stated - Test organisms (species):
- Daphnia magna
- Route of exposure:
- aqueous
- Test type:
- flow-through
- Water / sediment media type:
- natural water: freshwater
- Total exposure / uptake duration:
- 21 d
- Test temperature:
- 15 °C
- pH:
- not specified
- Dissolved oxygen:
- not specified
- Details on test conditions:
- TEST SYSTEM
- Renewal rate of test solution (frequency/flow rate): Daphnia were transferred into freshly prepared test solutions every monday, wednesday and friday throughout the test.
- No. of organisms per vessel: 10
- No. of vessels per concentration (replicates): 2
- No. of vessels per control (replicates): 2
- No. of vessels per vehicle control (replicates): 4 - Nominal and measured concentrations:
- Nominal: 3.2, 10, 32 and 100 µg/L
Measured: > 80% of nominal (80.9 - 90.6%) - Reference substance (positive control):
- no
- Type:
- BCF
- Value:
- 815
- Basis:
- not specified
- Remarks on result:
- other: mean BCF, DEHA
- Type:
- BCF
- Value:
- 1 102 - 2 031
- Basis:
- not specified
- Remarks on result:
- other: DINA
- Details on results:
- - Mortality of test organisms: none
- Behavioural abnormalities: none
- Observations on body length and weight: none
- Loss of test substance during test period: Throughout the study, 2 deaths occurred in the solvent control. - Validity criteria fulfilled:
- not applicable
- Executive summary:
This study reports BCF values of 815 for DEHA and 1102 -2031 for DINA in Daphnia magna. Acetone was used as vehicle for the test solution preparation. On the one hand the daphnids might well have filtered and ingested undissolved material, adding to their body burden. Additionally, daphnids were fed microalgae. Again, animals possibly have taken up undissolved test material, which has been attached to the surface of or incorporated by the algae. Most importantly, measurements were based on 14C-activity and not on the substance itself. Thus, radioactivity measured in the daphnids may be due to (i) incorporation of 14C during metabolic processes in the daphnid or via ingestion of algae, which assimilated 14CO2. In summary, the result of the study – if at all valid – is likely to clearly overestimate the bioaccumulation potential of bis(2-ethylhexyl) adipate. Therefore, and since more valid information is available, the study is not taken into account to assess the bioaccumulation potential of bis(2-ethylhexyl) adipate and diisononyl adipate.
- Endpoint:
- bioaccumulation in aquatic species, other
- Type of information:
- experimental study
- Adequacy of study:
- disregarded due to major methodological deficiencies
- Study period:
- 26 Jul - 4 Oct 1983
- Reliability:
- 3 (not reliable)
- Rationale for reliability incl. deficiencies:
- other: Significant methodological defeciences, i.e. test was perfomed above water solubility
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Study on the accumulation and depuration of DEHA and DINA in blue mussels
- GLP compliance:
- yes
- Radiolabelling:
- yes
- Vehicle:
- yes
- Details on preparation of test solutions, spiked fish food or sediment:
- PREPARATION AND APPLICATION OF TEST SOLUTION
- Method: DEHA was prepared as stock solution in 62.5% acetone/water at 1250 times the required test concentrations and this stock solution was mixed into the seawater supply to the test vessels at a nominal 0.4 mL/min.
- Chemical name of vehicle (organic solvent, emulsifier or dispersant): acetone
- Concentration of vehicle in test medium (stock solution and final test solution(s) at different concentrations and in control(s)): not specified
- Evidence of undissolved material (e.g. precipitate, surface film, etc): not reported - Test organisms (species):
- other: Mytilus edulis
- Details on test organisms:
- TEST ORGANISM
- Source: Mussels were collected locally
- Length at study initiation (shell): 24 mm (20 - 27 mm)
- Weight at study initiation: 536 g (318- 798 g)
- Feeding during test
- Food type: unicellular algae (Platymonas suecica)
- Amount: 3000 alga/mL - Route of exposure:
- aqueous
- Test type:
- flow-through
- Water / sediment media type:
- natural water: freshwater
- Total exposure / uptake duration:
- 35 d
- Total depuration duration:
- 35 d
- Test temperature:
- 15 °C
- pH:
- not specified
- Dissolved oxygen:
- not specified
- Details on test conditions:
- TEST SYSTEM
- Renewal rate of test solution (frequency/flow rate): 500 mL/min
- No. of organisms per vessel: 80
- No. of vessels per concentration (replicates): 1
- No. of vessels per control / vehicle control (replicates): 1 - Nominal and measured concentrations:
- Nominal: 5 and 50 µg/L
Measured: 3.9 (1.7 - 5.3) and 35.4 (18.3 - 68.5) µg/L - Reference substance (positive control):
- no
- Type:
- BCF
- Value:
- 20 770
- Basis:
- not specified
- Remarks on result:
- other: DEHA
- Type:
- BCF
- Value:
- 11 000
- Basis:
- not specified
- Remarks on result:
- other: DINA
- Elimination:
- yes
- Parameter:
- DT50
- Depuration time (DT):
- 19.3 d
- Details on results:
- - Mortality of test organisms: none
- Behavioural abnormalities: none
- Observations on body length and weight: none
- Loss of test substance during test period: Throughout the study, 2 deaths occurred in the solvent control. - Executive summary:
This study reports a BCF value of 20770 for DEHA and 11000 for DINA in the common mussel Mytilus edulis. The lower test concentration used in the study was 5 µg/L, which is above the water solubility of the substance (3.2 µg/L). Acetone was used as vehicle for the test solution preparation. On the one hand the mussels might well have filtered and ingested undissolved material, adding to their body burden. Additionally, mussels were fed microalgae. Again, animals possibly have taken up undissolved test material, which has been attached to the surface of or incorporated by the algae. On the other hand the use of the solvent artificially modifies the solubility of the substance in water, which unrealistically enhances exposure.
Finally and most importantly, measurements were based on 14C-activity and not on the substance itself. Thus, radioactivity measured in the mussels may be due to (i) incorporation of 14C during metabolic processes in the mussel (see metabolism of adipic acid) or via ingestion of algae, which assimilated 14CO2. In summary, the result of the study – if at all valid – is likely to clearly overestimate the bioaccumulation potential of bis(2-ethylhexyl) adipate. Therefore, and since more valid information is available, the study is not taken into account to assess the bioaccumulation potential of bis(2-ethylhexyl) adipate and diisononyl adipate.
- Endpoint:
- bioaccumulation in aquatic species: fish
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Acceptable, well documented and peer reviewed publication which meets basic scientific principles
- Justification for type of information:
- REPORTING FORMAT FOR THE ANALOGUE APPROACH
See explainations in the endpoint study summary and the analogue justification document attached in chapter 12. - Reason / purpose for cross-reference:
- read-across source
- Key result
- Type:
- BCF
- Value:
- 27
- Remarks on result:
- other: Conc.in environment / dose:0.25 mg/L
- Endpoint:
- bioaccumulation in aquatic species, other
- Type of information:
- (Q)SAR
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
- Justification for type of information:
- 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.
For details see QMRF and QPRF inserted in "Overall remarks" and executive summary", respectively. - 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: 9.24 (KOWWIN v1.68) - Key result
- Type:
- BCF
- Value:
- 268 L/kg
- Basis:
- whole body w.w.
- Remarks on result:
- other: The substance is within the applicability domain of the BCFBAF submodel: Bioconcentration factor (BCF; Meylan et al., 1997/1999).
- Type:
- BCF
- Value:
- 1.17 L/kg
- Basis:
- whole body w.w.
- Calculation basis:
- steady state
- Remarks on result:
- other: Upper trophic, incl. biotransformation estimates; Arnot & Gobas BAF and steady-state BCF Arnot & Gobas, 2003).
- Type:
- BCF
- Value:
- 438.5 L/kg
- Basis:
- whole body w.w.
- Calculation basis:
- steady state
- Remarks on result:
- other: Upper trophic, incl. biotransformation rate of zero; Arnot & Gobas BAF and steady-state BCF Arnot & Gobas, 2003).
- Type:
- BAF
- Value:
- 1.21 L/kg
- Basis:
- whole body w.w.
- Remarks on result:
- other: Upper trophic, incl. biotransformation estimates; Arnot & Gobas BAF and steady-state BCF Arnot & Gobas, 2003).
- Type:
- BAF
- Value:
- 2 175 000 L/kg
- Basis:
- whole body w.w.
- Remarks on result:
- other: Upper trophic, incl. biotransformation rate of zero; Arnot & Gobas BAF and steady-state BCF Arnot & Gobas, 2003).
- Details on kinetic parameters:
- Biotransformation half-life (days): 0.6355
Biotransformation rate (kM, normalised to 10 g fish at 15 °C): -
The substance is within the applicability domain of the BCFBAF submodel: Biotransformation rate in fish (kM; Arnot et al., 2008a/b). - Executive summary:
QPRF: BCFBAF v3.01
1.
Substance
See “Test material identity”
2.
General information
2.1
Date of QPRF
See “Data Source (Reference)”
2.2
QPRF author and contact details
See “Data Source (Reference)”
3.
Prediction
3.1
Endpoint
(OECD Principle 1)Endpoint
Bioaccumulation (aquatic)
Dependent variable
- Bioconcentration factor (BCF)
- Bioaccumulation factor (BAF; 15 °C)
- Biotransformation rate (kM) and half-life
3.2
Algorithm
(OECD Principle 2)Model or submodel name
BCFBAF
Submodels:
1) Bioconcentration factor (BCF; Meylan et al., 1997/1999)
2) Biotransformation rate in fish (kM; Arnot et al., 2008a/b)
3) Arnot & Gobas BAF and steady-state BCF Arnot & Gobas, 2003)
Model version
v. 3.01
Reference to QMRF
Estimation of Bioconcentration, bioaccumulation and biotransformation in fish using BCFBAF v3.01 (EPI Suite v4.11)
Predicted value (model result)
See “Results and discussion”
Input for prediction
Chemical structure via CAS number or SMILES; log Kow (optional)
Descriptor values
- SMILES: structure of the compound as SMILES notation
- log Kow
- Molecular weight
3.3
Applicability domain
(OECD principle 3)Domains:
1) Bioconcentration factor (BCF; Meylan et al., 1997/1999)
a) Ionic/non-Ionic
The substance is non-ionic.
b) Molecular weight (range of test data set):
- Ionic: 68.08 to 991.80
- Non-ionic: 68.08 to 959.17
(On-Line BCFBAF Help File, Ch. 7.1.3 Estimation Domain and Appendix G)
The substance is within range (398.63 g/mol).
c) log Kow (range of test data set):
- Ionic: -6.50 to 11.26
- Non-ionic: -1.37 to 11.26
(On-Line BCFBAF Help File, Ch. 7.1.3 Estimation Domain and Appendix G)
The substance is within range (9.24).
d) Maximum number of instances of correction factor in any of the training set compounds (On-Line BCFBAF Help File, Appendix E)
Not exceeded.
2) Biotransformation rate in fish (kM; Arnot et al., 2008a/b)
a) The substance does not appreciably ionize at physiological pH.
(On-Line BCFBAF Help File, Ch. 7.2.3)
fulfilled
b) Molecular weight (range of test data set): 68.08 to 959.17
(On-Line BCFBAF Help File, Ch. 7.2.3)
The substance is within range (398.63 g/mol).
c) The molecular weight is ≤ 600 g/mol.
(On-Line BCFBAF Help File, Ch. 7.2.3)
fulfilled
d) Log Kow: 0.31 to 8.70
(On-Line BCFBAF Help File, Ch. 7.2.3)
The substance is not within range (9.24).
e) The substance is no metal or organometal, pigment or dye, or a perfluorinated substance.
(On-Line BCFBAF Help File, Ch. 7.2.3)
fulfilled
f) Maximum number of instances of biotransformation fragments in any of the training set compounds (On-Line BCFBAF Help File, Appendix F)
Not exceeded.
3) Arnot & Gobas BAF and steady-state BCF Arnot & Gobas, 2003)
a) Log Kow ≤ 9
(On-Line BCFBAF Help File, Ch. 7.3.1)
not fulfilled
b) The substance does not appreciably ionize.
(On-Line BCFBAF Help File, Ch. 7.3.1)
fulfilled
c) The substance is no pigment, dye, or perfluorinated substance.
(On-Line BCFBAF Help File, Ch. 7.3.1)
fulfilled
3.4
The uncertainty of the prediction
(OECD principle 4)1. Bioconcentration factor (BCF; Meylan et al., 1997/1999)
Statistical accuracy of the training data set (non-ionic plus ionic data):
- Correlation coefficient (r2) = 0.833
- Standard deviation = 0.502 log units
- Absolute mean error = 0.382 log units
2. Biotransformation Rate in Fish (kM)
Statistical accuracy (training set):
- Correlation coefficient (r2) = 0.821
- Correlation coefficient (Q2) = 0.753
- Standard deviation = 0.494 log units
- Absolute mean error = 0.383 log units
3. Arnot-Gobas BAF/BCF model
No information on the statistical accuracy given in the documentation.
3.5
The chemical mechanisms according to the model underpinning the predicted result
(OECD principle 5)1. The BCF model is mainly based on the relationship between bioconcentration and hydrophobicity. The model also takes into account the chemical structure and the ionic/non-ionic character of the substance.
2. Bioaccumulation is the net result of relative rates of chemical inputs to an organism from multimedia exposures (e.g., air, food, and water) and chemical outputs (or elimination) from the organism.
3. The model includes mechanistic processes for bioconcentration and bioaccumulation such as chemical uptake from the water at the gill surface (BCFs and BAFs) and the diet (BAFs only), and chemical elimination at the gill surface, fecal egestion, growth dilution and metabolic biotransformation (Arnot and Gobas 2003). Other processes included in the calculations are bioavailability in the water column (only the freely dissolved fraction can bioconcentrate) and absorption efficiencies at the gill and in the gastrointestinal tract.
References
- Arnot JA, Gobas FAPC. 2003. A generic QSAR for assessing the bioaccumulation potential of organic chemicals in aquatic food webs. QSAR and Combinatorial Science 22: 337-345.
- Arnot JA, Mackay D, Parkerton TF, Bonnell M. 2008a. A database of fish biotransformation rates for organic chemicals. Environmental Toxicology and Chemistry 27(11), 2263-2270.
- Arnot JA, Mackay D, Bonnell M. 2008b.Estimating metabolic biotransformation rates in fish from laboratory data. Environmental Toxicology and Chemistry 27: 341-351.
- Meylan, W.M., Howard, P.H, Aronson, D., Printup, H. and S. Gouchie. 1997. "Improved Method for Estimating Bioconcentration Factor (BCF) from Octanol-Water Partition Coefficient", SRC TR-97-006 (2nd Update), July 22, 1997; prepared for: Robert S. Boethling, EPA-OPPT, Washington, DC; Contract No. 68-D5-0012; prepared by: ; Syracuse Research Corp., Environmental Science Center, 6225 Running Ridge Road, North Syracuse, NY 13212.
- Meylan, WM, Howard, PH, Boethling, RS et al. 1999. Improved Method for Estimating Bioconcentration / Bioaccumulation Factor from Octanol/Water Partition Coefficient. Environ. Toxicol. Chem. 18(4): 664-672 (1999).
- US EPA (2012). On-Line BCFBAF Help File.
Identified Correction Factors (Appendix E), Biotransformation Fragments and Coefficient values (Appendix F)
Appendix E: BCF Non-Ionic Correction Factors Used by BCFBAF The Training Set used to derive the BCF Correction Factors listed below contained a total of 431 compounds (see Appendix G for the compound list). The number of compounds in the training set with logKow values of 1.0 to 7.0 total 396 compounds ... 35 training set compounds have a logKow value greater than 7.0 ... Compounds with logKow less than 1.0 were not used to derive correction factors. Correction Factor BCFBAF No. compounds containing factor in training set Maximum number of each fragment in any individual compound No. of instances of each fragment for the current substance Appendix F: kM Biotransformation Fragments & Coefficient Values . The Training Set used to derive the Coefficient Values listed below contained a total of 421 compounds (see Appendix I for the compound list). . Fragment Description Coefficient value No. compounds containing fragment in total training set Maximum number of each fragment in any individual compound No. of instances of each fragment for the current substance Linear C4 terminal chain [CCC-CH3] 0,03412373 43 3 2 Ester [-C(=O)-O-C] -0,76052851 15 2 2 Methyl [-CH3] 0,24510529 170 12 2 -CH2- [linear] 0,02418707 109 28 20 Assessment of applicability domain based on molecular weight and log Kow . 1. Bioconcentration Factor (BCF; Meylan et al., 1997/1999) . Training set: Molecular weights Ionic Non-ionic . Minimum 68,08 68,08 . Maximum 991,80 959,17 . Average 244,00 244,00 . Assessment of molecular weight Molecular weight within range of training set. . . Training set: Log Kow Ionic Non-ionic . Minimum -6,50 -1,37 . Maximum 11,26 11,26 . Assessment of log Kow Log Kow within range of training set. . . 2. Biotransformation Rate in Fish (kM; Arnot et al., 2008a/b) . Training set: Molecular weights . Minimum 68,08 . Maximum 959,17 . Average 259,75 . Assessment of molecular weight Molecular weight within range of training set. . . Training set: Log Kow . Minimum 0,31 . Maximum 8,70 . Assessment of log Kow Log Kow outside of range of training set. Therefore, the estimate may be less accurate. . . - Endpoint:
- bioaccumulation in aquatic species: fish
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- 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
- Endpoint:
- bioaccumulation: aquatic / sediment
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Data from review article/book chapter.
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- no data
- GLP compliance:
- no
- Test organisms (species):
- other: not applicable
- Route of exposure:
- other: not applicable
- Endpoint:
- bioaccumulation: aquatic / sediment
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- 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
- Endpoint:
- bioaccumulation: aquatic / sediment
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- The study was conducted to examine the effects and fate of a number of chemicals, including hydrocarbons and chlorinated hydrocarbons. The interactions between these chemicals in fish were studied using several approaches: examination of the uptake, metabolism and elimination of selected chemicals by fish; assessment of the effects of selected inducing agents on hepatic xenobiotic metabolizing enzymes (assayed in vitro); and studies of the effects of inducing agents on the metabolism and disposition of other chemicals in vitro.
- GLP compliance:
- no
- Test organisms (species):
- other: Salmo gairdneri, Lepomis macrochirus, Cyprinus carpio and Archosargus probatocephalus
- Route of exposure:
- other: intraperitoneal injection
- Endpoint:
- bioaccumulation in aquatic species: fish
- Type of information:
- (Q)SAR
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
- Justification for type of information:
- For details of QSAR validity see QMRF and QPRF attached.
- Principles of method if other than guideline:
- Calculation using Catalogic v.5.11.19
- GLP compliance:
- no
- Key result
- Type:
- BCF
- Value:
- 7.27
- Remarks on result:
- other: Considering the mitigating factors size, metabolism and water solubility
- Details on results:
- OASIS predicts the logBCF (corrected) of diisononyl adipate to be 0.862 ± 0.077
- Conclusions:
- The substance is not expected to exhibit a significant bioaccumulation potential. The low water solubility, its molecular size and metabolism decrease the bioaccumulation potential.
- Endpoint:
- bioaccumulation in aquatic species, other
- Type of information:
- (Q)SAR
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
- Justification for type of information:
- 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.
For details see QMRF and QPRF inserted in "Overall remarks" and executive summary", respectively. - 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: 8.12 (KOWWIN v1.68) - Type:
- BCF
- Value:
- 957.1 L/kg
- Basis:
- whole body w.w.
- Remarks on result:
- other: The substance is within the applicability domain of the BCFBAF submodel: Bioconcentration factor (BCF; Meylan et al., 1997/1999).
- Type:
- BCF
- Value:
- 5.47 L/kg
- Basis:
- whole body w.w.
- Calculation basis:
- steady state
- Remarks on result:
- other: Upper trophic, incl. biotransformation estimates; The substance is within the applicability domain of the BCFBAF submodel: Arnot & Gobas BAF and steady-state BCF Arnot & Gobas, 2003).
- Type:
- BCF
- Value:
- 2 999 L/kg
- Basis:
- whole body w.w.
- Calculation basis:
- steady state
- Remarks on result:
- other: Upper trophic, incl. biotransformation rate of zero; The substance is within the applicability domain of the BCFBAF submodel: Arnot & Gobas BAF and steady-state BCF Arnot & Gobas, 2003).
- Type:
- BAF
- Value:
- 6.18 L/kg
- Basis:
- whole body w.w.
- Remarks on result:
- other: Upper trophic, incl. biotransformation estimates; The substance is within the applicability domain of the BCFBAF submodel: Arnot & Gobas BAF and steady-state BCF Arnot & Gobas, 2003).
- Type:
- BAF
- Value:
- 11 670 000 L/kg
- Basis:
- whole body w.w.
- Remarks on result:
- other: Upper trophic, incl. biotransformation rate of zero; The substance is within the applicability domain of the BCFBAF submodel: Arnot & Gobas BAF and steady-state BCF Arnot & Gobas, 2003).
- Details on kinetic parameters:
- Biotransformation half-life (days): 0.3095
Biotransformation rate (kM, normalised to 10 g fish at 15 °C): -
The substance is within the applicability domain of the BCFBAF submodel: Biotransformation rate in fish (kM; Arnot et al., 2008a/b). - Executive summary:
QPRF: BCFBAF v3.01
1.
Substance
See “Test material identity”
2.
General information
2.1
Date of QPRF
See “Data Source (Reference)”
2.2
QPRF author and contact details
See “Data Source (Reference)”
3.
Prediction
3.1
Endpoint
(OECD Principle 1)Endpoint
Bioaccumulation (aquatic)
Dependent variable
- Bioconcentration factor (BCF)
- Bioaccumulation factor (BAF; 15 °C)
- Biotransformation rate (kM) and half-life
3.2
Algorithm
(OECD Principle 2)Model or submodel name
BCFBAF
Submodels:
1) Bioconcentration factor (BCF; Meylan et al., 1997/1999)
2) Biotransformation rate in fish (kM; Arnot et al., 2008a/b)
3) Arnot & Gobas BAF and steady-state BCF Arnot & Gobas, 2003)
Model version
v. 3.01
Reference to QMRF
Estimation of Bioconcentration, bioaccumulation and biotransformation in fish using BCFBAF v3.01 (EPI Suite v4.11)
Predicted value (model result)
See “Results and discussion”
Input for prediction
Chemical structure via CAS number or SMILES; log Kow (optional)
Descriptor values
- SMILES: structure of the compound as SMILES notation
- log Kow
- Molecular weight
3.3
Applicability domain
(OECD principle 3)Domains:
1) Bioconcentration factor (BCF; Meylan et al., 1997/1999)
a) Ionic/non-Ionic
The substance is non-ionic.
b) Molecular weight (range of test data set):
- Ionic: 68.08 to 991.80
- Non-ionic: 68.08 to 959.17
(On-Line BCFBAF Help File, Ch. 7.1.3 Estimation Domain and Appendix G)
The substance is within range (370.58 g/mol).
c) log Kow (range of test data set):
- Ionic: -6.50 to 11.26
- Non-ionic: -1.37 to 11.26
(On-Line BCFBAF Help File, Ch. 7.1.3 Estimation Domain and Appendix G)
The substance is within range (8.94).
d) Maximum number of instances of correction factor in any of the training set compounds (On-Line BCFBAF Help File, Appendix E)
Not exceeded.
2) Biotransformation rate in fish (kM; Arnot et al., 2008a/b)
a) The substance does not appreciably ionize at physiological pH.
(On-Line BCFBAF Help File, Ch. 7.2.3)
fulfilled
b) Molecular weight (range of test data set): 68.08 to 959.17
(On-Line BCFBAF Help File, Ch. 7.2.3)
The substance is within range (370.58 g/mol).
c) The molecular weight is ≤ 600 g/mol.
(On-Line BCFBAF Help File, Ch. 7.2.3)
fulfilled
d) Log Kow: 0.31 to 8.70
(On-Line BCFBAF Help File, Ch. 7.2.3)
The substance is not within range (8.94).
e) The substance is no metal or organometal, pigment or dye, or a perfluorinated substance.
(On-Line BCFBAF Help File, Ch. 7.2.3)
fulfilled
f) Maximum number of instances of biotransformation fragments in any of the training set compounds (On-Line BCFBAF Help File, Appendix F)
Not exceeded.
3) Arnot & Gobas BAF and steady-state BCF Arnot & Gobas, 2003)
a) Log Kow ≤ 9
(On-Line BCFBAF Help File, Ch. 7.3.1)
fulfilled
b) The substance does not appreciably ionize.
(On-Line BCFBAF Help File, Ch. 7.3.1)
fulfilled
c) The substance is no pigment, dye, or perfluorinated substance.
(On-Line BCFBAF Help File, Ch. 7.3.1)
fulfilled
3.4
The uncertainty of the prediction
(OECD principle 4)1. Bioconcentration factor (BCF; Meylan et al., 1997/1999)
Statistical accuracy of the training data set (non-ionic plus ionic data):
- Correlation coefficient (r2) = 0.833
- Standard deviation = 0.502 log units
- Absolute mean error = 0.382 log units
2. Biotransformation Rate in Fish (kM)
Statistical accuracy (training set):
- Correlation coefficient (r2) = 0.821
- Correlation coefficient (Q2) = 0.753
- Standard deviation = 0.494 log units
- Absolute mean error = 0.383 log units
3. Arnot-Gobas BAF/BCF model
No information on the statistical accuracy given in the documentation.
3.5
The chemical mechanisms according to the model underpinning the predicted result
(OECD principle 5)1. The BCF model is mainly based on the relationship between bioconcentration and hydrophobicity. The model also takes into account the chemical structure and the ionic/non-ionic character of the substance.
2. Bioaccumulation is the net result of relative rates of chemical inputs to an organism from multimedia exposures (e.g., air, food, and water) and chemical outputs (or elimination) from the organism.
3. The model includes mechanistic processes for bioconcentration and bioaccumulation such as chemical uptake from the water at the gill surface (BCFs and BAFs) and the diet (BAFs only), and chemical elimination at the gill surface, fecal egestion, growth dilution and metabolic biotransformation (Arnot and Gobas 2003). Other processes included in the calculations are bioavailability in the water column (only the freely dissolved fraction can bioconcentrate) and absorption efficiencies at the gill and in the gastrointestinal tract.
References
- Arnot JA, Gobas FAPC. 2003. A generic QSAR for assessing the bioaccumulation potential of organic chemicals in aquatic food webs. QSAR and Combinatorial Science 22: 337-345.
- Arnot JA, Mackay D, Parkerton TF, Bonnell M. 2008a. A database of fish biotransformation rates for organic chemicals. Environmental Toxicology and Chemistry 27(11), 2263-2270.
- Arnot JA, Mackay D, Bonnell M. 2008b.Estimating metabolic biotransformation rates in fish from laboratory data. Environmental Toxicology and Chemistry 27: 341-351.
- Meylan, W.M., Howard, P.H, Aronson, D., Printup, H. and S. Gouchie. 1997. "Improved Method for Estimating Bioconcentration Factor (BCF) from Octanol-Water Partition Coefficient", SRC TR-97-006 (2nd Update), July 22, 1997; prepared for: Robert S. Boethling, EPA-OPPT, Washington, DC; Contract No. 68-D5-0012; prepared by: ; Syracuse Research Corp., Environmental Science Center, 6225 Running Ridge Road, North Syracuse, NY 13212.
- Meylan, WM, Howard, PH, Boethling, RS et al. 1999. Improved Method for Estimating Bioconcentration / Bioaccumulation Factor from Octanol/Water Partition Coefficient. Environ. Toxicol. Chem. 18(4): 664-672 (1999).
- US EPA (2012). On-Line BCFBAF Help File.
Identified Correction Factors (Appendix E), Biotransformation Fragments and Coefficient values (Appendix F)
The Training Set used to derive the Coefficient Values listed below contained a total of 421 compounds (see Appendix I for the compound list).
.
Fragment Description
Coefficient value
No. compounds containing fragment in total training set
Maximum number of each fragment in any individual compound
No. of instances of each fragment for the current substance
Linear C4 terminal chain [CCC-CH3]
0,03412373
43
3
2
Ester [-C(=O)-O-C]
-0,76052851
15
2
2
Methyl [-CH3]
0,24510529
170
12
4
-CH2- [linear]
0,02418707
109
28
14
-CH- [linear]
-0.19123158
50
2
2
Assessment of Applicability Domain Based on Molecular Weight and log Kow
1. Bioconcentration Factor (BCF; Meylan et al., 1997/1999)
Training set: Molecular weights
Ionic
Non-ionic
Minimum
68,08
68,08
Maximum
991,80
959,17
Average
244,00
244,00
Assessment of molecular weight
Molecular weight within range of training set.
Training set: Log Kow
Ionic
Non-ionic
Minimum
-6,50
-1,37
Maximum
11,26
11,26
Assessment of log Kow
Log Kow within range of training set.
2. Biotransformation Rate in Fish (kM; Arnot et al., 2008a/b)
Training set: Molecular weights
Minimum
68,08
Maximum
959,17
Average
259,75
Assessment of molecular weight
Molecular weight within range of training set.
Training set: Log Kow
Minimum
0,31
Maximum
8,70
Assessment of log Kow
Log Kow outside of range of training set. Therefore, the estimate may be less accurate.
- Endpoint:
- bioaccumulation: aquatic / sediment
- Type of information:
- (Q)SAR
- Adequacy of study:
- supporting study
- 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 using Catalogic v.5.11.9TB, BCF base-line model v.02.05 (new ionization term)
- GLP compliance:
- no
- Details on estimation of bioconcentration:
- BASIS FOR CALCULATION OF BCF
- Estimation software: OASIS Catalogic v5.11.9TB [BCF base line model v.02.05 (new ionization term]
INPUT DATA USED BY THE MODEL:
- log Kow: 16.76 (KOWWIN v1.68 estimate)
- Water solubility: 2.457E-012 mg/L (WSKOW v1.42 estimate) - Type:
- BCF
- Value:
- 24.55
- Remarks on result:
- other: Without considering the mitigating factors size, metabolism and water solubility
- Type:
- other: log BCF
- Value:
- 1.39
- Remarks on result:
- other: ± 0.17; without considering the mitigating factors size, metabolism and water solubility
- Type:
- BCF
- Value:
- 7.08
- Remarks on result:
- other: Considering the mitigating factors size, metabolism and water solubility
- Type:
- other: log BCF
- Value:
- 0.85
- Remarks on result:
- other: ± 0.11; Considering the mitigating factors size, metabolism and water solubility
- Conclusions:
- The substance is not expected to exhibit a significant bioaccumulation potential. The low water solubility, its molecular size and metabolism decrease the bioaccumulation potential.
- Endpoint:
- bioaccumulation in aquatic species, other
- Type of information:
- (Q)SAR
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Validated QSAR model. Calculation for degradation product of DINA and DEHA.
- Justification for type of information:
- 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.
For details see QMRF and QPRF inserted in "Overall remarks" and executive summary", respectively. - 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: 0.23 (KOWWIN v1.68) - Type:
- BCF
- Value:
- 3.162 L/kg
- Basis:
- whole body w.w.
- Remarks on result:
- other: The substance is within the applicability domain of the BCFBAF submodel: Bioconcentration factor (BCF; Meylan et al., 1997/1999).
- Type:
- BCF
- Value:
- 0.99 L/kg
- Basis:
- whole body w.w.
- Calculation basis:
- steady state
- Remarks on result:
- other: Upper trophic, incl. biotransformation estimates; The substance is within the applicability domain of the BCFBAF submodel: Arnot & Gobas BAF and steady-state BCF Arnot & Gobas, 2003).
- Type:
- BCF
- Value:
- 1.022 L/kg
- Basis:
- whole body w.w.
- Calculation basis:
- steady state
- Remarks on result:
- other: Upper trophic, incl. biotransformation rate of zero; The substance is within the applicability domain of the BCFBAF submodel: Arnot & Gobas BAF and steady-state BCF Arnot & Gobas, 2003).
- Type:
- BAF
- Value:
- 0.99 L/kg
- Basis:
- whole body w.w.
- Remarks on result:
- other: Upper trophic, incl. biotransformation estimates; The substance is within the applicability domain of the BCFBAF submodel: Arnot & Gobas BAF and steady-state BCF Arnot & Gobas, 2003).
- Type:
- BAF
- Value:
- 1.023 L/kg
- Basis:
- whole body w.w.
- Remarks on result:
- other: Upper trophic, incl. biotransformation rate of zero; The substance is within the applicability domain of the BCFBAF submodel: Arnot & Gobas BAF and steady-state BCF Arnot & Gobas, 2003).
- Details on kinetic parameters:
- Biotransformation half-life (days): 0.0933
Biotransformation rate (kM, normalised to 10 g fish at 15 °C): -
The substance is within the applicability domain of the BCFBAF submodel: Biotransformation rate in fish (kM; Arnot et al., 2008a/b). - Executive summary:
QPRF: BCFBAF v3.01
1.
Substance
See “Test material identity”
2.
General information
2.1
Date of QPRF
See “Data Source (Reference)”
2.2
QPRF author and contact details
See “Data Source (Reference)”
3.
Prediction
3.1
Endpoint
(OECD Principle 1)Endpoint
Bioaccumulation (aquatic)
Dependent variable
- Bioconcentration factor (BCF)
- Bioaccumulation factor (BAF; 15 °C)
- Biotransformation rate (kM) and half-life
3.2
Algorithm
(OECD Principle 2)Model or submodel name
BCFBAF
Submodels:
1) Bioconcentration factor (BCF; Meylan et al., 1997/1999)
2) Biotransformation rate in fish (kM; Arnot et al., 2008a/b)
3) Arnot & Gobas BAF and steady-state BCF Arnot & Gobas, 2003)
Model version
v. 3.01
Reference to QMRF
Estimation of Bioconcentration, bioaccumulation and biotransformation in fish using BCFBAF v3.01 (EPI Suite v4.11)
Predicted value (model result)
See “Results and discussion”
Input for prediction
Chemical structure via CAS number or SMILES; log Kow (optional)
Descriptor values
- SMILES: structure of the compound as SMILES notation
- log Kow
- Molecular weight
3.3
Applicability domain
(OECD principle 3)Domains:
1) Bioconcentration factor (BCF; Meylan et al., 1997/1999)
a) Ionic/non-Ionic
The substance is non-ionic.
b) Molecular weight (range of test data set):
- Ionic: 68.08 to 991.80
- Non-ionic: 68.08 to 959.17
(On-Line BCFBAF Help File, Ch. 7.1.3 Estimation Domain and Appendix G)
The substance is within range (146.14 g/mol).
c) log Kow (range of test data set):
- Ionic: -6.50 to 11.26
- Non-ionic: -1.37 to 11.26
(On-Line BCFBAF Help File, Ch. 7.1.3 Estimation Domain and Appendix G)
The substance is within range (0.23).
d) Maximum number of instances of correction factor in any of the training set compounds (On-Line BCFBAF Help File, Appendix E)
Not exceeded.
2) Biotransformation rate in fish (kM; Arnot et al., 2008a/b)
a) The substance does not appreciably ionize at physiological pH.
(On-Line BCFBAF Help File, Ch. 7.2.3)
fulfilled
b) Molecular weight (range of test data set): 68.08 to 959.17
(On-Line BCFBAF Help File, Ch. 7.2.3)
The substance is within range (370.58 g/mol).
c) The molecular weight is ≤ 600 g/mol.
(On-Line BCFBAF Help File, Ch. 7.2.3)
fulfilled
d) Log Kow: 0.31 to 8.70
(On-Line BCFBAF Help File, Ch. 7.2.3)
The substance is not within range (0.23).
e) The substance is no metal or organometal, pigment or dye, or a perfluorinated substance.
(On-Line BCFBAF Help File, Ch. 7.2.3)
fulfilled
f) Maximum number of instances of biotransformation fragments in any of the training set compounds (On-Line BCFBAF Help File, Appendix F)
Not exceeded.
3) Arnot & Gobas BAF and steady-state BCF Arnot & Gobas, 2003)
a) Log Kow ≤ 9
(On-Line BCFBAF Help File, Ch. 7.3.1)
fulfilled
b) The substance does not appreciably ionize.
(On-Line BCFBAF Help File, Ch. 7.3.1)
fulfilled
c) The substance is no pigment, dye, or perfluorinated substance.
(On-Line BCFBAF Help File, Ch. 7.3.1)
fulfilled
3.4
The uncertainty of the prediction
(OECD principle 4)1. Bioconcentration factor (BCF; Meylan et al., 1997/1999)
Statistical accuracy of the training data set (non-ionic plus ionic data):
- Correlation coefficient (r2) = 0.833
- Standard deviation = 0.502 log units
- Absolute mean error = 0.382 log units
2. Biotransformation Rate in Fish (kM)
Statistical accuracy (training set):
- Correlation coefficient (r2) = 0.821
- Correlation coefficient (Q2) = 0.753
- Standard deviation = 0.494 log units
- Absolute mean error = 0.383 log units
3. Arnot-Gobas BAF/BCF model
No information on the statistical accuracy given in the documentation.
3.5
The chemical mechanisms according to the model underpinning the predicted result
(OECD principle 5)1. The BCF model is mainly based on the relationship between bioconcentration and hydrophobicity. The model also takes into account the chemical structure and the ionic/non-ionic character of the substance.
2. Bioaccumulation is the net result of relative rates of chemical inputs to an organism from multimedia exposures (e.g., air, food, and water) and chemical outputs (or elimination) from the organism.
3. The model includes mechanistic processes for bioconcentration and bioaccumulation such as chemical uptake from the water at the gill surface (BCFs and BAFs) and the diet (BAFs only), and chemical elimination at the gill surface, fecal egestion, growth dilution and metabolic biotransformation (Arnot and Gobas 2003). Other processes included in the calculations are bioavailability in the water column (only the freely dissolved fraction can bioconcentrate) and absorption efficiencies at the gill and in the gastrointestinal tract.
References
- Arnot JA, Gobas FAPC. 2003. A generic QSAR for assessing the bioaccumulation potential of organic chemicals in aquatic food webs. QSAR and Combinatorial Science 22: 337-345.
- Arnot JA, Mackay D, Parkerton TF, Bonnell M. 2008a. A database of fish biotransformation rates for organic chemicals. Environmental Toxicology and Chemistry 27(11), 2263-2270.
- Arnot JA, Mackay D, Bonnell M. 2008b.Estimating metabolic biotransformation rates in fish from laboratory data. Environmental Toxicology and Chemistry 27: 341-351.
- Meylan, W.M., Howard, P.H, Aronson, D., Printup, H. and S. Gouchie. 1997. "Improved Method for Estimating Bioconcentration Factor (BCF) from Octanol-Water Partition Coefficient", SRC TR-97-006 (2nd Update), July 22, 1997; prepared for: Robert S. Boethling, EPA-OPPT, Washington, DC; Contract No. 68-D5-0012; prepared by: ; Syracuse Research Corp., Environmental Science Center, 6225 Running Ridge Road, North Syracuse, NY 13212.
- Meylan, WM, Howard, PH, Boethling, RS et al. 1999. Improved Method for Estimating Bioconcentration / Bioaccumulation Factor from Octanol/Water Partition Coefficient. Environ. Toxicol. Chem. 18(4): 664-672 (1999).
- US EPA (2012). On-Line BCFBAF Help File.
Identified Correction Factors (Appendix E), Biotransformation Fragments and Coefficient values (Appendix F)
The Training Set used to derive the Coefficient Values listed below contained a total of 421 compounds (see Appendix I for the compound list).
.
Fragment Description
Coefficient value
No. compounds containing fragment in total training set
Maximum number of each fragment in any individual compound
No. of instances of each fragment for the current substance
Aliphatic acid [-C(=O)-OH]
0,38030117
1
2
2
-CH2- [linear]
0,02418707
109
28
4
Assessment of Applicability Domain Based on Molecular Weight and log Kow
1. Bioconcentration Factor (BCF; Meylan et al., 1997/1999)
Training set: Molecular weights
Ionic
Non-ionic
Minimum
68,08
68,08
Maximum
991,80
959,17
Average
244,00
244,00
Assessment of molecular weight
Molecular weight within range of training set.
Training set: Log Kow
Ionic
Non-ionic
Minimum
-6,50
-1,37
Maximum
11,26
11,26
Assessment of log Kow
Log Kow within range of training set.
2. Biotransformation Rate in Fish (kM; Arnot et al., 2008a/b)
Training set: Molecular weights
Minimum
68,08
Maximum
959,17
Average
259,75
Assessment of molecular weight
Molecular weight within range of training set.
Training set: Log Kow
Minimum
0,31
Maximum
8,70
Assessment of log Kow
Log Kow outside of range of training set. Therefore, the estimate may be less accurate.
- Endpoint:
- bioaccumulation in aquatic species, other
- Type of information:
- (Q)SAR
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Validated QSAR model. Calculation for degradation product of DEHA.
- Justification for type of information:
- 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.
For details see QMRF and QPRF inserted in "Overall remarks" and executive summary", respectively. - 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: 2.96 (KOWWIN v1.68) - Type:
- BCF
- Value:
- 3.16 L/kg
- Basis:
- whole body w.w.
- Remarks on result:
- other: The substance is within the applicability domain of the BCFBAF submodel: Bioconcentration factor (BCF; Meylan et al., 1997/1999).
- Type:
- BCF
- Value:
- 37.9 L/kg
- Basis:
- whole body w.w.
- Calculation basis:
- steady state
- Remarks on result:
- other: Upper trophic, incl. biotransformation estimates; The substance is within the applicability domain of the BCFBAF submodel: Arnot & Gobas BAF and steady-state BCF Arnot & Gobas, 2003).
- Type:
- BCF
- Value:
- 47.51 L/kg
- Basis:
- whole body w.w.
- Calculation basis:
- steady state
- Remarks on result:
- other: Upper trophic, incl. biotransformation rate of zero; The substance is within the applicability domain of the BCFBAF submodel: Arnot & Gobas BAF and steady-state BCF Arnot & Gobas, 2003).
- Type:
- BAF
- Value:
- 37.9 L/kg
- Basis:
- whole body w.w.
- Remarks on result:
- other: Upper trophic, incl. biotransformation estimates; The substance is within the applicability domain of the BCFBAF submodel: Arnot & Gobas BAF and steady-state BCF Arnot & Gobas, 2003).
- Type:
- BAF
- Value:
- 50.69 L/kg
- Basis:
- whole body w.w.
- Remarks on result:
- other: Upper trophic, incl. biotransformation rate of zero; The substance is within the applicability domain of the BCFBAF submodel: Arnot & Gobas BAF and steady-state BCF Arnot & Gobas, 2003).
- Details on kinetic parameters:
- Biotransformation half-life (days): 0.5184
Biotransformation rate (kM, normalised to 10 g fish at 15 °C): -
The substance is within the applicability domain of the BCFBAF submodel: Biotransformation rate in fish (kM; Arnot et al., 2008a/b). - Executive summary:
QPRF: BCFBAF v3.01
1.
Substance
See “Test material identity”
2.
General information
2.1
Date of QPRF
See “Data Source (Reference)”
2.2
QPRF author and contact details
See “Data Source (Reference)”
3.
Prediction
3.1
Endpoint
(OECD Principle 1)Endpoint
Bioaccumulation (aquatic)
Dependent variable
- Bioconcentration factor (BCF)
- Bioaccumulation factor (BAF; 15 °C)
- Biotransformation rate (kM) and half-life
3.2
Algorithm
(OECD Principle 2)Model or submodel name
BCFBAF
Submodels:
1) Bioconcentration factor (BCF; Meylan et al., 1997/1999)
2) Biotransformation rate in fish (kM; Arnot et al., 2008a/b)
3) Arnot & Gobas BAF and steady-state BCF Arnot & Gobas, 2003)
Model version
v. 3.01
Reference to QMRF
Estimation of Bioconcentration, bioaccumulation and biotransformation in fish using BCFBAF v3.01 (EPI Suite v4.11)
Predicted value (model result)
See “Results and discussion”
Input for prediction
Chemical structure via CAS number or SMILES; log Kow (optional)
Descriptor values
- SMILES: structure of the compound as SMILES notation
- log Kow
- Molecular weight
3.3
Applicability domain
(OECD principle 3)Domains:
1) Bioconcentration factor (BCF; Meylan et al., 1997/1999)
a) Ionic/non-Ionic
The substance is non-ionic.
b) Molecular weight (range of test data set):
- Ionic: 68.08 to 991.80
- Non-ionic: 68.08 to 959.17
(On-Line BCFBAF Help File, Ch. 7.1.3 Estimation Domain and Appendix G)
The substance is within range (370.58 g/mol).
c) log Kow (range of test data set):
- Ionic: -6.50 to 11.26
- Non-ionic: -1.37 to 11.26
(On-Line BCFBAF Help File, Ch. 7.1.3 Estimation Domain and Appendix G)
The substance is within range (8.94).
d) Maximum number of instances of correction factor in any of the training set compounds (On-Line BCFBAF Help File, Appendix E)
Not exceeded.
2) Biotransformation rate in fish (kM; Arnot et al., 2008a/b)
a) The substance does not appreciably ionize at physiological pH.
(On-Line BCFBAF Help File, Ch. 7.2.3)
fulfilled
b) Molecular weight (range of test data set): 68.08 to 959.17
(On-Line BCFBAF Help File, Ch. 7.2.3)
The substance is within range (370.58 g/mol).
c) The molecular weight is ≤ 600 g/mol.
(On-Line BCFBAF Help File, Ch. 7.2.3)
fulfilled
d) Log Kow: 0.31 to 8.70
(On-Line BCFBAF Help File, Ch. 7.2.3)
The substance is not within range (8.94).
e) The substance is no metal or organometal, pigment or dye, or a perfluorinated substance.
(On-Line BCFBAF Help File, Ch. 7.2.3)
fulfilled
f) Maximum number of instances of biotransformation fragments in any of the training set compounds (On-Line BCFBAF Help File, Appendix F)
Not exceeded.
3) Arnot & Gobas BAF and steady-state BCF Arnot & Gobas, 2003)
a) Log Kow ≤ 9
(On-Line BCFBAF Help File, Ch. 7.3.1)
fulfilled
b) The substance does not appreciably ionize.
(On-Line BCFBAF Help File, Ch. 7.3.1)
fulfilled
c) The substance is no pigment, dye, or perfluorinated substance.
(On-Line BCFBAF Help File, Ch. 7.3.1)
fulfilled
3.4
The uncertainty of the prediction
(OECD principle 4)1. Bioconcentration factor (BCF; Meylan et al., 1997/1999)
Statistical accuracy of the training data set (non-ionic plus ionic data):
- Correlation coefficient (r2) = 0.833
- Standard deviation = 0.502 log units
- Absolute mean error = 0.382 log units
2. Biotransformation Rate in Fish (kM)
Statistical accuracy (training set):
- Correlation coefficient (r2) = 0.821
- Correlation coefficient (Q2) = 0.753
- Standard deviation = 0.494 log units
- Absolute mean error = 0.383 log units
3. Arnot-Gobas BAF/BCF model
No information on the statistical accuracy given in the documentation.
3.5
The chemical mechanisms according to the model underpinning the predicted result
(OECD principle 5)1. The BCF model is mainly based on the relationship between bioconcentration and hydrophobicity. The model also takes into account the chemical structure and the ionic/non-ionic character of the substance.
2. Bioaccumulation is the net result of relative rates of chemical inputs to an organism from multimedia exposures (e.g., air, food, and water) and chemical outputs (or elimination) from the organism.
3. The model includes mechanistic processes for bioconcentration and bioaccumulation such as chemical uptake from the water at the gill surface (BCFs and BAFs) and the diet (BAFs only), and chemical elimination at the gill surface, fecal egestion, growth dilution and metabolic biotransformation (Arnot and Gobas 2003). Other processes included in the calculations are bioavailability in the water column (only the freely dissolved fraction can bioconcentrate) and absorption efficiencies at the gill and in the gastrointestinal tract.
References
- Arnot JA, Gobas FAPC. 2003. A generic QSAR for assessing the bioaccumulation potential of organic chemicals in aquatic food webs. QSAR and Combinatorial Science 22: 337-345.
- Arnot JA, Mackay D, Parkerton TF, Bonnell M. 2008a. A database of fish biotransformation rates for organic chemicals. Environmental Toxicology and Chemistry 27(11), 2263-2270.
- Arnot JA, Mackay D, Bonnell M. 2008b.Estimating metabolic biotransformation rates in fish from laboratory data. Environmental Toxicology and Chemistry 27: 341-351.
- Meylan, W.M., Howard, P.H, Aronson, D., Printup, H. and S. Gouchie. 1997. "Improved Method for Estimating Bioconcentration Factor (BCF) from Octanol-Water Partition Coefficient", SRC TR-97-006 (2nd Update), July 22, 1997; prepared for: Robert S. Boethling, EPA-OPPT, Washington, DC; Contract No. 68-D5-0012; prepared by: ; Syracuse Research Corp., Environmental Science Center, 6225 Running Ridge Road, North Syracuse, NY 13212.
- Meylan, WM, Howard, PH, Boethling, RS et al. 1999. Improved Method for Estimating Bioconcentration / Bioaccumulation Factor from Octanol/Water Partition Coefficient. Environ. Toxicol. Chem. 18(4): 664-672 (1999).
- US EPA (2012). On-Line BCFBAF Help File.
Identified Correction Factors (Appendix E), Biotransformation Fragments and Coefficient values (Appendix F)
The Training Set used to derive the Coefficient Values listed below contained a total of 421 compounds (see Appendix I for the compound list).
.
Fragment Description
Coefficient value
No. compounds containing fragment in total training set
Maximum number of each fragment in any individual compound
No. of instances of each fragment for the current substance
Linear C4 terminal chain [CCC-CH3]
0,03412373
43
3
1
Aliphatic acid [-C(=O)-OH]
0,38030117
1
2
1
Methyl [-CH3]
0,24510529
170
12
2
-CH2- [linear]
0,02418707
109
28
4
-CH- [linear]
-0.19123158
50
2
1
Assessment of Applicability Domain Based on Molecular Weight and log Kow
1. Bioconcentration Factor (BCF; Meylan et al., 1997/1999)
Training set: Molecular weights
Ionic
Non-ionic
Minimum
68,08
68,08
Maximum
991,80
959,17
Average
244,00
244,00
Assessment of molecular weight
Molecular weight within range of training set.
Training set: Log Kow
Ionic
Non-ionic
Minimum
-6,50
-1,37
Maximum
11,26
11,26
Assessment of log Kow
Log Kow within range of training set.
2. Biotransformation Rate in Fish (kM; Arnot et al., 2008a/b)
Training set: Molecular weights
Minimum
68,08
Maximum
959,17
Average
259,75
Assessment of molecular weight
Molecular weight within range of training set.
Training set: Log Kow
Minimum
0,31
Maximum
8,70
Assessment of log Kow
Log Kow outside of range of training set. Therefore, the estimate may be less accurate.
- Endpoint:
- bioaccumulation in aquatic species, other
- Type of information:
- (Q)SAR
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Validated QSAR model. Calculation for degradation product of DINA.
- Justification for type of information:
- 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.
For details see QMRF and QPRF inserted in "Overall remarks" and executive summary", respectively. - 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: 3.22 (KOWWIN v1.68) - Type:
- BCF
- Value:
- 62.16 L/kg
- Basis:
- whole body w.w.
- Remarks on result:
- other: The substance is within the applicability domain of the BCFBAF submodel: Bioconcentration factor (BCF; Meylan et al., 1997/1999).
- Type:
- BCF
- Value:
- 71.84 L/kg
- Basis:
- whole body w.w.
- Calculation basis:
- steady state
- Remarks on result:
- other: Upper trophic, incl. biotransformation estimates; The substance is within the applicability domain of the BCFBAF submodel: Arnot & Gobas BAF and steady-state BCF Arnot & Gobas, 2003).
- Type:
- BCF
- Value:
- 178.6 L/kg
- Basis:
- whole body w.w.
- Calculation basis:
- steady state
- Remarks on result:
- other: Upper trophic, incl. biotransformation rate of zero; The substance is within the applicability domain of the BCFBAF submodel: Arnot & Gobas BAF and steady-state BCF Arnot & Gobas, 2003).
- Type:
- BAF
- Value:
- 71.84 L/kg
- Basis:
- whole body w.w.
- Remarks on result:
- other: Upper trophic, incl. biotransformation estimates; The substance is within the applicability domain of the BCFBAF submodel: Arnot & Gobas BAF and steady-state BCF Arnot & Gobas, 2003).
- Type:
- BAF
- Value:
- 218.6 L/kg
- Basis:
- whole body w.w.
- Remarks on result:
- other: Upper trophic, incl. biotransformation rate of zero; The substance is within the applicability domain of the BCFBAF submodel: Arnot & Gobas BAF and steady-state BCF Arnot & Gobas, 2003).
- Details on kinetic parameters:
- Biotransformation half-life (days): 0.2925
Biotransformation rate (kM, normalised to 10 g fish at 15 °C): -
The substance is within the applicability domain of the BCFBAF submodel: Biotransformation rate in fish (kM; Arnot et al., 2008a/b). - Executive summary:
QPRF: BCFBAF v3.01
1.
Substance
See “Test material identity”
2.
General information
2.1
Date of QPRF
See “Data Source (Reference)”
2.2
QPRF author and contact details
See “Data Source (Reference)”
3.
Prediction
3.1
Endpoint
(OECD Principle 1)Endpoint
Bioaccumulation (aquatic)
Dependent variable
- Bioconcentration factor (BCF)
- Bioaccumulation factor (BAF; 15 °C)
- Biotransformation rate (kM) and half-life
3.2
Algorithm
(OECD Principle 2)Model or submodel name
BCFBAF
Submodels:
1) Bioconcentration factor (BCF; Meylan et al., 1997/1999)
2) Biotransformation rate in fish (kM; Arnot et al., 2008a/b)
3) Arnot & Gobas BAF and steady-state BCF Arnot & Gobas, 2003)
Model version
v. 3.01
Reference to QMRF
Estimation of Bioconcentration, bioaccumulation and biotransformation in fish using BCFBAF v3.01 (EPI Suite v4.11)
Predicted value (model result)
See “Results and discussion”
Input for prediction
Chemical structure via CAS number or SMILES; log Kow (optional)
Descriptor values
- SMILES: structure of the compound as SMILES notation
- log Kow
- Molecular weight
3.3
Applicability domain
(OECD principle 3)Domains:
1) Bioconcentration factor (BCF; Meylan et al., 1997/1999)
a) Ionic/non-Ionic
The substance is non-ionic.
b) Molecular weight (range of test data set):
- Ionic: 68.08 to 991.80
- Non-ionic: 68.08 to 959.17
(On-Line BCFBAF Help File, Ch. 7.1.3 Estimation Domain and Appendix G)
The substance is within range (144.26 g/mol).
c) log Kow (range of test data set):
- Ionic: -6.50 to 11.26
- Non-ionic: -1.37 to 11.26
(On-Line BCFBAF Help File, Ch. 7.1.3 Estimation Domain and Appendix G)
The substance is within range (3.22).
d) Maximum number of instances of correction factor in any of the training set compounds (On-Line BCFBAF Help File, Appendix E)
Not exceeded.
2) Biotransformation rate in fish (kM; Arnot et al., 2008a/b)
a) The substance does not appreciably ionize at physiological pH.
(On-Line BCFBAF Help File, Ch. 7.2.3)
fulfilled
b) Molecular weight (range of test data set): 68.08 to 959.17
(On-Line BCFBAF Help File, Ch. 7.2.3)
The substance is within range (144.26 g/mol).
c) The molecular weight is ≤ 600 g/mol.
(On-Line BCFBAF Help File, Ch. 7.2.3)
fulfilled
d) Log Kow: 0.31 to 8.70
(On-Line BCFBAF Help File, Ch. 7.2.3)
The substance is not within range (0.23).
e) The substance is no metal or organometal, pigment or dye, or a perfluorinated substance.
(On-Line BCFBAF Help File, Ch. 7.2.3)
fulfilled
f) Maximum number of instances of biotransformation fragments in any of the training set compounds (On-Line BCFBAF Help File, Appendix F)
Not exceeded.
3) Arnot & Gobas BAF and steady-state BCF Arnot & Gobas, 2003)
a) Log Kow ≤ 9
(On-Line BCFBAF Help File, Ch. 7.3.1)
fulfilled
b) The substance does not appreciably ionize.
(On-Line BCFBAF Help File, Ch. 7.3.1)
fulfilled
c) The substance is no pigment, dye, or perfluorinated substance.
(On-Line BCFBAF Help File, Ch. 7.3.1)
fulfilled
3.4
The uncertainty of the prediction
(OECD principle 4)1. Bioconcentration factor (BCF; Meylan et al., 1997/1999)
Statistical accuracy of the training data set (non-ionic plus ionic data):
- Correlation coefficient (r2) = 0.833
- Standard deviation = 0.502 log units
- Absolute mean error = 0.382 log units
2. Biotransformation Rate in Fish (kM)
Statistical accuracy (training set):
- Correlation coefficient (r2) = 0.821
- Correlation coefficient (Q2) = 0.753
- Standard deviation = 0.494 log units
- Absolute mean error = 0.383 log units
3. Arnot-Gobas BAF/BCF model
No information on the statistical accuracy given in the documentation.
3.5
The chemical mechanisms according to the model underpinning the predicted result
(OECD principle 5)1. The BCF model is mainly based on the relationship between bioconcentration and hydrophobicity. The model also takes into account the chemical structure and the ionic/non-ionic character of the substance.
2. Bioaccumulation is the net result of relative rates of chemical inputs to an organism from multimedia exposures (e.g., air, food, and water) and chemical outputs (or elimination) from the organism.
3. The model includes mechanistic processes for bioconcentration and bioaccumulation such as chemical uptake from the water at the gill surface (BCFs and BAFs) and the diet (BAFs only), and chemical elimination at the gill surface, fecal egestion, growth dilution and metabolic biotransformation (Arnot and Gobas 2003). Other processes included in the calculations are bioavailability in the water column (only the freely dissolved fraction can bioconcentrate) and absorption efficiencies at the gill and in the gastrointestinal tract.
References
- Arnot JA, Gobas FAPC. 2003. A generic QSAR for assessing the bioaccumulation potential of organic chemicals in aquatic food webs. QSAR and Combinatorial Science 22: 337-345.
- Arnot JA, Mackay D, Parkerton TF, Bonnell M. 2008a. A database of fish biotransformation rates for organic chemicals. Environmental Toxicology and Chemistry 27(11), 2263-2270.
- Arnot JA, Mackay D, Bonnell M. 2008b.Estimating metabolic biotransformation rates in fish from laboratory data. Environmental Toxicology and Chemistry 27: 341-351.
- Meylan, W.M., Howard, P.H, Aronson, D., Printup, H. and S. Gouchie. 1997. "Improved Method for Estimating Bioconcentration Factor (BCF) from Octanol-Water Partition Coefficient", SRC TR-97-006 (2nd Update), July 22, 1997; prepared for: Robert S. Boethling, EPA-OPPT, Washington, DC; Contract No. 68-D5-0012; prepared by: ; Syracuse Research Corp., Environmental Science Center, 6225 Running Ridge Road, North Syracuse, NY 13212.
- Meylan, WM, Howard, PH, Boethling, RS et al. 1999. Improved Method for Estimating Bioconcentration / Bioaccumulation Factor from Octanol/Water Partition Coefficient. Environ. Toxicol. Chem. 18(4): 664-672 (1999).
- US EPA (2012). On-Line BCFBAF Help File.
Identified Correction Factors (Appendix E), Biotransformation Fragments and Coefficient values (Appendix F) and
Assessment of Applicability Domain Based on Molecular Weight and log Kow
Appendix E: BCF Non-Ionic Correction Factors Used by BCFBAF The Training Set used to derive the BCF Correction Factors listed below contained a total of 431 compounds (see Appendix G for the compound list). The number of compounds in the training set with logKow values of 1.0 to 7.0 total 396 compounds ... 35 training set compounds have a logKow value greater than 7.0 ... Compounds with logKow less than 1.0 were not used to derive correction factors. Correction Factor BCFBAF No. compounds containing factor in training set Maximum number of each fragment in any individual compound No. of instances of each fragment for the current substance Appendix F: kM Biotransformation Fragments & Coefficient Values . The Training Set used to derive the Coefficient Values listed below contained a total of 421 compounds (see Appendix I for the compound list). . Fragment Description Coefficient value No. compounds containing fragment in total training set Maximum number of each fragment in any individual compound No. of instances of each fragment for the current substance Aliphatic alcohol [-OH] -0,06155701 7 3 1 Methyl [-CH3] 0,24510529 170 12 2 -CH2- [linear] 0,02418707 109 28 6 -CH- [linear] -0.19123158 50 2 1 Assessment of applicability domain based on molecular weight and log Kow . 1. Bioconcentration Factor (BCF; Meylan et al., 1997/1999) . Training set: Molecular weights Ionic Non-ionic . Minimum 68,08 68,08 . Maximum 991,80 959,17 . Average 244,00 244,00 . Assessment of molecular weight Molecular weight within range of training set. . . Training set: Log Kow Ionic Non-ionic . Minimum -6,50 -1,37 . Maximum 11,26 11,26 . Assessment of log Kow Log Kow within range of training set. . . 2. Biotransformation Rate in Fish (kM; Arnot et al., 2008a/b) . Training set: Molecular weights . Minimum 68,08 . Maximum 959,17 . Average 259,75 . Assessment of molecular weight Molecular weight within range of training set. . . Training set: Log Kow . Minimum 0,31 . Maximum 8,70 . Assessment of log Kow Log Kow within range of training set. . .
Referenceopen allclose all
Throughout the study, 2 deaths occurred in the solvent control and one death in the control.
Throughout the study, 2 deaths occurred in the solvent control.
Summary Results:
Log BCF (regression-based estimate): 2.43 (BCF = 268 L/kg wet-wt)
Biotransformation Half-Life (days) : 0.635 (normalized to 10 g fish)
Log BAF (Arnot-Gobas upper trophic): 0.08 (BAF = 1.21 L/kg wet-wt)
Experimental BCF-kM Database Structure Match:
--------------------------------------------
Name : Diisononyl adipate
CAS Num : 090411-51-1
Log BCF : ---
BCF Data : ---
Log Bio HL: -0.609 (Bio Half-life = 0.246 days)
Bio Data : kM Training Set
Log Kow (experimental): not available from database
Log Kow used by BCF estimates: 9.24
Equation Used to Make BCF estimate:
Log BCF = -0.49 log Kow + 7.554 + Correction
Correction(s): Value
Alkyl chains (8+ -CH2- groups) -0.596
Estimated Log BCF = 2.428 (BCF = 267.7 L/kg wet-wt)
===========================================================
Whole Body Primary Biotransformation Rate Estimate for Fish:
===========================================================
------+-----+--------------------------------------------+---------+---------
TYPE | NUM | LOG BIOTRANSFORMATION FRAGMENT DESCRIPTION | COEFF | VALUE
------+-----+--------------------------------------------+---------+---------
Frag | 2 | Linear C4 terminal chain [CCC-CH3] | 0.0341 | 0.0682
Frag | 2 | Ester [-C(=O)-O-C] | -0.7605 | -1.5211
Frag | 2 | Methyl [-CH3] | 0.2451 | 0.4902
Frag | 20 | -CH2- [linear] | 0.0242 | 0.4837
L Kow| * | Log Kow = 9.24 (KowWin estimate) | 0.3073 | 2.8413
MolWt| * | Molecular Weight Parameter | | -1.0222
Const| * | Equation Constant | | -1.5058
============+============================================+=========+=========
RESULT | LOG Bio Half-Life (days) | | -0.1969
RESULT | Bio Half-Life (days) | | 0.6355
NOTE | Bio Half-Life Normalized to 10 g fish at 15 deg C |
============+============================================+=========+=========
Biotransformation Rate Constant:
kM (Rate Constant): 1.091 /day (10 gram fish)
kM (Rate Constant): 0.6134 /day (100 gram fish)
kM (Rate Constant): 0.3449 /day (1 kg fish)
kM (Rate Constant): 0.194 /day (10 kg fish)
Note: For Arnot-Gobas BCF & BAF Methods, Experimental Km Half-Life Used:
Exp Km Half-Life = -0.609 days (Rate Constant = 2.817/ day)
Arnot-Gobas BCF & BAF Methods (including biotransformation rate estimates):
Estimated Log BCF (upper trophic) = 0.069 (BCF = 1.171 L/kg wet-wt)
Estimated Log BAF (upper trophic) = 0.082 (BAF = 1.207 L/kg wet-wt)
Estimated Log BCF (mid trophic) = 0.118 (BCF = 1.313 L/kg wet-wt)
Estimated Log BAF (mid trophic) = 0.581 (BAF = 3.808 L/kg wet-wt)
Estimated Log BCF (lower trophic) = 0.134 (BCF = 1.361 L/kg wet-wt)
Estimated Log BAF (lower trophic) = 1.403 (BAF = 25.3 L/kg wet-wt)
Arnot-Gobas BCF & BAF Methods (assuming a biotransformation rate of zero):
Estimated Log BCF (upper trophic) = 2.642 (BCF = 438.5 L/kg wet-wt)
Estimated Log BAF (upper trophic) = 6.338 (BAF = 2.175e+006 L/kg wet-wt)
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.
Carboxylesterases are a class of enzymes responsible for the ester cleavage of carboxylic esters. Liver B-carboxylesterases are the most prominent group of all “nonspecific” ester-cleaving enzymes. The preferred substrates of B-esterases are aliphatic esters. B-type esterases have been characterized in human muscle, kidney, brain, liver and serum of mammals. The activity of B-esterase from pig and rat liver was shown for several carboxylesters (e.g. methyl octanoate, heptyl acetate).
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.
Esters do not readily bioaccumulate in fish. This might be caused by the wide carboxyesterase distribution, high tissue content, rapid substrate turnover and limited substrate specificity.
MODEL DOMAIN
Parametric domain: In domain: (100%)
Structural domain: In domain (100%)
Mechanistic domain: In domain (100%)
DOMAIN APPLICABILITY
With regard to the parametric, structural and mechanistic domain, the test substance is within the applicability domain of the model.
Summary Results:
Log BCF (regression-based estimate): 2.98 (BCF = 957 L/kg wet-wt)
Biotransformation Half-Life (days) : 0.309 (normalized to 10 g fish)
Log BAF (Arnot-Gobas upper trophic): 0.79 (BAF = 6.18 L/kg wet-wt)
Log Kow (experimental): not available from database
Log Kow used by BCF estimates: 8.12
Equation Used to Make BCF estimate:
Log BCF = -0.49 log Kow + 7.554 + Correction
Correction(s): Value
Alkyl chains (8+ -CH2- groups) -0.596
Estimated Log BCF = 2.981 (BCF = 957.1 L/kg wet-wt)
Whole Body Primary Biotransformation Rate Estimate for Fish:
TYPE | NUM | LOG BIOTRANSFORMATION FRAGMENT DESCRIPTION | COEFF | VALUE
------+-----+--------------------------------------------+---------+---------
Frag | 2 | Linear C4 terminal chain [CCC-CH3] | 0.0341 | 0.0682
Frag | 2 | Ester [-C(=O)-O-C] | -0.7605 | -1.5211
Frag | 4 | Methyl [-CH3] | 0.2451 | 0.9804
Frag | 14 | -CH2- [linear] | 0.0242 | 0.3386
Frag | 2 | -CH- [linear] | -0.1912 | -0.3825
L Kow| * | Log Kow = 8.12 (KowWin estimate) | 0.3073 | 2.4942
MolWt| * | Molecular Weight Parameter | | -0.9503
Const| * | Equation Constant | | -1.5058
RESULT | LOG Bio Half-Life (days) | | -0.5094
RESULT | Bio Half-Life (days) | | 0.3095
NOTE | Bio Half-Life Normalized to 10 g fish at 15 deg C |
Biotransformation Rate Constant:
kM (Rate Constant): 2.24 /day (10 gram fish)
kM (Rate Constant): 1.26 /day (100 gram fish)
kM (Rate Constant): 0.7083 /day (1 kg fish)
kM (Rate Constant): 0.3983 /day (10 kg fish)
Arnot-Gobas BCF & BAF Methods (including biotransformation rate estimates):
Estimated Log BCF (upper trophic) = 0.736 (BCF = 5.447 L/kg wet-wt)
Estimated Log BAF (upper trophic) = 0.791 (BAF = 6.183 L/kg wet-wt)
Estimated Log BCF (mid trophic) = 0.857 (BCF = 7.19 L/kg wet-wt)
Estimated Log BAF (mid trophic) = 1.676 (BAF = 47.39 L/kg wet-wt)
Estimated Log BCF (lower trophic) = 0.894 (BCF = 7.84 L/kg wet-wt)
Estimated Log BAF (lower trophic) = 2.546 (BAF = 351.8 L/kg wet-wt)
Arnot-Gobas BCF & BAF Methods (assuming a biotransformation rate of zero):
Estimated Log BCF (upper trophic) = 3.477 (BCF = 2999 L/kg wet-wt)
Estimated Log BAF (upper trophic) = 7.067 (BAF = 1.167e+007 L/kg wet-wt)
MODEL DOMAIN
Parametric domain: In domain: (100%)
Structural domain: In domain (100%)
Mechanistic domain: In domain (100%)
DOMAIN APPLICABILITY
With regard to the parametric, structural and mechanistic domain, the test substance is within the applicability domain of the model.
MOLECULE SIZE
Maximum diameter: 18.78 (13.82 – 26.58) Å
EFFECTS OF MITIGATING FACTORS
Mitigating factor |
Predicted value |
Reduction in relation to BCF without mitigation (as log BCF) |
|
BCF |
log BCF |
||
Without mitigation |
6918.3 |
3.84 |
- |
Combination of all factors: acids + metabolism + phenols + size + water solubility |
6.76 |
0.83 |
3.01 |
RESUTLS AND DISCUSSION
The BCF base-line model estimates the log BCF for the test item at 0.83 (BCF = 6.76) indicating low potential for bioaccumulation.
The maximum log BCF value was calculated to be 3.84 (BCF = 6918.3). Mitigating factors like metabolism, molecule size and the water solubility were considered by the model.
According to the OECD 305 technical guidance document, the degree of transformation of the parent is decisive for the effect of metabolism (i.e.. the reproduction of subsequent steps is less critical for the prediction of the BCF).
Mainly metabolism and to a low degree molecular size reduce the log BCF as estimated by the model. Molecular size is discussed within the literature whether certain threshold values are suitable as cut-off criteria for indication of limited bioaccumulation. Regarding molecular size, the PBT working group on hazardous substances discussed a maximum diameter of > 17.4 Å (Comber et al., 2006). The mean maximum diameter of the test item is determined to be 18.78 Å with the lowest maximum diameter calculated for the 30 energetically preferred 3D structures of the test item being > 13.82 Å.
Summary Results:
Log BCF (regression-based estimate): 0.50 (BCF = 3.16 L/kg wet-wt)
Biotransformation Half-Life (days) : 0.0933 (normalized to 10 g fish)
Log BAF (Arnot-Gobas upper trophic): -0.00 (BAF = 0.994 L/kg wet-wt)
Log Kow (experimental): 0.08
Log Kow used by BCF estimates: 0.08
Equation Used to Make BCF estimate:
Log BCF = 0.50 (Ionic; Log Kow dependent)
Estimated Log BCF = 0.500 (BCF = 3.162 L/kg wet-wt)
===========================================================
Whole Body Primary Biotransformation Rate Estimate for Fish:
===========================================================
------+-----+--------------------------------------------+---------+---------
TYPE | NUM | LOG BIOTRANSFORMATION FRAGMENT DESCRIPTION | COEFF | VALUE
------+-----+--------------------------------------------+---------+---------
Frag | 2 | Aliphatic acid [-C(=O)-OH] | 0.3803 | 0.7606
Frag | 4 | -CH2- [linear] | 0.0242 | 0.0967
L Kow| * | Log Kow = 0.08 (experimental ) | 0.3073 | 0.0246
MolWt| * | Molecular Weight Parameter | | -0.3748
Const| * | Equation Constant | | -1.5058
============+============================================+=========+=========
RESULT | LOG Bio Half-Life (days) | | -1.0299
RESULT | Bio Half-Life (days) | | 0.09335
NOTE | Bio Half-Life Normalized to 10 g fish at 15 deg C |
============+============================================+=========+=========
Biotransformation Rate Constant:
kM (Rate Constant): 7.425 /day (10 gram fish)
kM (Rate Constant): 4.176 /day (100 gram fish)
kM (Rate Constant): 2.348 /day (1 kg fish)
kM (Rate Constant): 1.32 /day (10 kg fish)
Arnot-Gobas BCF & BAF Methods (including biotransformation rate estimates):
Estimated Log BCF (upper trophic) = -0.003 (BCF = 0.9942 L/kg wet-wt)
Estimated Log BAF (upper trophic) = -0.003 (BAF = 0.9942 L/kg wet-wt)
Estimated Log BCF (mid trophic) = 0.002 (BCF = 1.005 L/kg wet-wt)
Estimated Log BAF (mid trophic) = 0.002 (BAF = 1.005 L/kg wet-wt)
Estimated Log BCF (lower trophic) = 0.002 (BCF = 1.006 L/kg wet-wt)
Estimated Log BAF (lower trophic) = 0.002 (BAF = 1.006 L/kg wet-wt)
Arnot-Gobas BCF & BAF Methods (assuming a biotransformation rate of zero):
Estimated Log BCF (upper trophic) = 0.009 (BCF = 1.022 L/kg wet-wt)
Estimated Log BAF (upper trophic) = 0.010 (BAF = 1.023 L/kg wet-wt)
Summary Results:
Log BCF (regression-based estimate): 0.50 (BCF = 3.16 L/kg wet-wt)
Biotransformation Half-Life (days) : 0.518 (normalized to 10 g fish)
Log BAF (Arnot-Gobas upper trophic): 1.58 (BAF = 37.9 L/kg wet-wt)
Log Kow (experimental): 2.64
Log Kow used by BCF estimates: 2.64
Equation Used to Make BCF estimate:
Log BCF = 0.50 (Ionic; Log Kow dependent)
Estimated Log BCF = 0.500 (BCF = 3.162 L/kg wet-wt)
===========================================================
Whole Body Primary Biotransformation Rate Estimate for Fish:
===========================================================
------+-----+--------------------------------------------+---------+---------
TYPE | NUM | LOG BIOTRANSFORMATION FRAGMENT DESCRIPTION | COEFF | VALUE
------+-----+--------------------------------------------+---------+---------
Frag | 1 | Linear C4 terminal chain [CCC-CH3] | 0.0341 | 0.0341
Frag | 1 | Aliphatic acid [-C(=O)-OH] | 0.3803 | 0.3803
Frag | 2 | Methyl [-CH3] | 0.2451 | 0.4902
Frag | 4 | -CH2- [linear] | 0.0242 | 0.0967
Frag | 1 | -CH- [linear] | -0.1912 | -0.1912
L Kow| * | Log Kow = 2.64 (experimental ) | 0.3073 | 0.8114
MolWt| * | Molecular Weight Parameter | | -0.3698
Const| * | Equation Constant | | -1.5058
============+============================================+=========+=========
RESULT | LOG Bio Half-Life (days) | | -0.2853
RESULT | Bio Half-Life (days) | | 0.5184
NOTE | Bio Half-Life Normalized to 10 g fish at 15 deg C |
============+============================================+=========+=========
Biotransformation Rate Constant:
kM (Rate Constant): 1.337 /day (10 gram fish)
kM (Rate Constant): 0.7519 /day (100 gram fish)
kM (Rate Constant): 0.4228 /day (1 kg fish)
kM (Rate Constant): 0.2378 /day (10 kg fish)
Arnot-Gobas BCF & BAF Methods (including biotransformation rate estimates):
Estimated Log BCF (upper trophic) = 1.579 (BCF = 37.94 L/kg wet-wt)
Estimated Log BAF (upper trophic) = 1.579 (BAF = 37.94 L/kg wet-wt)
Estimated Log BCF (mid trophic) = 1.441 (BCF = 27.6 L/kg wet-wt)
Estimated Log BAF (mid trophic) = 1.441 (BAF = 27.6 L/kg wet-wt)
Estimated Log BCF (lower trophic) = 1.394 (BCF = 24.76 L/kg wet-wt)
Estimated Log BAF (lower trophic) = 1.394 (BAF = 24.78 L/kg wet-wt)
Arnot-Gobas BCF & BAF Methods (assuming a biotransformation rate of zero):
Estimated Log BCF (upper trophic) = 1.677 (BCF = 47.51 L/kg wet-wt)
Estimated Log BAF (upper trophic) = 1.705 (BAF = 50.69 L/kg wet-wt)
Summary Results:
Log BCF (regression-based estimate): 1.79 (BCF = 62.2 L/kg wet-wt)
Biotransformation Half-Life (days) : 0.292 (normalized to 10 g fish)
Log BAF (Arnot-Gobas upper trophic): 1.86 (BAF = 71.8 L/kg wet-wt)
Log Kow (experimental): not available from database
Log Kow used by BCF estimates: 3.22
Equation Used to Make BCF estimate:
Log BCF = 0.6598 log Kow - 0.333 + Correction
Correction(s): Value
No Applicable Correction Factors
Estimated Log BCF = 1.794 (BCF = 62.16 L/kg wet-wt)
===========================================================
Whole Body Primary Biotransformation Rate Estimate for Fish:
===========================================================
------+-----+--------------------------------------------+---------+---------
TYPE | NUM | LOG BIOTRANSFORMATION FRAGMENT DESCRIPTION | COEFF | VALUE
------+-----+--------------------------------------------+---------+---------
Frag | 1 | Aliphatic alcohol [-OH] | -0.0616 | -0.0616
Frag | 2 | Methyl [-CH3] | 0.2451 | 0.4902
Frag | 6 | -CH2- [linear] | 0.0242 | 0.1451
Frag | 1 | -CH- [linear] | -0.1912 | -0.1912
L Kow| * | Log Kow = 3.22 (KowWin estimate) | 0.3073 | 0.9906
MolWt| * | Molecular Weight Parameter | | -0.3699
Const| * | Equation Constant | | -1.5058
============+============================================+=========+=========
RESULT | LOG Bio Half-Life (days) | | -0.5339
RESULT | Bio Half-Life (days) | | 0.2925
NOTE | Bio Half-Life Normalized to 10 g fish at 15 deg C |
============+============================================+=========+=========
Biotransformation Rate Constant:
kM (Rate Constant): 2.37 /day (10 gram fish)
kM (Rate Constant): 1.333 /day (100 gram fish)
kM (Rate Constant): 0.7494 /day (1 kg fish)
kM (Rate Constant): 0.4214 /day (10 kg fish)
Arnot-Gobas BCF & BAF Methods (including biotransformation rate estimates):
Estimated Log BCF (upper trophic) = 1.856 (BCF = 71.84 L/kg wet-wt)
Estimated Log BAF (upper trophic) = 1.856 (BAF = 71.84 L/kg wet-wt)
Estimated Log BCF (mid trophic) = 1.832 (BCF = 67.95 L/kg wet-wt)
Estimated Log BAF (mid trophic) = 1.832 (BAF = 67.97 L/kg wet-wt)
Estimated Log BCF (lower trophic) = 1.813 (BCF = 64.97 L/kg wet-wt)
Estimated Log BAF (lower trophic) = 1.814 (BAF = 65.15 L/kg wet-wt)
Arnot-Gobas BCF & BAF Methods (assuming a biotransformation rate of zero):
Estimated Log BCF (upper trophic) = 2.252 (BCF = 178.6 L/kg wet-wt)
Estimated Log BAF (upper trophic) = 2.340 (BAF = 218.6 L/kg wet-wt)
Description of key information
Diisononyl adipate does not significantly accumulate in organisms.
Key value for chemical safety assessment
Additional information
Since no reliable studies investigating the bioaccumulation potential of Diisononyl adipate (DINA, CAS 33703-08-1) are available, in accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5 Grouping of substances, a read-across to the structurally very similar Bis(2-ethylhexyl) adipate (CAS 103-23-1, DEHA) was conducted. The read across is justified due to the similarity of structure and functional groups and accordingly similar physico-chemical properties which result in similar environmental behavior and fate (see table below).
Substance |
Diisononyl adipate |
Bis(2-ethylhexyl) adipate |
CAS number |
33703-08-1 |
103-23-1 |
Structure |
see attachment |
see attachment |
Molecular formula |
C24H46O4 |
C22H42O4 |
Molecular weight |
398.63 g/mole |
370.58 g/mole |
PC parameter |
|
|
Water solubility |
RA to 103-23-1 |
0.0032 mg/L (EU A.6) |
Partition coefficient |
9.54 (OECD 117) |
8.94 (OECD 117) |
Vapour pressure |
0.00000002 hPa at 20 °C (calculation) |
0.0000003 hPa at 20 °C (calculation) |
Environmental fate |
|
|
Biodegradability |
> 90% in 28 days (OECD 301F) |
>90% in 28 days (OECD 301F) |
Adsorption [log KOC] |
5.15 (calculation) |
4.56 (calculation) |
Hydrolysis |
not relevant |
|
Ecotoxicology |
|
|
Short-term toxicity to fish [96h-LC50] |
No toxicity within the limit of water solubility |
No toxicity within the limit of water solubility |
Long-term toxicity to aquatic invertebrates [NOEC] |
- |
- |
Short-term toxicity to aquatic invertebrates [48h-EC50] |
No toxicity within the limit of water solubility |
No toxicity within the limit of water solubility |
Long-term toxicity to aquatic invertebrates [21d-NOEC] |
RA from 103 -23 -1 |
No toxicity within the limit of water solubility |
Short-term toxicity to algae [72h-EC50] |
No toxicity within the limit of water solubility |
No toxicity within the limit of water solubility |
Long-term toxicity to algae [72h-NOEC/EC10] |
No toxicity within the limit of water solubility |
No toxicity within the limit of water solubility |
Toxicity to microorganisms [NOEC] |
The inhibition of the degradation activity of activated sludge is not anticipated when DINA is introduced in appropriate low concentrations. |
The inhibition of the degradation activity of activated sludge is not anticipated when DEHA is introduced in appropriate low concentrations. |
The potential for accumulation of the poorly soluble, highly lipophilic 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 metabolism. Furthermore, when transferred to freshwater, the substance is apparently rapidly and extensively excreted from the fish. Similar results were observed in monkeys, rats and mice (see chapter 7.1.1 of the dossier for 103-23-1 published on the ECHA website). Based on the mentioned structural similarities between the source and the target substance resulting in a similar efate and ecotoxicological profile, this experimentally determined BCF value is considered to also adequately assess the bioaccumulation potential of Diisononyl adipate (CAS 33703-08-1).
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 DINA and DEHA 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., 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 and Melancon 1980, Lech and Bend 1980).
Isononanol (DINA), 2-ethylhexanol (DEHA) and adipic acid are the expected hydrolysis products from the enzymatic reaction catalyzed by carboxylesterase. These metabolites exhibit no potential for bioaccumulation (BCF < 80, 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).
These assumptions are confirmed by metabolism studies performed with DEHA or the hydrolysis product 2-ethylhexanol (2-EH) in rats. Guest et al. (1985) showed that at a single oral dose (of 50 or 500 mg/kg 14C-labeled) DEHA, B6C3F1 mice excreted 91, 7, and 1 to 2 % of the radioactive dose in the urine, feces, and expired air in 24 hours, respectively. El-Hawari et al. (1985) administered 500 mg/kg of 14C-labeled DEHA to test animals and in 24 hours observed over 91 percent and 74 percent of the administered dose in the urine of mice and rats, respectively. Takahashi et al. (1981) administered a single oral dose of 500 mg/kg to two male Wistar rats. Eighty-six percent of the administered dose was excreted within 24 hours and over 90 percent of the dose in 48 hours. Roughly equal amounts of radioactivitywere excreted in breath and urine. Deisinger et al. (1994) conducted excretion balance studies with 2-EH in female Fischer 344 rats following single high and low oral doses, repeated oral dosing and dermal exposure. The high, low and repeated low oral dose studies showed similar excretion balance profiles with some evidence of metabolic saturation at the high dose. No evidence of metabolic induction was seen following repeated low oral dosing. All of the oral doses were eliminated rapidly, predominantly in the urine during the first 24 h following dosing. The dermal dosing resulted in only about 5% absorption of the 1 g/kg dose, with the major portion of the dose recovered unabsorbed from the dermal exposure cell at 6h. Urinary metabolites eliminated following the oral and dermal doses were predominately glucuronides of oxidized metabolites, including glucuronides of 2-ethyladipic acid, 2-ethylhexanoic acid, 5-hydroxy-2-ethylhexanoic acid and 6-hydroxy-2-ethylhexanoic acid. Albro (1975) found that 14C associated with 2-ethyl[14C]hexanol was rapidly excreted in respiratory CO2 (6-7%), faeces (8-9%) and urine (80-82%), with essentially complete elimination by 28 h after administration. The amount of label recovered in 14CO2 matched the amount of unlabelled 2-heptanone plus 4-heptanone recovered from urine, suggesting that both types of metabolite may have been derived from the major urinary metabolite, 2-ethyl-hexanoic acid, by decarboxylation following partialβ-oxidation.El-Hawariet al.(1985) administered radiolabeled DEHA to Cynomolgus monkeys via the oral route and found that 49-69 percent of the radioactivity was excreted in the urine and 23-40 percent in the feces by 48 hours after administration.
Metabolism data for adipic acid in aquatic organisms is not available. However, metabolism of adipic acid in rats has been studied by Rusoffet 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.
Two conflicting result are available. One study reports BCF values of 20770 for DEHA and 11000 for DINA in the common mussel Mytilus edulis (Brown 1984a) and the other study BCF values of 815 for DEHA and 1100 – 2000 for DINA in Daphnia magna(Brown 1984b). The lower test concentration used in the study with the mussel was 5 µg/L, which is above the water solubility of the substances (3.2 µg/L).
Acetone was used as vehicle for the test solution preparation in both studies. On the one hand the mussels and daphnids might well have filtered and ingested undissolved material, adding to their body burden. Additionally, mussels and daphnids were fed microalgae. Again, animals possibly have taken up undissolved test material, which has been attached to the surface of or incorporated by the algae. Finally and most importantly, measurements were based on 14C-activity and not on the substance itself. Thus, radioactivity measured in the mussels and daphnids may be due to (i) incorporation of 14C during metabolic processes (see metabolism of adipic acid) or via ingestion of algae, which assimilated 14CO2. In summary, the results of the studies – if at all valid – are likely to clearly overestimate the bioaccumulation potential of bis(2-ethylhexyl) adipate. Therefore, and since more valid information is available, the studies are not taken into account to assess the bioaccumulation potential of diisononyl adipate.
Conclusion
DINA 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, DINA (and its metabolites) 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 DINA by carboxylesterases into adipic acid and isononanol 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 for the suitable read across substance DEHA 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 EPISuite and Catalogic models, 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 DINA and its metabolites.
References
Albro PW. 1975. The metabolism of 2-ethylhexanol in rats. Xenobiotica 5: 625-636
Barron MG et al. 1999. Tissue carboxylesterase activity of rainbow trout. Environ Toxicol Chem 18(11): 2506-2511
Deisinger PJ, Boatman RJ, Guest D. 1994. Metabolism of 2-ethylhexanol administered orally and dermally to the female Fischer 344 rat. Xenobiotica 24(5): 429-440
El-Hawari M, Murrill E, Stoltz M, Skalsky H, Guest D. 1985. Species differences in the disposition and metabolism of di-(2-ethylhexyl)adipate (DEHA).Toxicologist 5: 237
Felder et al. 1986. Assessment of the safety of dioctyl adipate in freshwater environments. Environ Toxicol Chem 5: 777-784
Guest D, Pallas F, Northup S, Moran E, El-Hawari M. 1985. Metabolic studies with di(2-ethylhexyl)adipate (DEHA) in the mouse.Toxicologist 5: 237
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
Hargrove JL. 2004. Nutritional significance and metabolism of very long chain fatty alcohols and acids from dietary waxes. Exp Biol Med 229: 215-226
Lassen N et al. 2005. Molecular cloning, baculovirus expression and tissue distribution of the zebrafish aldehyde dehydrogenase 2. Drug Metabol Disposit 33(5): 649-656
Lech JJ and Bend JR. 1980. Relationship between biotransformation and the toxicity and fate of xenobiotic chemicals in fish. Environmental Health Perspectives 34: 115-131
Lech JJ and Melancon MJ. 1980. Uptake, metabolism, and elimination of 14c‐labeled 1,2,4‐trichlorobenzene in rainbow trout and carp. J Toxicol Environ health 6(3): 645-658
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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
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