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Diss Factsheets

Environmental fate & pathways

Bioaccumulation: aquatic / sediment

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Endpoint:
bioaccumulation in aquatic species: fish
Data waiving:
other justification
Justification for data waiving:
other:
Endpoint:
bioaccumulation in aquatic species: fish
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification
Remarks:
The substance is not fully compliant with the applicability domain of the model. However, this calculation is used in a weight of evidence approach or as a supporting study, in accordance to the REACh Regulation (EC) No 1907/2006, Annex XI General rules for adaptation of the standard testing regime set out in Annexes VII to X, 1.2. It is adequately documented and justified. For more details, see field “overall remarks, attachments”.
Justification for type of information:
1. SOFTWARE
Vega version 1.1.5

2. MODEL (incl. version number)
BCF model (Arnot-Gobas) v1.0.0

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See “Test material information”

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
Further information on the OECD criteria as outlined by the applicant is provided below under "Any other information on materials and methods incl. tables"

5. APPLICABILITY DOMAIN
See attached information and information as provided in the "Overall remarks, attachments" section.

6. ADEQUACY OF THE RESULT
See assessment of adequacy as outlined in the "Overall remarks, attachments" section.
Qualifier:
according to guideline
Guideline:
other: REACH Guidance on QSARs R.6
Principles of method if other than guideline:
- Software tool(s) used including version: Vega v1.1.5
- Model(s) used: Arnot-Gobas v1.0.0
Full reference and details of the used formulas can be found in:
1. 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.
- Model description: see field 'Justification for non-standard information', 'Attached justification' and 'any other information on material and methods'
- Justification of QSAR prediction: see field 'Justification for type of information', 'Attached justification' and/or 'overall remarks'
GLP compliance:
no
Vehicle:
no
Test organisms (species):
other: Fish
Route of exposure:
other: aqueous and dietary
Test type:
other: calculation
Water / sediment media type:
natural water: freshwater
Details on estimation of bioconcentration:
BASIS FOR CALCULATION OF BCF
- Estimation software: Vega v1.1.5, BCF model (Arnot-Gobas) v1.0.0
- Result based on measured log Pow of: 3.91
Type:
BCF
Value:
26 L/kg
Basis:
whole body w.w.
Remarks on result:
other: including biotransformation, upper trophic
Type:
other: log BCF
Value:
1.42 dimensionless
Basis:
whole body w.w.
Remarks on result:
other: including biotransformation, upper trophic
Type:
BCF
Value:
35 L/kg
Basis:
whole body w.w.
Remarks on result:
other: including biotransformation, mid trophic
Type:
other: log BCF
Value:
1.54
Basis:
whole body w.w.
Remarks on result:
other: including biotransformation, mid trophic
Type:
BCF
Value:
38 L/kg
Basis:
whole body w.w.
Remarks on result:
other: including biotransformation, lower trophic
Type:
other: log BCF
Value:
1.58
Basis:
whole body w.w.
Remarks on result:
other: including biotransformation, lower trophic

For detailed information on the results please refer to the attached report.

Endpoint:
bioaccumulation in aquatic species: fish
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification
Remarks:
The substance is not fully compliant with the applicability domain of the model. However, this calculation is used in a weight of evidence approach, in accordance to the REACh Regulation (EC) No 1907/2006, Annex XI General rules for adaptation of the standard testing regime set out in Annexes VII to X, 1.2. It is adequately documented and justified. For more detail see field `overall remarks, attachments´.
Justification for type of information:
1. SOFTWARE
Vega version 1.1.5

2. MODEL (incl. version number)
BCF Read-Across v1.1.0

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See “Test material information”

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached information on the model provided by the developer. Further information on the OECD criteria as outlined by the applicant is provided below under "Any other information of materials and methods incl. tables"

5. APPLICABILITY DOMAIN
See attached information and information as provided in "Any other information on results incl. tables".

6. ADEQUACY OF THE RESULT
See assessment of adequacy as outlined in the "Overall remarks, attachments" section.
Qualifier:
according to guideline
Guideline:
other: REACH Guidance on QSARs R.6
Principles of method if other than guideline:
- Software tool(s) used including version: Vega v1.1.5
- Model(s) used: BCF Read-Across version 1.1.0
Full reference and details of the used formulas can be found in:
Manganaro, A., Pizzo, F., Lombardo, A., Pogliaghi, A., Benfenati, E., 2016. Predicting persistence in the sediment compartment with a new automatic software based on the k-Nearest Neighbor (k-NN) algorithm. Chemosphere 144, 1624–1630.
- Model description: see field 'Justification for non-standard information', 'Attached justification' and 'any other information on Material and methods'
- Justification of QSAR prediction: see field 'Justification for type of information', 'Attached justification' and/or 'overall remarks'
GLP compliance:
no
Vehicle:
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: Vega version 1.1.5, BCF Read-Across version 1.1.0
Type:
other: log BCF
Value:
1.76 L/kg
Basis:
whole body w.w.

For detailed information on the results please refer to the attached report.

Endpoint:
bioaccumulation in aquatic species: fish
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification
Remarks:
The substance is not fully compliant with the applicability domain of the model. However, this calculation is used in a weight of evidence approach, in accordance to the REACh Regulation (EC) No 1907/2006, Annex XI General rules for adaptation of the standard testing regime set out in Annexes VII to X, 1.2. It is adequately documented and justified. For more detail see field `overall remarks, attachments´.
Justification for type of information:
1. SOFTWARE
Vega version 1.1.5

2. MODEL (incl. version number)
CAESAR v 2.1.14

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See “Test material information”

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached information on the model provided by the developer. Further information on the OECD criteria as outlined by the applicant is provided below under "Any other information of materials and methods incl. tables"

5. APPLICABILITY DOMAIN
See attached information and information as provided in "Any other information on results incl. tables".

6. ADEQUACY OF THE RESULT
See assessment of adequacy as outlined in the "Overall remarks, attachments" section.
Qualifier:
according to guideline
Guideline:
other: REACH Guidance on QSARs R.6
Principles of method if other than guideline:
- Software tool(s) used including version: Vega v1.1.5
- Model(s) used: CAESAR BCF Model version 2.1.14

Full reference and details of the used formulas can be found in:
Zhao, C., Boriani, E., Chana, A., Roncaglioni,A., Benfenati, E. A new hybrid system of QSAR models for predicting bioconcentration factors (BCF). Chemosphere (2008), 73, 1701-1707.
Lombardo A, Roncaglioni A, Boriani E, Milan C, Benfenati E. Assessment and validation of the CAESAR predictive model for bioconcentration factor (BCF) in fish. Chemistry Central Journal (2010), 4 (Suppl 1).
R. Todeschini and V. Consonni (2009) Molecular Descriptors for Chemoinformatics, Wiley-VCH U.S.

- Model description: see field 'Justification for non-standard information', 'Attached justification' and 'any other information on Material and methods'
- Justification of QSAR prediction: see field 'Justification for type of information', 'Attached justification' and/or 'overall remarks'
GLP compliance:
no
Vehicle:
no
Test organisms (species):
other: Fish
Route of exposure:
aqueous
Justification for method:
minimised test method used to support BCF estimates based on QSAR
Test type:
other: calculation
Water / sediment media type:
natural water: freshwater
Details on estimation of bioconcentration:
BASIS FOR CALCULATION OF BCF
- Estimation software: Vega version 1.1.5, CAESAR v 2.1.14
- Result based on calculated log Pow of: 2.93
Type:
BCF
Value:
24 L/kg
Basis:
whole body w.w.
Type:
other: Log BCF
Value:
1.39 dimensionless
Basis:
whole body w.w.

For detailed information on the results please refer to the attached report.

Endpoint:
bioaccumulation in aquatic species: fish
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification
Remarks:
The substance is not fully compliant with the applicability domain of the model. However, this calculation is used in a weight of evidence approach, in accordance to the REACh Regulation (EC) No 1907/2006, Annex XI General rules for adaptation of the standard testing regime set out in Annexes VII to X, 1.2. It is adequately documented and justified. For more detail see field `overall remarks, attachments´.
Justification for type of information:
1. SOFTWARE
Vega version 1.1.5

2. MODEL (incl. version number)
BCF Meylan Model v1.0.3

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See “Test material information”

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached information on the model provided by the developer. Further information on the OECD criteria as outlined by the applicant is provided below under "Any other information of materials and methods incl. tables"

5. APPLICABILITY DOMAIN
See attached information and information as provided in "Any other information on results incl. tables".

6. ADEQUACY OF THE RESULT
See assessment of adequacy as outlined in the "Overall remarks, attachments" section.
Qualifier:
according to guideline
Guideline:
other: REACH Guidance on QSARs R.6
Principles of method if other than guideline:
- Software tool(s) used including version: Vega v1.1.5
- Model(s) used: BCF Meylan Model version 1.0.3

Full reference and details of the used formulas can be found in:
Meylan W.M., Howard P.H., Boethling R.S. et al. Improved Method for Estimating Bioconcentration / Bioaccumulation Factor from Octanol/Water
Partition Coefficient. 1999, Environ. Toxicol. Chem. 18(4): 664-672

- Model description: see field 'Justification for non-standard information', 'Attached justification' and 'any other information on Material and methods'
- Justification of QSAR prediction: see field 'Justification for type of information', 'Attached justification' and/or 'overall remarks'
GLP compliance:
no
Vehicle:
no
Test organisms (species):
other: Fish
Route of exposure:
aqueous
Justification for method:
minimised test method used to support BCF estimates based on QSAR
Test type:
other: calculation
Water / sediment media type:
natural water: freshwater
Details on estimation of bioconcentration:
BASIS FOR CALCULATION OF BCF
- Estimation software: Vega version 1.1.5, Meylan Model version 1.0.3
- Result based on calculated log Pow of: 3.91
Type:
BCF
Value:
177 L/kg
Basis:
whole body w.w.
Type:
other: Log BCF
Value:
2.25 dimensionless
Basis:
whole body w.w.

For detailed information on the results please refer to the attached report.

Description of key information

BCF = 24 - 177 L/kg (VEGA 1.1.5; Meylan Model v1.0.3/CAESAR v2.1.14/Arnot-Gobas v1.1.5)

Log BCF 1.39 - 2.25 (VEGA 1.1.5; Meylan Model v1.0.3/CAESAR v2.1.14/BCF KNN/Read-Across v1.1.0/Arnot-Gobas v1.1.5)

Key value for chemical safety assessment

Additional information

In accordance with column 2 of Annex IX 9.3.2 of EC 1907/2006 bioaccumulation testing in aquatic species is not required as the substance has a low potential for bioaccumulation. The test substance will be hydrolysed within a few days in the relevant pH range (DT50 = 2.3 d; pH 7, 25 °C) and the log Pow values of the hydrolysis products are far below 3 (-2.81 (pH 10) to - 0.18 (pH 4)). At an even higher pH, the log Pow can also be assumed to be negative due to salt formation The log Pow of the target compound itself is below 4.5 (log Pow = 3.80). Simulation studies showed that the substance is quickly eliminated from both water body and sediment, with hydrolysis to the free acid and further biodegradation of this hydrolysis product. DT50 values of 0.19 and 1.5 days at 20 °C (recalculated to 0.4 and 3.2 days at 12 °C) were obtained based on data from soil and water/sediment systems from Europe and the US. Thus, it is not likely that they can be found in the aquatic environment in high concentrations. Furthermore, the estimated low potential for bioaccumulation was supported in a weight of evidence approach by using quantitative structure-activity relationship analysis (QSAR), in accordance to the REACh Regulation (EC) No 1907/2006, Annex XI General rules for adaptation of the standard testing regime set out in Annexes VII to X, 1.2. QSAR model calculations resulted in a BCF ranging from 24 L/kg to 177 L/kg (VEGA 1.1.5; Meylan Model v1.0.3/CAESAR v2.1.14/Arnot-Gobas v1.1.5) and a log BCF ranging from 1.39 to 2.25 (VEGA 1.1.5; Meylan Model v1.0.3/CAESAR v2.1.14/BCF KNN/Read-Across v1.1.0/Arnot-Gobas v1.1.5). The results generated by the Arnot-Gobas model are in line with the expectations, the BCF decreases consistently with increasing biotransformation trophic level: 38 L/Kg (lower trophic) > 35 L/Kg (mid trophic) > 26 L/Kg (upper trophic).

Overall, the similarity indexes calculated by Vega show that the training sets used to build the four models used for the evaluation do not include molecules with a high structural similarity to the target compound isoxadifen-ethyl (this was further confirmed by checking the structures of the reported molecules).

However, the most similar molecule identified in the dataset of the KNN model shares similar structural features with isoxadifen-ethyl. The KNN model generated a good prediction for this molecule (difference between experimental and predicted log BCF was < 0.5). Indeed, Vega assigned a higher reliability to this estimation, compared to those generated by the other models. It is concluded that the predicted log BCF = 1.76 (BCF = 57.5 L/Kg) can be considered as a reliable indication that the BCF of the target molecule is < 2000 L/Kg. Therefore, based on the given data, it can be concluded that the bioaccumulation potential of the target compound isoxadifen-ethyl is low and no further tests are necessary.