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Environmental fate & pathways

Bioaccumulation: aquatic / sediment

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Endpoint:
bioaccumulation in aquatic species: fish
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Study period:
Run on 2013-02
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
Remarks:
The bioconcentration factor (BCF) of the C6 isomer of the substance was evaluated with BCFBAF model v3.01 from EPI Suite v4.1, which fulfilled all OECD principles. The C6 isomer of the substance is within the domain of the BCFBAF model based on the molecular weight and fragments present in the BCFBAF database.
Justification for type of information:
1. SOFTWARE
EPISUITE v4.1

2. MODEL (incl. version number)
BCFBAF v3.01

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
C6 isomer: CCC(=O)(OCC(=O)(OC(C)C1CCCC(C)(C)C1))
log Pow: 4.46 (experimental result)

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached QMRF
- Defined endpoint: Bioconcentration Factor (BCF) and Bioaccumulation Factor (BAF).
- Unambiguous algorithm: BCFBAF v3.01 contains two methods for estimating BCFs. The first BCFBAF method is based on the original BCFWIN model and classifies a compound as either ionic or non-ionic. Ionic compounds include carboxylic acids, sulfonic acids and salts of sulfonic acids, and charged nitrogen compounds (nitrogen with a +5 valence such as quaternary ammonium compounds). All other compounds are classified as non-ionic. The second model for BCF estimation has been expanded to calculate both BCF as well as BAF for three general trophic levels of fish. This method is based on the multiple-linear regression-derived equation which is used by the BCFBAF program to estimate the kM Biotransformation Half-Life.
- Defined domain of applicability: The estimation domain for BCF is based on the number of instances given for each correction factor in any of the training set compounds, and the minimum and maximum values for molecular weight and log Kow.
- Appropriate measures of goodness-of-fit and robustness and predictivity: The following gives statistical information for the BCF training and validation datasets (includes ionic and non-ionic compounds). Number = 527 / r² = 0.833 / std deviation = 0.502 / avg deviation = 0.382. For the BCF validation dataset; Number = 158 / r² = 0.82 / std deviation = 0.59 / avg deviation = 0.46. Arnot-Gobas BCF and BAF statistics for the kM biotransformation half-life of the training dataset are; Number = 421 / r² = 0.821 / std deviation = 0.494 / avg deviation = 0.383. For the kM validation dataset; Number = 211 / r² = 0.734 / std deviation = 0.602 / avg deviation = 0.446.
- Mechanistic interpretation: no data

5. APPLICABILITY DOMAIN
See attached QPRF

6. ADEQUACY OF THE RESULT
See attached QPRF
Qualifier:
according to
Guideline:
other: REACH guidance on QSARs R.6, May 2008
Deviations:
no
Principles of method if other than guideline:
See QMRF and QPRF in "Attached background material" and in "Any other information on materials and methods incl. tables" (the QMRF is only available for the former version of the QSAR model).
GLP compliance:
no
Specific details on test material used for the study:
- log Pow: 4.46 (experimental result)
Radiolabelling:
no
Details on sampling:
Not applicable
Details on preparation of test solutions, spiked fish food or sediment:
Not applicable
Details on test organisms:
Not applicable
Test type:
other: QSAR
Water / sediment media type:
not specified
Hardness:
Not applicable
Test temperature:
Not applicable
pH:
Not applicable
Dissolved oxygen:
Not applicable
TOC:
Not applicable
Salinity:
Not applicable
Details on test conditions:
Not applicable
Nominal and measured concentrations:
Not applicable
Reference substance (positive control):
no
Details on estimation of bioconcentration:
Not applicable
Key result
Type:
BCF
Value:
407 L/kg
Basis:
whole body w.w.
Remarks on result:
other: BCF model using log Kow value.
Key result
Type:
BCF
Value:
23.73 L/kg
Basis:
whole body w.w.
Remarks on result:
other: Arnot-Gobas Method, including a biotransformation rate estimates, lower trophic.
Details on kinetic parameters:
Not applicable
Metabolites:
Not applicable
Results with reference substance (positive control):
Not applicable
Details on results:
Arnot-Gobas Method: Based on the biodegradation potential of the test substance, it's more relevant to consider the result including biotransformation rate estimates instead of the result assuming a biotransformation rate of zero.
Reported statistics:
Not applicable

BCF model, for C6 isomer:

Log Kow (estimated) : 4.45

Log Kow (experimental): not available from database

Log Kow used by BCF estimates: 4.46 (user entered)

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 = 2.610 (BCF = 407.1 L/kg wet-wt)

Arnot-Gobas BCF model (Whole body Primary Biotransformation Rate estimate for fish), for C6 isomer:

TYPE

NUM

LOG BIOTRANSFORMATION FRAGMENT DESCRIPTION

COEFF

VALUE

Frag

Frag

Frag

Frag

Frag

Frag

Frag

L Kow

MolWt

Const

2

1

4

2

1

4

1

*

*

*

Ester [-C(=O)-O-C]

Carbon with 4 single bonds & no hydrogens

Methyl [-CH3]

-CH2- [linear]

-CH- [linear]

-CH2- [cyclic]

-CH- [cyclic]

Log Kow = 4.46 (user-entered)

Molecular Weight Parameter

Equation Constant

-0.7605

-0.2984

0.2451

0.0242

-0.1912

0.0963

0.0126

0.3073

-1.5211

-0.2984

0.9804

0.0484

-0.1912

0.3850

0.0126

1.3707

-0.6933

-1.5058

RESULT

RESULT

NOTE

Log Bio Half-life (days)

Bio Half-life (days)

Bio Half-life Normalized to 10 g fish at 15°C

-1.4440

0.03598

Biotransformation rate constant: kM (rate constant) = 19.27 / day (10 gram fish).

Arnot-Gobas BCFBAF Methods (including biotransformation rate estimates):

Estimated Log BCF (upper trophic) = 1.206 (BCF = 16.06 L/Kg wet-wt).

Estimated Log BCF (mid trophic) = 1.336 (BCF = 21.66 L/Kg wet-wt).

Estimated Log BCF (lower trophic) = 1.375 (BCF = 23.73 L/Kg wet-wt).

Arnot-Gobas BCFBAF Methods (assuming a biotransformation rate of zero):

Estimated Log BCF (upper trophic) = 3.447 (BCF = 2801 L/Kg wet-wt).

Validity criteria fulfilled:
yes
Conclusions:
The BCF for the C6 isomer of the substance is estimated to be 407 L/Kg wet-wt based on the log Kow value and 23.73 L/kg wet-wt based on Arnot-Gobas method (lower trophic, including biotransformation rate estimates).
Executive summary:

The bioconcentration factor (BCF) of the C6 isomer of the substance was evaluated with BCFBAF model v3.01 from EPI Suite v4.1, which fulfilled all OECD principles. The C6 isomer of the substance is within the domain of the BCFBAF model based on the molecular weight and fragments present in the BCFBAF database.

Based on the biodegradation potential of the substance, it's more relevant to consider the result obtain with Arnot-Gobas Method, including biotransformation rate estimates instead of the result obtain with Arnot-Gobas Method, assuming a biotransformation rate of zero. The BCF for the C6 isomer of the substance is estimated to be 407 L/Kg wet-wt based on the log Kow value and 23.73 L/kg wet-wt based on Arnot-Gobas method (lower trophic, including biotransformation rate estimates).

Endpoint:
bioaccumulation in aquatic species: fish
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Study period:
Run on 2013-02
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
Remarks:
The bioconcentration factor (BCF) of the C7 isomer of the substance was evaluated with BCFBAF model v3.01 from EPI Suite v4.1, which fulfilled all OECD principles. The C7 isomer of the substance is within the domain of the BCFBAF model based on the molecular weight and fragments present in the BCFBAF database.
Justification for type of information:
1. SOFTWARE
EPISUITE v4.1

2. MODEL (incl. version number)
BCFBAF v3.01

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
C7 isomer: CCC(=O)OCC(=O)OC1CC(C)(C)CCCC1C
log Pow: 4.46 (experimental result)

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached QMRF
- Defined endpoint: Bioconcentration Factor (BCF) and Bioaccumulation Factor (BAF).
- Unambiguous algorithm: BCFBAF v3.01 contains two methods for estimating BCFs. The first BCFBAF method is based on the original BCFWIN model and classifies a compound as either ionic or non-ionic. Ionic compounds include carboxylic acids, sulfonic acids and salts of sulfonic acids, and charged nitrogen compounds (nitrogen with a +5 valence such as quaternary ammonium compounds). All other compounds are classified as non-ionic. The second model for BCF estimation has been expanded to calculate both BCF as well as BAF for three general trophic levels of fish. This method is based on the multiple-linear regression-derived equation which is used by the BCFBAF program to estimate the kM Biotransformation Half-Life.
- Defined domain of applicability: The estimation domain for BCF is based on the number of instances given for each correction factor in any of the training set compounds, and the minimum and maximum values for molecular weight and log Kow.
- Appropriate measures of goodness-of-fit and robustness and predictivity: The following gives statistical information for the BCF training and validation datasets (includes ionic and non-ionic compounds). Number = 527 / r² = 0.833 / std deviation = 0.502 / avg deviation = 0.382. For the BCF validation dataset; Number = 158 / r² = 0.82 / std deviation = 0.59 / avg deviation = 0.46. Arnot-Gobas BCF and BAF statistics for the kM biotransformation half-life of the training dataset are; Number = 421 / r² = 0.821 / std deviation = 0.494 / avg deviation = 0.383. For the kM validation dataset; Number = 211 / r² = 0.734 / std deviation = 0.602 / avg deviation = 0.446.
- Mechanistic interpretation: no data

5. APPLICABILITY DOMAIN
See attached QPRF

6. ADEQUACY OF THE RESULT
See attached QPRF
Qualifier:
according to
Guideline:
other: REACH guidance on QSARs R.6, May 2008
Deviations:
no
Principles of method if other than guideline:
See QMRF and QPRF in "Attached background material" and in "Any other information on materials and methods incl. tables" (the QMRF is only available for the former version of the QSAR model).
GLP compliance:
no
Specific details on test material used for the study:
- log Pow: 4.46 (experimental result)
Radiolabelling:
no
Details on sampling:
Not applicable
Details on preparation of test solutions, spiked fish food or sediment:
Not applicable
Details on test organisms:
Not applicable
Test type:
other: QSAR
Water / sediment media type:
not specified
Hardness:
Not applicable
Test temperature:
Not applicable
pH:
Not applicable
Dissolved oxygen:
Not applicable
TOC:
Not applicable
Salinity:
Not applicable
Details on test conditions:
Not applicable
Nominal and measured concentrations:
Not applicable
Reference substance (positive control):
no
Details on estimation of bioconcentration:
Not applicable
Key result
Type:
BCF
Value:
407 L/kg
Basis:
whole body w.w.
Remarks on result:
other: BCF model using log Kow value.
Key result
Type:
BCF
Value:
37.08 L/kg
Basis:
whole body w.w.
Remarks on result:
other: Arnot-Gobas Method, including biotransformation rate estimates, lower trophic
Details on kinetic parameters:
Not applicable
Metabolites:
Not applicable
Results with reference substance (positive control):
Not applicable
Details on results:
Arnot-Gobas Method: Based on the biodegradation potential of the test substance, it's more relevant to consider the result including biotransformation rate estimates instead of the result assuming a biotransformation rate of zero.
Reported statistics:
Not applicable

BCF model, for C7 isomer:

Log Kow (estimated) : 4.45

Log Kow (experimental): not available from database

Log Kow used by BCF estimates: 4.46 (user entered)

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 = 2.610 (BCF = 407.1 L/kg wet-wt)

Arnot-Gobas BCF model (Whole body Primary Biotransformation Rate estimate for fish), for C7 isomer:

TYPE

NUM

LOG BIOTRANSFORMATION FRAGMENT DESCRIPTION

COEFF

VALUE

Frag

Frag

Frag

Frag

Frag

Frag

L Kow

MolWt

Const

2

1

4

2

4

2

*

*

*

Ester [-C(=O)-O-C]

Carbon with 4 single bonds & no hydrogens

Methyl [-CH3]

-CH2- [linear]

-CH2- [cyclic]

-CH- [cyclic]

Log Kow = 4.46 (user-entered)

Molecular Weight Parameter

Equation Constant

-0.7605

-0.2984

0.2451

0.0242

0.0963

0.0126

0.3073

-1.5211

-0.2984

0.9804

0.0484

0.3850

0.0252

1.3707

-0.6933

-1.5058

RESULT

RESULT

NOTE

Log Bio Half-life (days)

Bio Half-life (days)

Bio Half-life Normalized to 10 g fish at 15°C

-1.2401

0.05753

Biotransformation rate constant:kM (rate constant) = 12.05 / day (10 gram fish).

Arnot-Gobas BCFBAF Methods (including biotransformation rate estimates):

Estimated Log BCF (upper trophic) = 1.399 (BCF = 25.07 L/Kg wet-wt).

Estimated Log BCF (mid trophic) = 1.530 (BCF = 33.86 L/Kg wet-wt).

Estimated Log BCF (lower trophic) = 1.569 (BCF = 37.08 L/Kg wet-wt).

Arnot-Gobas BCFBAF Methods (assuming a biotransformation rate of zero):

Estimated Log BCF (upper trophic) = 3.447 (BCF = 2801 L/Kg wet-wt).

Validity criteria fulfilled:
yes
Conclusions:
The BCF for the C7 isomer of the substance is estimated to be 407 L/Kg wet-wt based on the log Kow value and 37.08 L/kg wet-wt based on Arnot-Gobas method (lower trophic, including biotransformation rate estimates).
Executive summary:

The bioconcentration factor (BCF) of the C7 isomer of the substance was evaluated with BCFBAF model v3.01 from EPI Suite v4.1, which fulfilled all OECD principles. The C7 isomer of the substance is within the domain of the BCFBAF model based on the molecular weight and fragments present in the BCFBAF database.

Based on the biodegradation potential of the substance, it's more relevant to consider the result obtain with Arnot-Gobas Method, including biotransformation rate estimates instead of the result obtain with Arnot-Gobas Method, assuming a biotransformation rate of zero. The BCF for the C7 isomer of the substance is estimated to be 407 L/Kg wet-wt based on the log Kow value and 37.08 L/kg wet-wt based on Arnot-Gobas method (lower trophic, including biotransformation rate estimates).

Description of key information

QSAR, BCFBAF model v3.01 (EPI Suite v4.1), WoE, validity 2:

BCF = 215 L/kg ww for C6 isomer;

BCF = 222 L/kg ww for C7 isomer.

The estimated BCF for C6 isomer is used for key value for chemical safety assessment because it is the main isomer.

Key value for chemical safety assessment

BCF (aquatic species):
215 L/kg ww

Additional information

The bioconcentration factors (BCF) of the registered substance (C6 and C7 isomers) were evaluated with BCFBAF model v3.01 from EPI Suite v4.1, which fulfilled all OECD principles. The substance is within the domain of the BCFBAF model based on the molecular weight and fragments present in the BCFBAF database.

Based on the biodegradation potential of the substance, it's more relevant to consider the result obtain with Arnot-Gobas Method, including biotransformation rate estimates instead of the result obtain with Arnot-Gobas Method, assuming a biotransformation rate of zero.

For the C6 isomer of the substance, the BCF is estimated at 215 L/kg wet-wt, corresponding to the mean of the BCF based on the log Kow value (407 L/kg wet-wt) and the BCF based on Arnot-Gobas method (23.73 L/kg wet-wt, lower trophic including biotransformation rate estimates).

For the C7 isomer of the substance, the BCF is estimated at 222 L/kg wet-wt, corresponding to the mean of the BCF based on the log Kow value (407 L/kg wet-wt) and the BCF based on Arnot-Gobas method (37.08 L/Kg wet-wt, lower trophic including biotransformation rate estimates).