2,6,10-Trimethyldodecane (Farnesane)

Bioaccumulation: aquatic / sediment

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

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:

An in silico study has been performed to evaluate the BIOCONCENTRATION FACTOR (LOG BCF) of the test item using several Quantitative Structure-Property Relationship (QSPR) models. These models have been checked to be compliant with the OECD recommendations for QSAR modeling. Episuite and the BCFBAF models are well documented and commonly used QSARs for predicting the bioaccumulation potential of chemicals.
Log KOW is considered to be the key parameter explaining the transfer from water to the lipidic phase of the fish cell. The assumption is that bioconcentration is a thermodynamically driven partitioning process between water and the lipid phase of the exposed organism, and therefore can be modeled using n-octanol as a surrogate for biological lipids.
Information on the mechanistic basis of the model are in Section 13.2

Qualifier:

no guideline required

Principles of method if other than guideline:

- Model name: BCFBAF model (BCF)
- Model version: v3.01
- Reference to QMRF:
QMRF Identifier (title): QSAR Model Reporting Format (QMRF) for BCFBAF model (BCF) v3.01 using EPI Suite v4.11
- Predicted value (model result): log BCF of the test item was predicted as 2.69.
- Predicted value (comments): BCF of the test item is equal to 495 L/kg (wet weight).
- Input for prediction: Log KOW of the test item.
- Descriptor values: Log KOW of the test item was predicted to be 8.7 (KREATiS, 2021).

Specific details on test material used for the study:

IUPAC name (synonym) 2,6,10-TRIMETHYLDODECANE (FARNESANE)
SMILES CCC(C)CCCC(C)CCCC(C)C
Substance type monoconstituent
CAS-No. 3891-98-3
EC-No. 622-542-2
Molecular formula C15H32
Molecular weight 212.41 g/mol
Description liquid
log KOW 8.7 (KREATiS, 2021a)
Water Solubility at 25°C 2.26E-04 mg/L (KREATiS, 2021b)

Key result

Type:

BCF

Value:

495 L/kg

Basis:

whole body w.w.

Calculation basis:

other: Quantitative Structure-Property Relationship (QSPR) models were used to calculate the BIOCONCENTRATION FACTOR (LOG BCF) of the test item.

Remarks:

The prediction of the BCF for the test item took into account the following correction factor: Alkyl chains (8+ CH2 groups) for log Kow 7-10 x1

Conclusions:

The log BCF of the test item was predicted as 2.69 (BCF = 495 L/kg (wet weight)).
No uncertainty measure is given for the prediction.
The test item falls within the applicability domain of the model and was therefore reliably predicted without restriction for its log BCF.

Executive summary:

Quantitative Structure-Property Relationship (QSPR) models were used to calculate the BIOCONCENTRATION FACTOR (LOG BCF) of the test item. Only predictions within the applicability domain of the models have been considered for this study. In case of multiple predictions, aconsensus value based on the arithmetic mean has been calculated.

Reference 2

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

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:

An in silico study has been performed to evaluate the BIOCONCENTRATION FACTOR (LOG BCF) of the test item using several Quantitative Structure-Property Relationship (QSPR) models. These models have been checked to be compliant with the OECD recommendations for QSAR modeling. They all predict the endpoint value which would be expected when testing the substance under experimental conditions in a laboratory following the Guideline for Testing of Chemicals No. 305, "Bioaccumulation in Fish: Aqueous and Dietary Exposure". The criterion predicted was the bioconcentration factor (BCF) in L/kg expressed in his logarithm.
The method is based on the lethal/critical body burden (L/CBB) concept which states that:
BCF (L/Kg) = LBB (Mol/Kg) / LC50 (Mol/L)
BCF (L/Kg) = CBB (Mol/Kg) / EC10 (Mol/L)
This methodology has been validated separately for the three phases using BCF data from the cited sources and is considered to be suitably conservative, constituting a scientifically justifiable explanation and reasonably conservative predictor of the BCF validation set.
Information on the mechanistic basis of the mode: are in Section 13.2

Qualifier:

no guideline required

Principles of method if other than guideline:

- Model name: iSafeRat® fishBCF
- Model version: V1.0
- Reference to QMRF:
QMRF Identifier (title): QSAR Model Reporting Format (QMRF) for iSafeRat® fishBCF v1.0
- Predicted value (model result): log BCF of the test item was predicted as 2.5.
- Predicted value (comments): BCF of the test item is equal to 3.25E+02 L/kg (wet weight).
- Input for prediction: Subcooled Liquid Water Solubility (SLWS) of the test item.
- Descriptor values: For liquids at 25°C, the SLWS is directly equal to the value of the Water Solubility of the test item.
Water Solubility of the test item was predicted to be 2.26E-04 mg/L or -8.973 in log10 (mol/L) at 25°C (KREATiS, 2021a) using the log KOW value as the input.
Log KOW of the test item was predicted to be 8.7 at 25°C (KREATiS, 2021b).
Therefore, the Subcooled Liquid Water Solubility of the test item used as the input was
2.26E-04 mg/L or -8.973 in log10 (mol/L).

Specific details on test material used for the study:

IUPAC name (synonym) 2,6,10-TRIMETHYLDODECANE (FARNESANE)
SMILES CCC(C)CCCC(C)CCCC(C)C
Substance type monoconstituent
CAS-No. 3891-98-3
EC-No. 622-542-2
Molecular formula C15H32
Molecular weight 212.41 g/mol
Description liquid
log KOW 8.7 (KREATiS, 2021a)
Water Solubility at 25°C 2.26E-04 mg/L (KREATiS, 2021b)

Key result

Type:

BCF

Value:

ca. 325 L/kg

Basis:

whole body w.w.

Calculation basis:

other: Quantitative Structure-Property Relationship (QSPR) models were used to calculate the BIOCONCENTRATION FACTOR (LOG BCF) of the test item.

Conclusions:

The log BCF of the test item was predicted as 2.5 (BCF = 3.25E+02 L/kg (wet weight)).
No uncertainty measure is given for the prediction.
The test item falls within the applicability domain of the model and was therefore reliably predicted without restriction for its log BCF.

Executive summary:

Quantitative Structure-Property Relationship (QSPR) models were used to calculate the BIOCONCENTRATION FACTOR (LOG BCF) of the test item. Only predictions within the applicability domain of the models have been considered for this study. In case of multiple predictions, aconsensus value based on the arithmetic mean has been calculated.

Reference 3

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 test item falls within the global applicability domain of the model, but not for the local applicability domain. Therefore, the log BCF prediction for the test item is considered as reliable with restrictions.

Justification for type of information:

An in silico study has been performed to evaluate the BIOCONCENTRATION FACTOR (LOG BCF) of the test item using several Quantitative Structure-Property Relationship (QSPR) models. These models have been checked to be compliant with the OECD recommendations for QSAR modeling. They all predict the endpoint value which would be expected when testing the substance under experimental conditions in a laboratory following the Guideline for Testing of Chemicals No. 305, "Bioaccumulation in Fish: Aqueous and Dietary Exposure". The criterion predicted was the bioconcentration factor (BCF) in L/kg expressed in his logarithm.
The model descriptors were selected statistically but they can also be partially mechanistically interpreted a posteriori. Several publications reported a general bilinear correlation pattern between BCF and log KOW. In this model, several descriptors related to lipophilicity were used. They are calculated with different methods and provide different information (XLogP, CrippenLogP and ALogP). Since the number of H-bond acceptor atoms explains the tendency of polar chemicals towards aquatic partitioning, two related descriptors were found (nHBAcc, LipinskiFailures). The number of acidic groups (nAcid) is also a descriptor that encodes information about the partitioning of a chemical between the organic and water phases. Factors that increase intermolecular interactions (hydrogen bonding and polarity) lower the bioconcentration factor by making molecules remain in the aqueous phase, or cause binding to membranes and thereby hinder penetration into the organism.
Electronic properties (polarizability and electronegativity) are of high significance to BCF modelling. Such information is encoded in these descriptors (minsC, naasC and ATSC1s). van de Waals volume, here encoded in (ATSC0v) was shown to be of utility to BCF modelling.
Information on the mechanistic basis of the model are in Section 13.2

Qualifier:

no guideline required

Principles of method if other than guideline:

- Model name: BCF model
- Model version: v2.6
- Reference to QMRF
QMRF Identifier (title):QSAR Model Reporting Format (QMRF) for BCF model using OPERA 2.6
- Predicted value (model result): log BCF of the test item was predicted as 3.148.
- Predicted value (comments): BCF of the test item is equal to 1406 L/kg (wet weight).
- Input for prediction: None.
- Descriptor values:
- XLogP, Unitless, An estimate of LogP
XlogP = 8.692
- CrippenLogP, Unitless, CrippenDescriptor related to LogP calculation
CrippenLogP = 5.665
- nHBAcc, Unitless, PaDEL H-Bond Acceptor Count Descriptor. Number of hydrogen bond acceptors (using CDK HBondAcceptorCountDescriptor algorithm)
nHBAcc = 0
- minsCl, Unitless, Atom type electrotopological state: Minimum atom-type E-State: -Cl
minsCl = 0
- LipinskiFailures, Unitless, Number failures of the Lipinski's Rule Of 5.
LipinskiFailures = 1
- ALogP, Unitless, Ghose-Crippen LogKow
AlogP = 1.049
- naasC, Unitless, Atom type electrotopological state: Count of atom-type E-State: :C:
naasC = 0
- nAcid, Unitless, Number of acidic groups. The list of acidic groups is defined by these SMARTS "$([O;H1]-[C,S,P]=O)", "$([*;-;!$(*~[*;+])])", "$([NH](S(=O)=O)C(F)(F)F)", and "$(n1nnnc1)" originally presented in JOELib
nAcid = 0
- ATSC0v, Unitless, Centered Broto-Moreau autocorrelation - lag 0 / weighted by van der Waals volumes
ATSC0v = 2299.174
- ATSC1s, Unitless, Centered Broto-Moreau autocorrelation - lag 1 / weighted by I-state
ATSC1s = -2.135

Specific details on test material used for the study:

IUPAC name (synonym) 2,6,10-TRIMETHYLDODECANE (FARNESANE)
SMILES CCC(C)CCCC(C)CCCC(C)C
Substance type monoconstituent
CAS-No. 3891-98-3
EC-No. 622-542-2
Molecular formula C15H32
Molecular weight 212.41 g/mol
Description liquid
log KOW 8.7 (KREATiS, 2021a)
Water Solubility at 25°C 2.26E-04 mg/L (KREATiS, 2021b)

Key result

Type:

BCF

Value:

1 406 L/kg

Basis:

whole body w.w.

Calculation basis:

other: Quantitative Structure-Property Relationship (QSPR) models were used to calculate the BIOCONCENTRATION FACTOR (LOG BCF) of the test item.

Conclusions:

The log BCF of the test item was predicted as 3.148 (BCF = 1406 L/kg (wet weight)).
No uncertainty measure is given for the prediction.

The test item falls within the global applicability domain of the model, but not for the local applicability domain. Therefore, the log BCF prediction for the test item is considered as reliable with restrictions.

Executive summary:

Quantitative Structure-Property Relationship (QSPR) models were used to calculate the BIOCONCENTRATION FACTOR (LOG BCF) of the test item. Only predictions within the applicability domain of the models have been considered for this study. In case of multiple predictions, aconsensus value based on the arithmetic mean has been calculated.

Reference 4

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 and falling into its applicability domain, with adequate and reliable documentation / justification

Remarks:

The test item falls within the applicability domain of the model and was therefore reliably predicted for its log BCF. However, the prediction accuracy (MAE) for the most similar chemicals to the test item was lower than for the entire training set. Therefore, even if the prediction is considered as reliable, some restrictions about accuracy must be taken into account.

Justification for type of information:

An in silico study has been performed to evaluate the BIOCONCENTRATION FACTOR (LOG BCF) of the test item using several Quantitative Structure-Property Relationship (QSPR) models. These models have been checked to be compliant with the OECD recommendations for QSAR modeling. They all predict the endpoint value which would be expected when testing the substance under experimental conditions in a laboratory following the Guideline for Testing of Chemicals No. 305, "Bioaccumulation in Fish: Aqueous and Dietary Exposure". The criterion predicted was the bioconcentration factor (BCF) in L/kg expressed in his logarithm.

Qualifier:

no guideline required

Principles of method if other than guideline:

- Model name: BCF model (Group Contribution)
- Model version: v5.1.1
- Reference to QMRF:
QMRF Identifier (title): QSAR Model Reporting Format (QMRF) for BCF model (Group Contribution) using TEST v5.1.1
- Predicted value (model result): log BCF of the test item was predicted as 2.88.
- Predicted value (comments): BCF of the test item is equal to 758 L/kg (wet weight).
- Input for prediction: None.

Specific details on test material used for the study:

IUPAC name (synonym) 2,6,10-TRIMETHYLDODECANE (FARNESANE)
SMILES CCC(C)CCCC(C)CCCC(C)C
Substance type monoconstituent
CAS-No. 3891-98-3
EC-No. 622-542-2
Molecular formula C15H32
Molecular weight 212.41 g/mol
Description liquid
log KOW 8.7 (KREATiS, 2021a)
Water Solubility at 25°C 2.26E-04 mg/L (KREATiS, 2021b)

Key result

Type:

BCF

Value:

758 L/kg

Basis:

whole body w.w.

Calculation basis:

other: Quantitative Structure-Property Relationship (QSPR) models were used to calculate the BIOCONCENTRATION FACTOR (LOG BCF) of the test item.

Conclusions:

The log BCF of the test item was predicted as 2.88 (BCF = 758 L/kg (wet weight)).
Prediction interval, defined as 90% confidence interval (α = 0.01): 1.54 – 4.22

The test item falls within the applicability domain of the model and was therefore reliably predicted for its log BCF. However, the prediction accuracy (MAE) for the most similar chemicals to the test item was lower than for the entire training set. Therefore, even if the prediction is considered as reliable, some restrictions about accuracy must be taken into account.

Executive summary:

Quantitative Structure-Property Relationship (QSPR) models were used to calculate the BIOCONCENTRATION FACTOR (LOG BCF) of the test item. Only predictions within the applicability domain of the models have been considered for this study. In case of multiple predictions, aconsensus value based on the arithmetic mean has been calculated.

Reference 5

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

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 test item falls within the applicability domain of the model and was therefore reliably predicted for its log BCF.

Justification for type of information:

An in silico study has been performed to evaluate the BIOCONCENTRATION FACTOR (LOG BCF) of the test item using several Quantitative Structure-Property Relationship (QSPR) models. These models have been checked to be compliant with the OECD recommendations for QSAR modeling. They all predict the endpoint value which would be expected when testing the substance under experimental conditions in a laboratory following the Guideline for Testing of Chemicals No. 305, "Bioaccumulation in Fish: Aqueous and Dietary Exposure". The criterion predicted was the bioconcentration factor (BCF) in L/kg expressed in his logarithm.

Qualifier:

no guideline required

Principles of method if other than guideline:

- Model name: BCF model (Hierarchical Clustering)
- Model version: v5.1.1
- Reference to QMRF:
QMRF Identifier (title): QSAR Model Reporting Format (QMRF) for BCF model (Hierarchical Clustering) using TEST v5.1.1
- Predicted value (model result): llog BCF of the test item was predicted as 2.64.
- Predicted value (comments): BCF of the test item is equal to 433 L/kg (wet weight).
- Input for prediction: None.

Specific details on test material used for the study:

IUPAC name (synonym) 2,6,10-TRIMETHYLDODECANE (FARNESANE)
SMILES CCC(C)CCCC(C)CCCC(C)C
Substance type monoconstituent
CAS-No. 3891-98-3
EC-No. 622-542-2
Molecular formula C15H32
Molecular weight 212.41 g/mol
Description liquid
log KOW 8.7 (KREATiS, 2021a)
Water Solubility at 25°C 2.26E-04 mg/L (KREATiS, 2021b)

Key result

Type:

BCF

Value:

433 L/kg

Basis:

whole body w.w.

Calculation basis:

other: Quantitative Structure-Property Relationship (QSPR) models were used to calculate the BIOCONCENTRATION FACTOR (LOG BCF) of the test item.

Conclusions:

The log BCF of the test item was predicted as 2.64 (BCF = 433 L/kg (wet weight)).
Prediction interval, defined as 90% confidence interval (α = 0.01): 2.55 – 2.72

The test item falls within the applicability domain of the model and was therefore reliably predicted for its log BCF.

Executive summary:

Quantitative Structure-Property Relationship (QSPR) models were used to calculate the BIOCONCENTRATION FACTOR (LOG BCF) of the test item. Only predictions within the applicability domain of the models have been considered for this study. In case of multiple predictions, aconsensus value based on the arithmetic mean has been calculated.

Reference 6

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

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 test item falls within the applicability domain of the model and was therefore reliably predicted for its log BCF.

Justification for type of information:

An in silico study has been performed to evaluate the BIOCONCENTRATION FACTOR (LOG BCF) of the test item using several Quantitative Structure-Property Relationship (QSPR) models. These models have been checked to be compliant with the OECD recommendations for QSAR modeling. They all predict the endpoint value which would be expected when testing the substance under experimental conditions in a laboratory following the Guideline for Testing of Chemicals No. 305, "Bioaccumulation in Fish: Aqueous and Dietary Exposure". The criterion predicted was the bioconcentration factor (BCF) in L/kg expressed in his logarithm.

Qualifier:

no guideline required

Principles of method if other than guideline:

- Model name: BCF model (Nearest Neighbor)
- Model version: v5.1.1
- Reference to QMRF:
QMRF Identifier (title): QSAR Model Reporting Format (QMRF) for BCF model (Nearest Neighbor) using TEST v5.1.1
- Predicted value (model result): log BCF of the test item was predicted as 3.28.
- Predicted value (comments): BCF of the test item is equal to 1905 L/kg (wet weight).
- Input for prediction: None.

Specific details on test material used for the study:

IUPAC name (synonym) 2,6,10-TRIMETHYLDODECANE (FARNESANE)
SMILES CCC(C)CCCC(C)CCCC(C)C
Substance type monoconstituent
CAS-No. 3891-98-3
EC-No. 622-542-2
Molecular formula C15H32
Molecular weight 212.41 g/mol
Description liquid
log KOW 8.7 (KREATiS, 2021a)
Water Solubility at 25°C 2.26E-04 mg/L (KREATiS, 2021b)

Key result

Type:

BCF

Value:

1 905 L/kg

Basis:

whole body w.w.

Calculation basis:

other: Quantitative Structure-Property Relationship (QSPR) models were used to calculate the BIOCONCENTRATION FACTOR (LOG BCF) of the test item.

Conclusions:

The log BCF of the test item was predicted as 3.28 (BCF = 1905 L/kg (wet weight)).
No uncertainty measure is given for the prediction.

The test item falls within the applicability domain of the model and was therefore reliably predicted for its log BCF.

Executive summary:

Quantitative Structure-Property Relationship (QSPR) models were used to calculate the BIOCONCENTRATION FACTOR (LOG BCF) of the test item. Only predictions within the applicability domain of the models have been considered for this study. In case of multiple predictions, aconsensus value based on the arithmetic mean has been calculated.

Reference 7

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 and falling into its applicability domain, with adequate and reliable documentation / justification

Remarks:

The test item falls within the applicability domain of the model and was therefore reliably predicted for its log BCF. However, the prediction accuracy (MAE) for the most similar chemicals to the test item was lower than for the entire training set. Therefore, even if the prediction is considered as reliable, some restrictions about accuracy must be taken into account.

Justification for type of information:

An in silico study has been performed to evaluate the BIOCONCENTRATION FACTOR (LOG BCF) of the test item using several Quantitative Structure-Property Relationship (QSPR) models. These models have been checked to be compliant with the OECD recommendations for QSAR modeling. They all predict the endpoint value which would be expected when testing the substance under experimental conditions in a laboratory following the Guideline for Testing of Chemicals No. 305, "Bioaccumulation in Fish: Aqueous and Dietary Exposure". The criterion predicted was the bioconcentration factor (BCF) in L/kg expressed in his logarithm.

Qualifier:

no guideline required

Principles of method if other than guideline:

- Model name: BCF model (Single Model)
- Model version: v5.1.1
- Reference to QMRF:
QMRF Identifier (title): QMRF Identifier (title):QSAR Model Reporting Format (QMRF) for BCF model (Single Model) using TEST v5.1.1
- Predicted value (model result): log BCF of the test item was predicted as 3.33.
- Predicted value (comments): BCF of the test item is equal to 2133 L/kg (wet weight).
- Input for prediction: None.

Specific details on test material used for the study:

IUPAC name (synonym) 2,6,10-TRIMETHYLDODECANE (FARNESANE)
SMILES CCC(C)CCCC(C)CCCC(C)C
Substance type monoconstituent
CAS-No. 3891-98-3
EC-No. 622-542-2
Molecular formula C15H32
Molecular weight 212.41 g/mol
Description liquid
log KOW 8.7 (KREATiS, 2021a)
Water Solubility at 25°C 2.26E-04 mg/L (KREATiS, 2021b)

Key result

Type:

BCF

Value:

2 133 L/kg

Basis:

whole body w.w.

Calculation basis:

other: Quantitative Structure-Property Relationship (QSPR) models were used to calculate the BIOCONCENTRATION FACTOR (LOG BCF) of the test item.

Conclusions:

The log BCF of the test item was predicted as 3.33 (BCF = 2133 L/kg (wet weight)).
Prediction interval, defined as 90% confidence interval (α = 0.01): 2.18 – 4.47

The test item falls within the applicability domain of the model and was therefore reliably predicted for its log BCF. However, the prediction accuracy (MAE) for the most similar chemicals to the test item was lower than for the entire training set. Therefore, even if the prediction is considered as reliable, some restrictions about accuracy must be taken into account.

Executive summary:

Quantitative Structure-Property Relationship (QSPR) models were used to calculate the BIOCONCENTRATION FACTOR (LOG BCF) of the test item. Only predictions within the applicability domain of the models have been considered for this study. In case of multiple predictions, aconsensus value based on the arithmetic mean has been calculated.

Reference 8

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

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 test item falls within the applicability domain of the model and was therefore reliably predicted for its log BCF.

Justification for type of information:

An in silico study has been performed to evaluate the BIOCONCENTRATION FACTOR (LOG BCF) of the test item using several Quantitative Structure-Property Relationship (QSPR) models. These models have been checked to be compliant with the OECD recommendations for QSAR modeling. They all predict the endpoint value which would be expected when testing the substance under experimental conditions in a laboratory following the Guideline for Testing of Chemicals No. 305, "Bioaccumulation in Fish: Aqueous and Dietary Exposure". The criterion predicted was the bioconcentration factor (BCF) in L/kg expressed in his logarithm.
The model largely relies on log P (Log KOW), which typically is the main descriptor used for BCF. Corrections are applied to balance the use of the specific log P calculator, MLogP. Indeed, this particular descriptor gives good results when chemicals contain carbon, nitrogen and oxygen, but it may be less accurate in case of compounds with other atoms, like Cl and P.

Qualifier:

no guideline required

Principles of method if other than guideline:

- Model name: BCF model (CAESAR)
- Model version: v2.1.14
- Reference to QMRF:
QMRF Identifier (title): QSAR Model Reporting Format (QMRF) for BCF model (CAESAR) v2.1.14 using VEGA v1.1.5
- Predicted value (model result): log BCF of the test item was predicted as 2.86.
- Predicted value (comments):BCF of the test item is equal to 727 L/kg (wet weight).
- Input for prediction: None.
- Descriptor values:
- Moriguchi octanol-water partition coefficient (MlogP).
- Moran autocorrelation of lag 5, weighted by atomic van der Waals volumes (MATS5V): molecular descriptor calculated from the molecular graph by summing the products of atom weights of the terminal atoms of all paths of the considered path length (the lag).
- Number of chlorine atoms (Cl-089), Cl attached to carbon (sp2).
- Second highest eigenvalue of Burden matrix, weighted by atomic polarizabilities (BEHp2).
- Geary autocorrelation of lag 5, weighted by atomic van der Waals volumes (GATS5V): molecular descriptor calculated from the molecular graph by summing the products of atom weights of the terminal atoms of all paths of the considered path length (the lag).
- Solvation connectivity index chi-0 (XOSolv): molecular descriptor designed for modeling solvation entropy and describing dispersion interactions in solution.
- Sum of all -Cl groups E-state values in molecule (SsCl).
- Absolute eigenvalues sum from electronegativity weighted distance matrix (Aeige).

Specific details on test material used for the study:

IUPAC name (synonym) 2,6,10-TRIMETHYLDODECANE (FARNESANE)
SMILES CCC(C)CCCC(C)CCCC(C)C
Substance type monoconstituent
CAS-No. 3891-98-3
EC-No. 622-542-2
Molecular formula C15H32
Molecular weight 212.41 g/mol
Description liquid
log KOW 8.7 (KREATiS, 2021a)
Water Solubility at 25°C 2.26E-04 mg/L (KREATiS, 2021b)

Key result

Type:

BCF

Value:

727 L/kg

Basis:

whole body w.w.

Calculation basis:

other: Quantitative Structure-Property Relationship (QSPR) models were used to calculate the BIOCONCENTRATION FACTOR (LOG BCF) of the test item.

Conclusions:

The log BCF of the test item was predicted as 2.86 (BCF = 727 L/kg (wet weight)).
No uncertainty measure is given for the prediction.

The test item falls within the applicability domain of the model and was therefore reliably predicted for its log BCF.

Executive summary:

Quantitative Structure-Property Relationship (QSPR) models were used to calculate the BIOCONCENTRATION FACTOR (LOG BCF) of the test item. Only predictions within the applicability domain of the models have been considered for this study. In case of multiple predictions, aconsensus value based on the arithmetic mean has been calculated.

Reference 9

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

other: test item falls outside the applicability domain

Rationale for reliability incl. deficiencies:

other: test item falls outside the applicability domain

Remarks:

The test item falls outside the applicability domain of the model because: - Some similar molecules found in the training set have experimental values that disagree with the predicted value. - The maximum error in prediction of similar molecules found in the training set has a high value, considering the experimental variability. Therefore, the prediction for the log BCF of the test item is considered as unreliable.

Justification for type of information:

An in silico study has been performed to evaluate the BIOCONCENTRATION FACTOR (LOG BCF) of the test item using several Quantitative Structure-Property Relationship (QSPR) models. These models have been checked to be compliant with the OECD recommendations for QSAR modeling. They all predict the endpoint value which would be expected when testing the substance under experimental conditions in a laboratory following the Guideline for Testing of Chemicals No. 305, "Bioaccumulation in Fish: Aqueous and Dietary Exposure". The criterion predicted was the bioconcentration factor (BCF) in L/kg expressed in his logarithm.

Qualifier:

no guideline required

Principles of method if other than guideline:

- Model name: BCF model (kNN/Read-Across)
- Model version: v1.1.0
- Reference to QMRF:
QMRF Identifier (title): QSAR Model Reporting Format (QMRF) for BCF model (kNN/Read-Across) v1.1.0 using VEGA v1.1.5
- Predicted value (model result): log BCF of the test item was predicted as 2.83.
- Predicted value (comments): BCF of the test item is equal to 676 L/kg (wet weight).
- Input for prediction: SMILES of the test item.
- Descriptor values: None.

Specific details on test material used for the study:

IUPAC name (synonym) 2,6,10-TRIMETHYLDODECANE (FARNESANE)
SMILES CCC(C)CCCC(C)CCCC(C)C
Substance type monoconstituent
CAS-No. 3891-98-3
EC-No. 622-542-2
Molecular formula C15H32
Molecular weight 212.41 g/mol
Description liquid
log KOW 8.7 (KREATiS, 2021a)
Water Solubility at 25°C 2.26E-04 mg/L (KREATiS, 2021b)

Key result

Type:

BCF

Value:

676 L/kg

Basis:

whole body w.w.

Calculation basis:

other: Quantitative Structure-Property Relationship (QSPR) models were used to calculate the BIOCONCENTRATION FACTOR (LOG BCF) of the test item.

Conclusions:

The log BCF of the test item was predicted as 2.83 (BCF = 676 L/kg (wet weight)).
No uncertainty measure is given for the prediction.

The test item falls outside the applicability domain of the model because:
- Some similar molecules found in the training set have experimental values that disagree with the predicted value.
- The maximum error in prediction of similar molecules found in the training set has a high value, considering the experimental variability.
Therefore, the prediction for the log BCF of the test item is considered as unreliable.

Executive summary:

Quantitative Structure-Property Relationship (QSPR) models were used to calculate the BIOCONCENTRATION FACTOR (LOG BCF) of the test item. Only predictions within the applicability domain of the models have been considered for this study. In case of multiple predictions, aconsensus value based on the arithmetic mean has been calculated.

Reference 10

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 test item falls within the applicability domain of the model, except for the structural domain because: Some similar molecules found in the training set have experimental values that disagree with the predicted value. Furthermore, the reliability of log KOW value used by the model is not optimal. Therefore, the prediction for the log BCF of the test item is considered as reliable with some restrictions.

Justification for type of information:

An in silico study has been performed to evaluate the BIOCONCENTRATION FACTOR (LOG BCF) of the test item using several Quantitative Structure-Property Relationship (QSPR) models. These models have been checked to be compliant with the OECD recommendations for QSAR modeling. They all predict the endpoint value which would be expected when testing the substance under experimental conditions in a laboratory following the Guideline for Testing of Chemicals No. 305, "Bioaccumulation in Fish: Aqueous and Dietary Exposure". The criterion predicted was the bioconcentration factor (BCF) in L/kg expressed in his logarithm.
Log KOW is considered to be the key parameter explaining the transfer from water to the lipidic phase of the fish cell. The assumption is that bioconcentration is a thermodynamically driven partitioning process between water and the lipid phase of the exposed organism, and therefore can be modelled using n-octanol as a surrogate for biological lipids.
Information on the mechanistic basis of the model are in Section 13.2

Qualifier:

no guideline required

Principles of method if other than guideline:

- Model name: BCF model (Meylan)
- Model version: v1.0.3
- Reference to QMRF:
QMRF Identifier (title): QSAR Model Reporting Format (QMRF) for BCF model (Meylan) v1.0.3 using VEGA v1.1.5
- Predicted value (model result): log BCF of the test item was predicted as 3.29.
- Predicted value (comments): BCF of the test item is equal to 1944 L/kg (wet weight).
- Input for prediction: None.
- Descriptor values: Log KOW of the test item was predicted to be 7.49 by the software itself.

Specific details on test material used for the study:

IUPAC name (synonym) 2,6,10-TRIMETHYLDODECANE (FARNESANE)
SMILES CCC(C)CCCC(C)CCCC(C)C
Substance type monoconstituent
CAS-No. 3891-98-3
EC-No. 622-542-2
Molecular formula C15H32
Molecular weight 212.41 g/mol
Description liquid
log KOW 8.7 (KREATiS, 2021a)
Water Solubility at 25°C 2.26E-04 mg/L (KREATiS, 2021b)

Key result

Type:

BCF

Value:

1 944 L/kg

Basis:

whole body w.w.

Calculation basis:

other: Quantitative Structure-Property Relationship (QSPR) models were used to calculate the BIOCONCENTRATION FACTOR (LOG BCF) of the test item.

Remarks:

The prediction of the BCF for the test item took into account the following correction factor: Alkyl chains (8+ CH2 groups) for log Kow 7-10 x1

Conclusions:

The log BCF of the test item was predicted as 3.29 (BCF = 1944 L/kg (wet weight)).
No uncertainty measure is given for the prediction.
The test item falls within the applicability domain of the model, except for the structural domain because:
Some similar molecules found in the training set have experimental values that disagree with the predicted value.
Furthermore, the reliability of log KOW value used by the model is not optimal. Therefore, the prediction for the log BCF of the test item is considered as reliable with some restrictions.

Executive summary:

Quantitative Structure-Property Relationship (QSPR) models were used to calculate the BIOCONCENTRATION FACTOR (LOG BCF) of the test item. Only predictions within the applicability domain of the models have been considered for this study. In case of multiple predictions, aconsensus value based on the arithmetic mean has been calculated.

Description of key information

An in silico study has been performed to evaluate the BIOCONCENTRATION FACTOR (LOG BCF) of the test item using several Quantitative Structure-Property Relationship (QSPR) models. These models have been checked to be compliant with the OECD recommendations for QSAR modeling. They all predict the endpoint value which would be expected when testing the substance under experimental conditions in a laboratory following the Guideline for Testing of Chemicals No. 305, "Bioaccumulation in Fish: Aqueous and Dietary Exposure". The criterion predicted was the bioconcentration factor (BCF) in L/kg expressed in his logarithm.

 

The BIOCONCENTRATION FACTOR (LOG BCF) values were determined using the following QSPR models:

•       iSafeRat® fishBCF v1.0;

•       BCFBAF model (BCF) v3.01 from EPI Suite v4.11 software;

•       BCF model from OPERA v2.6 software;

•       BCF model (Hierarchical Clustering) from TEST v5.1.1 software;

•       BCF model (Single Model) from TEST v5.1.1 software;

•       BCF model (Group Contribution) from TEST v5.1.1 software;

•       BCF model (Nearest Neighbor) from TEST v5.1.1 software;

•       BCF model (CAESAR) v2.1.14 from VEGA v1.1.5 software;

•       BCF model (kNN/Read-Across) v1.1.0 from VEGA v1.1.5 software;

•       BCF model (Meylan) v1.0.3 from VEGA v1.1.5 software.

For all of these models, the test item has been verified to be, at least partially, within the applicability domain.

The mean BCF was determined as 1000 with a min of 158 and a max of 2138. Only one model out of the 9 within the applicability domain predicted a BCF >2000. Using the consensus approach, the substance is considered to have a BCF of 1000 and to be below the B criterion used in PBT assessment of 2000 L/Kg.

Additional information

Quantitative Structure-Property Relationship (QSPR) models were used to calculate the BIOCONCENTRATION FACTOR (LOG BCF) of the test item. Only predictions within the applicability domain of the models have been considered for this study. In case of multiple predictions, a consensus value based on the arithmetic mean has been calculated.

For the BCF model (kNN/Read-Across) v1.1.0 from VEGA v1.1.5 software, the test item falls outside the applicability domain. Therefore it was not considered for this study.

The BIOCONCENTRATION FACTOR (LOG BCF) value of the test item were determined as: 3.0

The mean BCF was determined as 1000 with a min of 158 and a max of 2138. Only one model out of the 9 within the applicability domain predicted a BCF >2000. Using the consensus approach, the substance is considered to have a BCF of 1000 and to be below the B criterion used in PBT assessment of 2000 L/Kg.