Registration Dossier

Environmental fate & pathways

Bioaccumulation: aquatic / sediment

Currently viewing:

Administrative data

Link to relevant study record(s)

Referenceopen allclose all

Endpoint:
bioaccumulation: aquatic / sediment
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Study period:
April 19, 2012
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Estimation method using accepted and valid (Q)SPR method.
Justification for type of information:
QSAR prediction: migrated from IUCLID 5.6
Guideline:
other: ECHA Guidance on information requirements and chemical safety assessment - Chapter R.06: QSARs and grouping of chemicals - May2008
Principles of method if other than guideline:
The BCFBAF program estimates the Bioconcentration Factor (BCF) of an organic compound using the compound's log octanol-water partition coefficient (Kow).
The original estimation methodology used by the original BCFWIN program is described in a document prepared for the U.S. Environmental Protection Agency (Meylan et al., 1997). The estimation methodology was then published in journal article (Meylan et al, 1999).
BCFBAF has been expanded to include estimation of the Biotransformation Rate (kM) in fish and estimation of Bioaccumulation Factor (BAF) by the Arnot-Gobas method (Arnot and Gobas, 2003.
Details on estimation of bioconcentration:
BASIS INFORMATION
- Measured logPow

BASIS FOR CALCULATION OF BCF
- Estimation software: EPIWIN v.4.1, part BCFBAF v.3.01. (2011)
- Result based on measured log Pow of: 9.3
Type:
BCF
Value:
251 L/kg
Basis:
whole body w.w.
Type:
BAF
Value:
1.14 L/kg
Basis:
whole body w.w.
Calculation basis:
steady state
Remarks on result:
other: upper trophic - including biotransformation rate estimates
Details on kinetic parameters:
- Primary biotransformation rate constant (kM): 3.064 /day (10 gram fish)

--------------------------- BCFBAF v3.01 ---------------------------

Compound Being Estimated:

SMILES: O=C(OCCCCCCCC)c1cc(ccc1C(=O)OCCCCCCCC)C(=O)OCCCCCCCC

CHEM: trioctyl benzene-1,2,4-tricarboxylate

MOL FOR: C33 H54 O6

MOL WT: 546.79

Summary Results:

Log BCF (regression-based estimate): 2.40 (BCF = 251 L/kg wet-wt)

Biotransformation Half-Life (days): 0.226 (normalized to 10 g fish)

Log BAF (Arnot-Gobas upper trophic): 0.06 (BAF = 1.14 L/kg wet-wt)

=============================

BCF (Bioconcentration Factor):

=============================

Log Kow (estimated) : 11.81

Log Kow (experimental): not available from database

Log Kow used by BCF estimates: 9.30 (user entered)

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 = 2.400 (BCF = 251.5 L/kg wet-wt)

=============================================================

Whole Body Primary Biotransformation Rate Estimate for Fish:

=============================================================

TYPE

 NUM

 LOG BIOTRANSFORMATION FRAGMENT DESCRIPTION

 COEFF 

 VALUE 

Frag

 3 

 Linear C4 terminal chain [CCC-CH3]      

 0.0341

 0.1024

Frag

 3 

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

 -0.7605

 -2.2816

Frag

 3 

 Aromatic-H

 0.2664

 0.7991

Frag

 3 

 Methyl [-CH3]

 0.2451

 0.7353

Frag

 21 

 -CH2- [linear]

 0.0242

 0.5079

Frag

 1 

 Benzene

 -0.4277

 -0.4277

L Kow

 * 

 Log Kow =  9.30 (user-entered  )       

 0.3073

 2.8583

MolWt

 * 

 Molecular Weight Parameter               

        

 -1.4022

Const

 * 

 Equation Constant                        

        

 -1.5058

 RESULT  

       LOG Bio Half-Life (days)

 -0.6455

 RESULT  

           Bio Half-Life (days)

 0.2262

 NOTE    

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

Biotransformation Rate Constant:

kM (Rate Constant): 3.064 /day (10 gram fish)

kM (Rate Constant): 1.723 /day (100 gram fish)

kM (Rate Constant): 0.969 /day (1 kg fish)

kM (Rate Constant): 0.5449 /day (10 kg fish)

Arnot-Gobas BCF & BAF Methods (including biotransformation rate estimates):

Estimated Log BCF (upper trophic) = 0.048 (BCF = 1.118 L/kg wet-wt)

Estimated Log BAF (upper trophic) = 0.058 (BAF = 1.143 L/kg wet-wt)

Estimated Log BCF (mid trophic) = 0.094 (BCF = 1.241 L/kg wet-wt)

Estimated Log BAF (mid trophic) = 0.492 (BAF = 3.103 L/kg wet-wt)

Estimated Log BCF (lower trophic) = 0.108 (BCF = 1.281 L/kg wet-wt)

Estimated Log BAF (lower trophic) = 1.299 (BAF = 19.92 L/kg wet-wt)

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

Estimated Log BCF (upper trophic) = 2.592 (BCF = 390.6 L/kg wet-wt)

Estimated Log BAF (upper trophic) = 6.288 (BAF = 1.942e+006 L/kg wet-wt)

Validity criteria fulfilled:
yes
Conclusions:
Calculated BCF is: 251 L/kg wet weight
Calculated BAF is: 1.14 L/kg wet weight
Executive summary:

The BCF and BAF of the substance were estimated using the software BCFBAF v.3.01 to give respectively values of 251 L/kg ww and 1.14 L/kg ww.

The Bio Half-Life was estimated to be: 0.23 days (normalized to 10 g fish at 15 deg C).

The primary biotransformation rate constant (kM) was estimated to be: 3.064 /day (10 gram fish).

It is therefore concluded that the potential for bioaccumulation of trioctyl benzene-1,2,4-tricarboxylate (DIPLAST TM 8) is low.

Endpoint:
bioaccumulation in aquatic species: fish
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Study period:
April 19, 2012
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 limited documentation / justification
Justification for type of information:
See the attached justification.
Guideline:
other: ECHA Guidance on information requirements and chemical safety assessment - Chapter R.06: QSARs and grouping of chemicals
Principles of method if other than guideline:
See the justification for type of information.
Details on estimation of bioconcentration:
BASIS INFORMATION
- Measured/calculated log Pow

BASIS FOR CALCULATION OF BCF
- Estimation software: EPIWIN v.4.11, part BCFBAF v.3.01. (2012)
- Result based on measured log Pow of: 9.3
Type:
BCF
Value:
251 L/kg
Basis:
whole body w.w.
Type:
BAF
Value:
1.14 L/kg
Basis:
whole body w.w.
Calculation basis:
steady state
Remarks on result:
other: upper trophic - including biotransformation rate estimates

--------------------------- BCFBAF v3.01 ---------------------------

Compound Being Estimated:

SMILES: O=C(OCCCCCCCC)c1cc(ccc1C(=O)OCCCCCCCC)C(=O)OCCCCCCCC

CHEM: trioctyl benzene-1,2,4-tricarboxylate

MOL FOR: C33 H54 O6

MOL WT: 546.79

 

Summary Results:

 Log BCF(regression-based estimate): 2.40 (BCF = 251 L/kg wet-wt)

 Biotransformation Half-Life (days): 0.226 (normalized to 10 g fish)

 Log BAF(Arnot-Gobas upper trophic): 0.06 (BAF = 1.14 L/kg wet-wt)

 

 

=============================

BCF (Bioconcentration Factor):

=============================

Log Kow (estimated) : 11.81

Log Kow (experimental): not available from database

Log Kow used by BCF estimates: 9.30 (user entered)

 

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 = 2.400 (BCF = 251.5 L/kg wet-wt)

 

 =============================================================

Whole Body Primary Biotransformation Rate Estimate for Fish:

 

TYPE

 NUM

 LOG BIOTRANSFORMATION FRAGMENT DESCRIPTION

 COEFF 

 VALUE 

Frag

 3 

 Linear C4 terminal chain [CCC-CH3]      

 0.0341

 0.1024

Frag

 3 

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

 -0.7605

 -2.2816

Frag

 3 

 Aromatic-H

 0.2664

 0.7991

Frag

 3 

 Methyl [-CH3]

 0.2451

 0.7353

Frag

 21 

 -CH2- [linear]

 0.0242

 0.5079

Frag

 1 

 Benzene

 -0.4277

 -0.4277

L Kow

 * 

 Log Kow =  9.30 (user-entered  )       

 0.3073

 2.8583

MolWt

 * 

 Molecular Weight Parameter               

        

 -1.4022

Const

 * 

 Equation Constant                        

        

 -1.5058

 RESULT  

       LOG Bio Half-Life (days)

 -0.6455

 RESULT  

           Bio Half-Life (days)

 0.2262

 NOTE    

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

 

Biotransformation Rate Constant:

 kM (Rate Constant): 3.064 /day (10 gram fish)

 kM (Rate Constant): 1.723 /day (100 gram fish)

 kM (Rate Constant): 0.969 /day (1 kg fish)

 kM (Rate Constant): 0.5449 /day (10 kg fish)

 

Arnot-Gobas BCF & BAF Methods (including biotransformation rate estimates):

  Estimated Log BCF (upper trophic) = 0.048 (BCF = 1.118 L/kg wet-wt)

  Estimated Log BAF (upper trophic) = 0.058 (BAF = 1.143 L/kg wet-wt)

  Estimated Log BCF (mid trophic)  = 0.094 (BCF = 1.241 L/kg wet-wt)

  Estimated Log BAF (mid trophic)  = 0.492 (BAF = 3.103 L/kg wet-wt)

  Estimated Log BCF (lower trophic) = 0.108 (BCF = 1.281 L/kg wet-wt)

  Estimated Log BAF (lower trophic) = 1.299 (BAF = 19.92 L/kg wet-wt)

 

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

  Estimated Log BCF (upper trophic) = 2.592 (BCF = 390.6 L/kg wet-wt)

  Estimated Log BAF (upper trophic) = 6.288 (BAF = 1.942e+006 L/kg wet-wt)

Validity criteria fulfilled:
yes
Conclusions:
Calculated BCF is: 251 L/kg wet weight
Calculated BAF is: 1.14 L/kg wet weight
Executive summary:

The BCF and BAF of the test material were estimated using the software BCFBAF v.3.01 to give respectively values of 251 L/kg ww and 1.14 L/kg ww.

It is therefore concluded that the potential for bioaccumulation of the test material is low.

Endpoint:
bioaccumulation: aquatic / sediment
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Study period:
January 30, 2015
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Estimation method using accepted and valid (Q)SPR method.
Justification for type of information:
QSAR prediction: migrated from IUCLID 5.6
Guideline:
other: ECHA Guidance on information requirements and chemical safety assessment - Chapter R.06: QSARs and grouping of chemicals - May2008
Principles of method if other than guideline:
SCOPE
T.E.S.T allows the users to estimate the value for several toxicity end points and physical properties (among these the bioconcentration factor) using a variety of (Q)SAR methodologies. The program does not require molecular descriptors from external software packages because they are calculated within the tool.

(Q)SAR PREDICTION METHODOLOGIES
• Hierarchical method
The toxicity for a given query compound is estimated using the weighted average of the predictions from several different models. The different models are obtained by using Ward’s method to divide the training set into a series of structurally similar clusters. A genetic algorithm based technique is used to generate models for each cluster. The models are generated prior to runtime.

• FDA method
The prediction for each test chemical is made using a new model that is fit to the chemicals that are most similar to the test compound. Each model is generated at runtime.

• Single model method
Predictions are made using a multilinear regression model that is fit to the training set (using molecular descriptors as independent variables) using a genetic algorithm based approach. The regression model is generated prior to runtime.

• Group contribution method
Predictions are made using a multilinear regression model that is fit to the training set (using molecular fragment counts as independent variables). The regression model is generated prior to runtime.

• Nearest neighbor method
The predicted toxicity is estimated by taking an average of the three chemicals in the training set that are most similar to the test chemical.

• Consensus method
The predicted toxicity is estimated by taking an average of the predicted toxicities from the above (Q)SAR methods (provided the predictions are within the respective applicability domains).

• Random forest method
The predicted toxicity is estimated using a decision tree which bins a chemical into a certain toxicity score (i.e. positive or negative developmental toxicity) using a set of molecular descriptors as decision variables. The random forest method is currently only available for the developmental toxicity endpoint. The random forest models for the developmental toxicity endpoint were developed by researchers at Mario Negri Institute for Pharmacological Research as part of the CAESAR project (CAESAR 2009).
Details on estimation of bioconcentration:
BASIS INFORMATION
- Data was compiled from several different databases (Dimitrov et al. 2005; Arnot and Gobas 2006; EURAS; Zhao 2008). The final dataset consists of 676 chemicals (after removing salts, mixtures, and ambiguous compounds).

BASIS FOR CALCULATION OF BCF
- Estimation software: T.E.S.T. v.4.1 (2012)
Type:
BCF
Value:
6.03 dimensionless

Predicted Bioconcentration factor at 25 deg C for trioctyl benzene-1,2,4-tricarboxylate from Consensus method

 

Prediction results

Endpoint

Experimental value

Predicted value

Bioaccumulation factor Log10

N/A

0.78

Bioaccumulation factor

N/A

6.03

 

Individual Predictions

Method

Predicted value
Log10

Hierarchical clustering

0.44

Single model

1.14

Group contribution

0.71

FDA

0.65

Nearest neighbor

0.96

Validity criteria fulfilled:
yes
Conclusions:
The predicted bioconcentration factor of trioctyl benzene-1,2,4-tricarboxylate was 6.03
Executive summary:

The predicted bioconcentration factor of trioctyl benzene-1,2,4-tricarboxylate was 6.03

Endpoint:
bioaccumulation in aquatic species: fish
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Study period:
January 30, 2015
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 limited documentation / justification
Justification for type of information:
See the attached justification.
Guideline:
other: ECHA Guidance on information requirements and chemical safety assessment - Chapter R.06: QSARs and grouping of chemicals
Principles of method if other than guideline:
See the justification for type of information.
Details on estimation of bioconcentration:
BASIS FOR CALCULATION OF BCF
- Estimation software: T.E.S.T. v.4.1 (2012)
Type:
BCF
Value:
6.03 dimensionless

Predicted Bioconcentration factor at 25 deg C for trioctyl benzene-1,2,4-tricarboxylate from Consensus method

 

Prediction results

Endpoint

Experimental value

Predicted value

Bioaccumulation factor Log10

N/A

0.78

Bioaccumulation factor

N/A

6.03

 

Individual Predictions

Method

Predicted value
Log10

Hierarchical clustering

0.44

Single model

1.14

Group contribution

0.71

FDA

0.65

Nearest neighbor

0.96

Validity criteria fulfilled:
yes
Conclusions:
The predicted bioconcentration factor of trioctyl benzene-1,2,4-tricarboxylate was 6.03
Executive summary:

The predicted bioconcentration factor of trioctyl benzene-1,2,4-tricarboxylate was 6.03

Description of key information

Calculated BCF is 251 L/kg wet weight

Key value for chemical safety assessment

BCF (aquatic species):
251 L/kg ww

Additional information

EPA BCFBAF model

The BCF of the substance was estimated to be: 251 L/kg ww

The BAF of the substance was estimated to be: 1.14 L/kg ww.

The Bio Half-Life was estimated to be: 0.226 days (normalized to 10 g fish at 15 deg C).

EPA T.E.S.T. model

The BCF of the substance was estimated to be: 6.03

The highest value of BCF was selected for the chemical safety assessment.

It is therefore concluded that the potential for bioaccumulation of trioctyl benzene-1,2,4-tricarboxylate (DIPLAST TM 8) is very low.