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Bioaccumulation: aquatic / sediment

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Endpoint:
bioaccumulation in aquatic species: fish
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint:
bioaccumulation in aquatic species: fish
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Study period:
2019
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:
Please refer to the QMRF and QPRF files provided under the section attached justification.
Qualifier:
according to
Guideline:
other: REACH Guidance on QSAR R.6
Principles of method if other than guideline:
Estimation of BCF using T.E.S.T. v4.2.1
GLP compliance:
no
Specific details on test material used for the study:
SMILES: CC(C)(c1ccccc1)C(C)(C)c2ccccc2
Test organisms (species):
other: fish
Details on estimation of bioconcentration:
BASIS FOR CALCULATION OF BCF
- Estimation software: US EPA T.E.S.T. v4.2.1

Applied estimation methods:
- Hierarchical method : The toxicity for a given query compound is estimated using the weighted average of the predictions from several different cluster models.
- 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).
- 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).
- Nearest neighbor method : The predicted toxicity is estimated by taking an average of the 3 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 QSAR methods (provided the predictions are within the respective applicability domains; recommended method by T.E.S.T. for providing the most accurate predictions).
Key result
Type:
BCF
Value:
1 275.22 L/kg
Remarks on result:
other: method: consensus
Type:
other: logBCF
Value:
3.11 dimensionless
Remarks on result:
other: method: consensus

Table 1. QSAR Model results

Method

Predicted value

Model statistics

MAE (in log10)

External test set

Training set

log BCF

BCF

No. of chemicals

Entire set

SC >= 0.5

Entire set

SC >= 0.5

Consensus method

3.11

1275.22

-

-

-

0.51

0.43

0.42

0.52

Hierarchical clustering

3.05

1120.10 (88.95-14104.75)

0.748 – 0.853

0.715 – 0.817

223 - 540 (cluster models: 3)

0.54

0.56

0.23

0.25

Single model

3.13

1343.62 (100.31-17998.00)

0.764

0.733

540

0.54

0.34

0.53

0.57

Group contribution

3.74

5439.83 (226.11-130874.08)

0.719

0.527

499

0.62

0.59

0.60

0.64

FDA

2.81

642.20 (100.83-4090.12)

0.682

0.608

40

0.57

0.52

0.53

0.71

Nearest neighbor

2.81

641.41

-

-

3

0.60

0.76

0.55

0.55

 

The substance is within the applicability domain of the Hierarchical clustering method. Based on the mean absolute error for the external test set, the confidence in the predicted BCF values is low.

The substance is within the applicability domain of the FDA method. Based on the mean absolute error for the external test set, the confidence in the predicted BCF values is high.

The substance is within the applicability domain of the Single model method. Based on the mean absolute error for the external test set, the confidence in the predicted BCF values is high.

The substance is within the applicability domain of the Group contribution method. Based on the mean absolute error for the external test set, the confidence in the predicted BCF values is high.

The substance is within the applicability domain of the Nearest neighbor method. Based on the mean absolute error for the external test set, the confidence in the predicted BCF values is low.

The substance is within the applicability domain of the Consensus method. Based on the mean absolute error for the external test set, the confidence in the predicted BCF values is high.

Validity criteria fulfilled:
yes
Conclusions:
Using T.E.S.T. v4.2.1 the BCF value of the test item was calculated to be 1275. The substance is within the applicability domain of the model. Thus, the estimation is considered to be accurate.
Executive summary:

The BCF value was calculated using T.E.S.T v4.2.1 from US Environmental Protection Agency. The BCF value of the test item was calculated to be 1275 L/kg.

The adequacy of a prediction depends on the following conditions:

a) the (Q)SAR model is scientifically valid: the scientific validity is established according to the OECD principles for (Q)SAR validation;

b) the (Q)SAR model is applicable to the query chemical: a (Q)SAR is applicable if the query chemical falls within the defined applicability domain of the model;

c) the (Q)SAR result is reliable: a valid (Q)SAR that is applied to a chemical falling within its applicability domain provides a reliable result;

d) the (Q)SAR model is relevant for the regulatory purpose.

 

For assessment and justification of these 4 requirements the QMRF and QPRF files were developed and attached to this study record.

 

Description of the prediction Model

The prediction model was descripted using the harmonised template for summarising and reporting key information on (Q)SAR models. For more details please refer to the attached QSAR Model Reporting Format (QMRF) file. 

 

Assessment of estimation domain

The assessment of the estimation domain was documented in the QSAR Prediction Reporting Format file (QPRF). Please refer to the attached document for the details of the prediction and the assessment of the estimation domain.

Endpoint:
bioaccumulation: aquatic / sediment
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Study period:
2019
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:
Please refer to the QMRF and QPRF files provided under the section attached justification.
Qualifier:
according to
Guideline:
other: REACH Guidance on QSAR R.6
Principles of method if other than guideline:
Estimation of BCF using VEGA v1.1.4 BCF model CAESAR v2.1.14
GLP compliance:
no
Specific details on test material used for the study:
SMILES: CC(C)(c1ccccc1)C(C)(C)c2ccccc2
Test organisms (species):
other: fish
Details on estimation of bioconcentration:
BASIS INFORMATION
- Measured/calculated logPow: calculated

BASIS FOR CALCULATION OF BCF
- Estimation software: VEGA CAESAR v2.1.14
- Result based on calculated log Pow of: 5.4 (calculated by VEGA)
Key result
Type:
BCF
Value:
999 L/kg
Remarks on result:
other: QSAR predicted value. The substance is within the applicability domain of the model. According to the model’s global AD index, the predicted substanceis into the Applicability Domain of the model.
Type:
other: logBCF
Value:
3 dimensionless
Remarks on result:
other: QSAR prediction value.

According to the model’s global AD index, the predicted substance  is in the Applicability Domain of the model.

Compound: Molecule 0

Compound SMILES: c1ccc(cc1)C(C)(C)C(c2ccccc2)(C)C

Experimental value [log(L/kg)]: -

Predicted BCF [log(L/kg)]: 3

Predicted BCF [L/kg]: 999

Predicted BCF from sub-model 1 (HM) [log(L/kg)]: 3.01

Predicted BCF from sub-model 2 (GA) [log(L/kg)]: 2.81

Predicted LogP (MLogP): 5.4

Structural alerts: -

Reliability: the predicted compound is into the Applicability Domain of the model

Remarks:

none

Validity criteria fulfilled:
yes
Conclusions:
Using CAESAR v2.1.14 the BCF value of the test item was calculated to be 999 L/kg. The substance is within the applicability domain of the model. Thus, the estimation is considered to be accurate.
Executive summary:

The BCF value was calculated using CAESAR v2.1.14 as part of VEGA v1.1.4 from IRCCS - Istituto di Ricerche Farmacologiche Mario Negri.

The BCF value of the test item was calculated to be 999 L/kg (VEGA, 2017).

The adequacy of a prediction depends on the following conditions:

a) the (Q)SAR model is scientifically valid: the scientific validity is established according to the OECD principles for (Q)SAR validation;

b) the (Q)SAR model is applicable to the query chemical: a (Q)SAR is applicable if the query chemical falls within the defined applicability domain of the model;

c) the (Q)SAR result is reliable: a valid (Q)SAR that is applied to a chemical falling within its applicability domain provides a reliable result;

d) the (Q)SAR model is relevant for the regulatory purpose.

 

For assessment and jsutification of these 4 requirements the QMRF and QPRF files were developed and attached to this study record.

 

Description of the prediction Model

The prediction model was descripted using the harmonised template for summarising and reporting key information on (Q)SAR models. For more details please refer to the attached QSAR Model Reporting Format (QMRF) file. 

 

Assessment of estimation domain

The assessment of the estimation domain was documented in the QSAR Prediction Reporting Format file (QPRF). Please refer to the attached document for the details of the prediction and the assessment of the estimation domain.

Description of key information

The performance of a test for bioaccumulation in aquatic species, preferably fish, is scientifically unjustified. Therefore, the bioaccumulation potential of the test item was estimated using QSAR models.

Using VEGA v1.1.4 model CAESAR v2.1.14 the BCF value of the test item was calculated to be 999 L/kg. Using T.E.S.T. v4.2.1 the BCF value of the test item was calculated to be 1275 L/kg. The substance is within the applicability domain of both model. Thus, the estimations are considered to be accurate. For risk assessment purposes as worst case scenario the value of 1275 L/kg was chosen as a key value.

Key value for chemical safety assessment

BCF (aquatic species):
1 275 L/kg ww

Additional information

The performance of a test for bioaccumulation in aquatic species, preferably fish, is scientifically unjustified. REACH Regulation No. 1907/2006, Annex IX, Sect. 9.3.2, Col. 2, states as follows:

“9.3.2 The study need not be conducted if:

- the substance has a low potential for bioaccumulation (for instance a log Kow <= 3) and/or a low potential to cross biological membranes, or

- direct and indirect exposure of the aquatic environment is unlikely. ”

Direct and indirect exposure of the test item to water is highly unlikely. Further, the test item is practically insoluble in water. Therefore, 1,1'-(1,1,2,2-tetramethylethylene)dibenzene was considered to have no bioaccumulation potential. However, due to its low water solubility a test was omitted and a calculation of the BCF was performed and the obtained value was used for risk and PBT assessment.

The adequacy of a prediction depends on the following conditions:

a) the (Q)SAR model is scientifically valid: the scientific validity is established according to the OECD principles for (Q)SAR validation;

b) the (Q)SAR model is applicable to the query chemical: a (Q)SAR is applicable if the query chemical falls within the defined applicability domain of the model;

c) the (Q)SAR result is reliable: a valid (Q)SAR that is applied to a chemical falling within its applicability domain provides a reliable result;

d) the (Q)SAR model is relevant for the regulatory purpose.

 

For assessment and justification of these 4 requirements the QMRF and QPRF files were developed and attached to this study record.

 

Description of the prediction Model

The prediction model was descripted using the harmonised template for summarising and reporting key information on (Q)SAR models. For more details please refer to the attached QSAR Model Reporting Format (QMRF) file. 

 

Assessment of estimation domain

The assessment of the estimation domain was documented in the QSAR Prediction Reporting Format file (QPRF). Please refer to the attached document for the details of the prediction and the assessment of the estimation domain.