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Bioaccumulation: aquatic / sediment

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Endpoint:
bioaccumulation in aquatic species: fish
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
3 (not reliable)
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
Justification for type of information:
1.1 CAS number: 126050-54-2
1.2 EC number: 418-310-3
1.3 Chemical name:
IUPAC: 2,2'-methylenebis(4,6-di-tert-butyl-phenyl)-2-ethylhexyl phosphite
Other: HP-10
Other: ADK STAB HP-10
1.5 Structure codes
SMILES: CCCCC(CC)COP1Oc2c(Cc3cc(cc(c3O1)C(C)(C)C)C(C)(C)C)cc(cc2C(C)(C)C)C(C)(C)C
InChI: 1/C37H59O3P/c1-15-17-18-25(16-2)24-38-41-39-32-26(20-28(34(3,4)5)22-30(32)36(9,10)11)19-27-21-29(35(6,7)8)23-31(33(27)40-41)37(12,13)14/h20-23,25H,15-19,24H2,1-14H3
Stereochemical features: Not applicable

General Information
2.1 Date of QPRF: 20 June 2019
2.2: Author and contact details: Dr. Stefan Pudenz, Envigo CRS Switzerland Ltd., Rheinstrasse 74, 4414 Füllinsdorf, Switzerland, Email: stefan.pudenz@envigo.com

3 Prediction
3.1 Endpoint (OECD Principle 1)
Endpoint: Bioconcentration factor (BCF) in fish
Dependent variable: BCF log(L/kg)

3.2 Algorithm (OECD Principle 2)
Model or submodel name: BCFBAF
Model version: V3.01
Reference to QMRF: There is no QMRF available. Information to BCFBAF can be found at https://www.epa.gov.
Predicted values (model result): Log BCF = 0.50 (BCF = 3.16 L/kg)
Predicted values (comments) -
Input for prediction: Smiles
Calculated descriptor values: See, software printout

3.3 Applicability domain (OECD Principle 3)
Domains i. Log Kow of the query compound (15.43) is outside the range of the model, while the mol weight is well within the range of the model.
ii. All fragments of the query compound have been found in the compounds of the training set and in the model respectively.
iii. SAR based on fragments

Structural analogues: BCFBAF does not provide information on structural analogues.
Consideration on structural analogues: Not applicable, see above.

3.4 The uncertainty of the prediction (OECD principle 4)
Uncertainty is indicated due to the log Kow outside the range.

3.5 The chemical and biological mechanisms according to the model underpinning the predicted result (OECD principle 5)
SAR based on structural classes

4 Adequacy (Optional)
4.1 Regulatory purpose: Bioconcentration factor endpoint for use in PBT assessment
4.2 Approach for regulatory interpretation of the model result: Unit conversion provided by the software.
4.3 Outcome: Due to uncertainty there is only low confidence in the prediction, which suggests the query compound not to be bioaccumulative.
4.4 Conclusion: The prediction is considered to be of low reliability and will be used together with results from other QSARs in a weight of evidence.

Qualifier:
no guideline followed
Principles of method if other than guideline:
- Principle of test: QSAR prediction of the potential for bioaccumulation
- Short description of test conditions: n/a
- Parameters analysed / observed: Log BCF [L/kg]
Type:
BCF
Value:
3.16 L/kg
Remarks on result:
other:
Remarks:
BCF value based on QSAR prediction.

1.1 CAS number: 126050-54-2

1.2 EC number: 418-310-3

1.3 Chemical name:              

IUPAC: 2,2'-methylenebis(4,6-di-tert-butyl-phenyl)-2-ethylhexyl phosphite

Other: HP-10

Other: ADK STAB HP-10

1.5 Structure codes              

SMILES: CCCCC(CC)COP1Oc2c(Cc3cc(cc(c3O1)C(C)(C)C)C(C)(C)C)cc(cc2C(C)(C)C)C(C)(C)C

InChI: 1/C37H59O3P/c1-15-17-18-25(16-2)24-38-41-39-32-26(20-28(34(3,4)5)22-30(32)36(9,10)11)19-27-21-29(35(6,7)8)23-31(33(27)40-41)37(12,13)14/h20-23,25H,15-19,24H2,1-14H3

Stereochemical features: Not applicable

General Information              

2.1 Date of QPRF: 20 June 2019

2.2: Author and contact details: Dr. Stefan Pudenz, Envigo CRS Switzerland Ltd., Rheinstrasse 74, 4414 Füllinsdorf, Switzerland, Email: stefan.pudenz@envigo.com

3 Prediction              

3.1 Endpoint (OECD Principle 1)       

Endpoint: Bioconcentration factor (BCF) in fish

Dependent variable: BCF log(L/kg)

3.2 Algorithm (OECD Principle 2)       

Model or submodel name: BCFBAF

Model version: V3.01

Reference to QMRF: There is no QMRF available. Information to BCFBAF can be found at https://www.epa.gov.

Predicted values (model result): Log BCF = 0.50 (BCF = 3.16 L/kg)

Predicted values (comments)       -

Input for prediction: Smiles

Calculated descriptor values: See, software printout

3.3 Applicability domain (OECD Principle 3)

Domains       i.       Log Kow of the query compound (15.43) is outside the range of the model, while the mol weight is well within the range of the model.

      ii.       All fragments of the query compound have been found in the compounds of the training set and in the model respectively.

      iii.       SAR based on fragments

Structural analogues: BCFBAF does not provide information on structural analogues.

Consideration on structural analogues: Not applicable, see above.

3.4 The uncertainty of the prediction (OECD principle 4)

Uncertainty is indicated due to the log Kow outside the range.

3.5 The chemical and biological mechanisms according to the model underpinning the predicted result (OECD principle 5)

SAR based on structural classes

4 Adequacy (Optional)              

4.1 Regulatory purpose: Bioconcentration factor endpoint for use in PBT assessment

4.2 Approach for regulatory interpretation of the model result: Unit conversion provided by the software.

4.3 Outcome: Due to uncertainty there is only low confidence in the prediction, which suggests the query compound not to be bioaccumulative.

4.4 Conclusion: The prediction is considered to be of low reliability and will be used together with results from other QSARs in a weight of evidence.

Conclusions:
The prediction is considered to be of low reliability and will be used together with results from other QSARs in a weight of evidence.
Endpoint:
bioaccumulation in aquatic species: fish
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
3 (not reliable)
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
Justification for type of information:
1.1 CAS number: 126050-54-2
1.2 EC number: 418-310-3
1.3 Chemical name:
IUPAC: 2,2'-methylenebis(4,6-di-tert-butyl-phenyl)-2-ethylhexyl phosphite
Other: HP-10
Other: ADK STAB HP-10
1.5 Structure codes
SMILES: CCCCC(CC)COP1Oc2c(Cc3cc(cc(c3O1)C(C)(C)C)C(C)(C)C)cc(cc2C(C)(C)C)C(C)(C)C
InChI: 1/C37H59O3P/c1-15-17-18-25(16-2)24-38-41-39-32-26(20-28(34(3,4)5)22-30(32)36(9,10)11)19-27-21-29(35(6,7)8)23-31(33(27)40-41)37(12,13)14/h20-23,25H,15-19,24H2,1-14H3
Stereochemical features: Not applicable

General Information
2.1 Date of QPRF: 20 June 2019
2.2: Author and contact details: Dr. Stefan Pudenz, Envigo CRS Switzerland Ltd., Rheinstrasse 74, 4414 Füllinsdorf, Switzerland, Email: stefan.pudenz@envigo.com

3 Prediction
3.1 Endpoint (OECD Principle 1)
Endpoint: Bioconcentration factor (BCF) in fish
Dependent variable: BCF log(L/kg)
3.2 Algorithm (OECD Principle 2)
Model or submodel name: BCF Model (CAESAR) within VEGA 1.1.4
Model version: 2.1.14
Reference to QMRF: There is no QMRF available. Information to the VEGA models can be found at vega-qsar.eu

Predicted values (model result):

Predicted BCF [log(L/kg)]: 1.12
Predicted BCF [L/kg]: 13
Predicted BCF from sub-model 1 (HM) [log(L/kg)]: 1.75
Predicted BCF from sub-model 2 (GA) [log(L/kg)]: 0.91
Predicted LogP (MLogP): 7.69

Predicted values (comments):According to VEGA’s evaluation scheme, the result may be not reliable.
Input for prediction: Smiles
Descriptor values: Not provided by the software

3.3 Applicability domain (OECD Principle 3)
Domains i. According to VEGA’s evaluation scheme, the predicted compound is outside the Applicability Domain of the model
ii. One atom centered fragments of the query compound has only been found infrequently in the compounds of the training set. In addition, one descriptor is out of range.
iii. Structural alerts: 2 t-butyl linked to aromatic (SO 02); PO2 residue (SR 03)

Structural analogues

i. CAS 60628-17-3; Phosphorous acid, diphenyl tridecyl ester
ii. CAS 26967-76-0; Tris(isopropylphenyl)phosphates
iii. CAS 29761-21-5; Isodecyl diphenyl phosphate
iv. CAS 119-47-1; p-Cresol, 2,2'-methylenebis(6-tert- butyl-

Consideration on structural analogues: With 78.4% the average similarity of the four most similar analogues in the training set to the query structure is considered moderate to high. Predicted and actual value of the most similar structures vary by a factor of up 11.8 which is above a default factor of 10 often used in traditional risk assessment of environmental chemicals to compensate for uncertainties*. Accuracy is therefore considered low. Study values of the most similar structures disagree with the predicted result for the query structure, thus indicating low concordance. The three most similar compounds also trigger SR02 alert.

3.4 The uncertainty of the prediction (OECD principle 4)
Low accuracy, low concordance, moderate similarity, one descriptor out of range and one fragment only found infrequently in the compounds of the training set suggest uncertainty.

3.5 The chemical and biological mechanisms according to the model underpinning the predicted result (OECD principle 5)
Not applicable since statistical model

4 Adequacy (Optional)
4.1 Regulatory purpose: Bioconcentration factor endpoint for use in PBT assessment
4.2 Approach for regulatory interpretation of the model result: Unit conversion provided by the software.
4.3 Outcome: The predicted value suggest the query compound not to be bioaccumulative, but there is only low confidence in the prediction due to the uncertainties described previously.
4.4 Conclusion: The prediction is considered to be of low reliability and will be used together with results from other QSARs in a weight of evidence.

Qualifier:
no guideline followed
Principles of method if other than guideline:
- Principle of test: QSAR prediction of the potential for bioaccumulation
- Short description of test conditions: n/a
- Parameters analysed / observed: Log BCF [L/kg]
Type:
BCF
Value:
13 L/kg
Remarks on result:
other:
Remarks:
BCF value based on QSAR prediction.
Type:
other: Log BCF
Value:
1.12 L/kg
Remarks on result:
other:
Remarks:
BCF Value based on QSAR prediction.
Type:
other: Log BCF
Value:
1.75 L/kg
Remarks on result:
other:
Remarks:
BCF value based on QSAR prediction.
Type:
other: Log BCF
Value:
0.91 L/kg
Remarks on result:
other:
Remarks:
BCF Value based on QSAR prediction
Type:
other: Log P
Value:
7.69 dimensionless
Remarks on result:
other:
Remarks:
MLogP value based on QSAR prediction.

1.1 CAS number: 126050-54-2

1.2 EC number: 418-310-3

1.3 Chemical name:              

IUPAC: 2,2'-methylenebis(4,6-di-tert-butyl-phenyl)-2-ethylhexyl phosphite

Other: HP-10

Other: ADK STAB HP-10

1.5 Structure codes              

SMILES: CCCCC(CC)COP1Oc2c(Cc3cc(cc(c3O1)C(C)(C)C)C(C)(C)C)cc(cc2C(C)(C)C)C(C)(C)C

InChI: 1/C37H59O3P/c1-15-17-18-25(16-2)24-38-41-39-32-26(20-28(34(3,4)5)22-30(32)36(9,10)11)19-27-21-29(35(6,7)8)23-31(33(27)40-41)37(12,13)14/h20-23,25H,15-19,24H2,1-14H3

Stereochemical features: Not applicable

General Information              

2.1 Date of QPRF: 20 June 2019

2.2: Author and contact details: Dr. Stefan Pudenz, Envigo CRS Switzerland Ltd., Rheinstrasse 74, 4414 Füllinsdorf, Switzerland, Email: stefan.pudenz@envigo.com

3 Prediction              

3.1 Endpoint (OECD Principle 1)       

Endpoint: Bioconcentration factor (BCF) in fish

Dependent variable: BCF log(L/kg)

3.2 Algorithm (OECD Principle 2)       

Model or submodel name: BCF Model (CAESAR) within VEGA 1.1.4

Model version: 2.1.14

Reference to QMRF: There is no QMRF available. Information to the VEGA models can be found at vega-qsar.eu

Predicted values (model result):

Predicted BCF [log(L/kg)]: 1.12

Predicted BCF [L/kg]: 13

Predicted BCF from sub-model 1 (HM) [log(L/kg)]: 1.75

Predicted BCF from sub-model 2 (GA) [log(L/kg)]: 0.91

Predicted LogP (MLogP): 7.69

Predicted values (comments):According to VEGA’s evaluation scheme, the result may be not reliable.

Input for prediction: Smiles

Descriptor values: Not provided by the software

3.3 Applicability domain (OECD Principle 3)

Domains       i.       According to VEGA’s evaluation scheme, the predicted compound is outside the Applicability Domain of the model

      ii.       One atom centered fragments of the query compound has only been found infrequently in the compounds of the training set. In addition, one descriptor is out of range.

      iii.       Structural alerts: 2 t-butyl linked to aromatic (SO 02); PO2 residue (SR 03)

Structural analogues       

i.       CAS 60628-17-3; Phosphorous acid, diphenyl tridecyl ester

ii.       CAS 26967-76-0; Tris(isopropylphenyl)phosphates

iii.       CAS 29761-21-5; Isodecyl diphenyl phosphate

iv.       CAS 119-47-1; p-Cresol, 2,2'-methylenebis(6-tert- butyl-

Consideration on structural analogues: With 78.4% the average similarity of the four most similar analogues in the training set to the query structure is considered moderate to high. Predicted and actual value of the most similar structures vary by a factor of up 11.8 which is above a default factor of 10 often used in traditional risk assessment of environmental chemicals to compensate for uncertainties*. Accuracy is therefore considered low. Study values of the most similar structures disagree with the predicted result for the query structure, thus indicating low concordance. The three most similar compounds also trigger SR02 alert.

3.4 The uncertainty of the prediction (OECD principle 4)

Low accuracy, low concordance, moderate similarity, one descriptor out of range and one fragment only found infrequently in the compounds of the training set suggest uncertainty.

3.5 The chemical and biological mechanisms according to the model underpinning the predicted result (OECD principle 5)

Not applicable since statistical model

4 Adequacy (Optional)              

4.1 Regulatory purpose: Bioconcentration factor endpoint for use in PBT assessment

4.2 Approach for regulatory interpretation of the model result: Unit conversion provided by the software.

4.3 Outcome: The predicted value suggest the query compound not to be bioaccumulative, but there is only low confidence in the prediction due to the uncertainties described previously.

4.4 Conclusion: The prediction is considered to be of low reliability and will be used together with results from other QSARs in a weight of evidence.

Conclusions:
The prediction is considered to be of low reliability and will be used together with results from other QSARs in a weight of evidence.
Endpoint:
bioaccumulation in aquatic species: fish
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
3 (not reliable)
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
Justification for type of information:
1.1 CAS number: 126050-54-2
1.2 EC number: 418-310-3
1.3 Chemical name:
IUPAC: 2,2'-methylenebis(4,6-di-tert-butyl-phenyl)-2-ethylhexyl phosphite
Other: HP-10
Other: ADK STAB HP-10
1.5 Structure codes
SMILES: CCCCC(CC)COP1Oc2c(Cc3cc(cc(c3O1)C(C)(C)C)C(C)(C)C)cc(cc2C(C)(C)C)C(C)(C)C
InChI: 1/C37H59O3P/c1-15-17-18-25(16-2)24-38-41-39-32-26(20-28(34(3,4)5)22-30(32)36(9,10)11)19-27-21-29(35(6,7)8)23-31(33(27)40-41)37(12,13)14/h20-23,25H,15-19,24H2,1-14H3
Stereochemical features: Not applicable

General Information
2.1 Date of QPRF: 20 June 2019
2.2: Author and contact details: Dr. Stefan Pudenz, Envigo CRS Switzerland Ltd., Rheinstrasse 74, 4414 Füllinsdorf, Switzerland, Email: stefan.pudenz@envigo.com

3 Prediction
3.1 Endpoint (OECD Principle 1)
Endpoint: Bioconcentration factor (BCF) in fish
Dependent variable: BCF log(L/kg)

3.2 Algorithm (OECD Principle 2)
Model or submodel name: BCF model (kNN/Read-Across) within VEGA 1.1.4
Model version: 1.1.0
Reference to QMRF: The corresponding QMRF VEGA BCF model (kNN/Read-Across) is available from JRC QSAR Model Database 1(https://qsardb.jrc.ec.europa.eu/qmrf; ID: Q17-24a-0010)
Predicted values (model result): Predicted BCF [log(L/kg)]: 2.04
Predicted values (comments): According to VEGA’s evaluation scheme the result may be not reliable.
Input for prediction: Smiles
Descriptor values: Not provided by the software

3.3 Applicability domain (OECD Principle 3)
Domains
i. According to VEGA’s evaluation scheme, the predicted compound is outside the Applicability Domain of the model
ii. One atom centered fragments of the query compound has only been found infrequently in the compounds of the training set.
iii. Structural alerts are not applicable read-across model

Structural analogues
i. CAS 60628-17-3; Phosphorous acid, diphenyl tridecyl ester CAS 57837-19-1
ii. CAS 26967-76-0; Tris(isopropylphenyl)phosphates CAS 71626-11-4
iii. CAS 29761-21-5; Isodecyl diphenyl phosphate CAS 15972-60-8
iv. CAS 119-47-1; p-Cresol, 2,2'-methylenebis(6-tert- butyl- CAS 34256-82-1

Consideration on structural analogues: With 78.4% the average similarity of the four most similar analogues in the training set to the query structure is considered moderate to high. Predicted and actual value of the most similar structures vary by a factor of up 12.3 which is above a default factor of 10 often used in traditional risk assessment of environmental chemicals to compensate for uncertainties*. Accuracy is therefore considered low. Study values of the most similar structures almost agree with the predicted result for the query structure, thus indicating moderate concordance.

3.4 The uncertainty of the prediction (OECD principle 4)
Moderate concordance and similarity and low accuracy with regard to the similar structures suggests uncertainty and therefore confidence in the prediction is low..

3.5 The chemical and biological mechanisms according to the model underpinning the predicted result (OECD principle 5)
Not applicable since statistical model

4 Adequacy (Optional)
4.1 Regulatory purpose: Bioconcentration factor endpoint for use in PBT assessment
4.2 Approach for regulatory interpretation of the model result: Unit conversion provided by the software.
4.3 Outcome: The predicted value suggest the query compound not to be bioaccumulative, but there is only low confidence in the prediction due to the uncertainties described previously.
4.4 Conclusion: The prediction is considered to be of low reliability and will be used together with results from other QSARs in a weight of evidence.


Qualifier:
no guideline followed
Principles of method if other than guideline:
- Principle of test: QSAR prediction of the potential for bioaccumulation
- Short description of test conditions: n/a
- Parameters analysed / observed: Log BCF [L/kg]
Type:
other: Log BCF
Value:
2.04 L/kg
Remarks on result:
other:
Remarks:
BCF value based on QSAR prediction.

1.1 CAS number: 126050-54-2

1.2 EC number: 418-310-3

1.3 Chemical name:              

IUPAC: 2,2'-methylenebis(4,6-di-tert-butyl-phenyl)-2-ethylhexyl phosphite

Other: HP-10

Other: ADK STAB HP-10

1.5 Structure codes              

SMILES: CCCCC(CC)COP1Oc2c(Cc3cc(cc(c3O1)C(C)(C)C)C(C)(C)C)cc(cc2C(C)(C)C)C(C)(C)C

InChI: 1/C37H59O3P/c1-15-17-18-25(16-2)24-38-41-39-32-26(20-28(34(3,4)5)22-30(32)36(9,10)11)19-27-21-29(35(6,7)8)23-31(33(27)40-41)37(12,13)14/h20-23,25H,15-19,24H2,1-14H3

Stereochemical features: Not applicable

General Information              

2.1 Date of QPRF: 20 June 2019

2.2: Author and contact details: Dr. Stefan Pudenz, Envigo CRS Switzerland Ltd., Rheinstrasse 74, 4414 Füllinsdorf, Switzerland, Email: stefan.pudenz@envigo.com

3 Prediction              

3.1 Endpoint (OECD Principle 1)       

Endpoint: Bioconcentration factor (BCF) in fish

Dependent variable: BCF log(L/kg)

3.2 Algorithm (OECD Principle 2)       

Model or submodel name: BCF model (kNN/Read-Across) within VEGA 1.1.4

Model version: 1.1.0

Reference to QMRF: The corresponding QMRF VEGA BCF model (kNN/Read-Across) is available from JRC QSAR Model Database 1(https://qsardb.jrc.ec.europa.eu/qmrf; ID: Q17-24a-0010)

Predicted values (model result): Predicted BCF [log(L/kg)]: 2.04

Predicted values (comments): According to VEGA’s evaluation scheme the result may be not reliable.

Input for prediction: Smiles

Descriptor values: Not provided by the software

3.3 Applicability domain (OECD Principle 3)

Domains       

i.       According to VEGA’s evaluation scheme, the predicted compound is outside the Applicability Domain of the model

ii.       One atom centered fragments of the query compound has only been found infrequently in the compounds of the training set.

iii.       Structural alerts are not applicable read-across model

Structural analogues       

i.       CAS 60628-17-3; Phosphorous acid, diphenyl tridecyl ester       CAS 57837-19-1

ii.       CAS 26967-76-0; Tris(isopropylphenyl)phosphates       CAS 71626-11-4

iii.       CAS 29761-21-5; Isodecyl diphenyl phosphate       CAS 15972-60-8

iv.       CAS 119-47-1; p-Cresol, 2,2'-methylenebis(6-tert- butyl-       CAS 34256-82-1

Consideration on structural analogues: With 78.4% the average similarity of the four most similar analogues in the training set to the query structure is considered moderate to high. Predicted and actual value of the most similar structures vary by a factor of up 12.3 which is above a default factor of 10 often used in traditional risk assessment of environmental chemicals to compensate for uncertainties*. Accuracy is therefore considered low. Study values of the most similar structures almost agree with the predicted result for the query structure, thus indicating moderate concordance.

3.4 The uncertainty of the prediction (OECD principle 4)

Moderate concordance and similarity and low accuracy with regard to the similar structures suggests uncertainty and therefore confidence in the prediction is low..

3.5 The chemical and biological mechanisms according to the model underpinning the predicted result (OECD principle 5)

Not applicable since statistical model

4 Adequacy (Optional)              

4.1 Regulatory purpose: Bioconcentration factor endpoint for use in PBT assessment

4.2 Approach for regulatory interpretation of the model result: Unit conversion provided by the software.

4.3 Outcome: The predicted value suggest the query compound not to be bioaccumulative, but there is only low confidence in the prediction due to the uncertainties described previously.

4.4 Conclusion: The prediction is considered to be of low reliability and will be used together with results from other QSARs in a weight of evidence.

Conclusions:
The prediction is considered to be of low reliability and will be used together with results from other QSARs in a weight of evidence.
Endpoint:
bioaccumulation in aquatic species: fish
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
3 (not reliable)
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
Justification for type of information:
1.1 CAS number: 126050-54-2
1.2 EC number: 418-310-3
1.3 Chemical name:
IUPAC: 2,2'-methylenebis(4,6-di-tert-butyl-phenyl)-2-ethylhexyl phosphite
Other: HP-10
Other: ADK STAB HP-10
1.5 Structure codes
SMILES: CCCCC(CC)COP1Oc2c(Cc3cc(cc(c3O1)C(C)(C)C)C(C)(C)C)cc(cc2C(C)(C)C)C(C)(C)C
InChI: 1/C37H59O3P/c1-15-17-18-25(16-2)24-38-41-39-32-26(20-28(34(3,4)5)22-30(32)36(9,10)11)19-27-21-29(35(6,7)8)23-31(33(27)40-41)37(12,13)14/h20-23,25H,15-19,24H2,1-14H3
Stereochemical features: Not applicable

General Information
2.1 Date of QPRF: 20 June 2019
2.2: Author and contact details: Dr. Stefan Pudenz, Envigo CRS Switzerland Ltd., Rheinstrasse 74, 4414 Füllinsdorf, Switzerland, Email: stefan.pudenz@envigo.com

3 Prediction
3.1 Endpoint (OECD Principle 1)
Endpoint: Bioconcentration factor (BCF) in fish
Dependent variable: BCF log(L/kg)
3.2 Algorithm (OECD Principle 2)
Model or submodel name: BCF model (Meylan) within VEGA 1.1.4
Model version: 1.0.3
Reference to QMRF: The corresponding QMRF VEGA BCF model (Meylan) is available from JRC QSAR Model Database (https://qsardb.jrc.ec.europa.eu/qmrf; ID: Q17-24a-0010)
Predicted values (model result):
Predicted BCF [log(L/kg)]: 1.09
Predicted BCF [L/kg]: 12
Predicted LogP (Meylan/Kowwin): 13.2
Predicted LogP reliability: Low
Predicted values (comments): According to VEGA’s evaluation scheme, the result may be not reliable.
Input for prediction: Smiles
Descriptor values: Not provided by the software

3.3 Applicability domain (OECD Principle 3)
Domains i. According to VEGA’s evaluation scheme, the predicted compound is out of the Applicability Domain of the model
ii. One atom centered fragments of the query compound has not been found in the compounds of the training set. LogP is out of descriptor range
iii. No structural alerts

Structural analogues
i. CAS 29761-21-5; Isodecyl diphenyl phosphate
ii. CAS 119-47-1; p-Cresol, 2,2'-methylenebis(6-tert- butyl-
iii. CAS 1241-94-7; Octicizer
iv. CAS 78-30-8; Tri-o-cresyl phosphate

Consideration on structural analogues: With 76.1% the average similarity of the four most similar analogues in the training set to the query structure may be considered moderate to high. Predicted and actual value of the most similar structures vary by a factor of up 6.8 which is within a default factor of 10 often used in traditional risk assessment of environmental chemicals to compensate for uncertainties*. Accuracy is therefore considered acceptable. Study values of the similar structures disagree with the predicted result for the query structure, thus indicating low concordance.

3.4 The uncertainty of the prediction (OECD principle 4)
Low concordance, moderate similarity, a descriptor out of range and a fragment not found indicate uncertainty and suggest only low confidence in the prediction.

3.5 The chemical and biological mechanisms according to the model underpinning the predicted result (OECD principle 5)
Not applicable since statistical model

4 Adequacy (Optional)
4.1 Regulatory purpose: Bioconcentration factor endpoint for use in PBT assessment
4.2 Approach for regulatory interpretation of the model result: Unit conversion provided by the software.
4.3 Outcome: The predicted value suggest the query compound not to be bioaccumulative, but there is only low confidence in the prediction due to the uncertainties described previously.
4.4 Conclusion: The prediction is considered to be of low reliability and will be used together with results from other QSARs in a weight of evidence.

Qualifier:
no guideline followed
Principles of method if other than guideline:
- Principle of test: QSAR prediction of the potential for bioaccumulation
- Short description of test conditions: n/a
- Parameters analysed / observed: Log BCF [L/kg]
Type:
other: Log BCF
Value:
1.09 L/kg
Remarks on result:
other:
Remarks:
BCF value based on QSAR prediction.
Type:
BCF
Value:
12 L/kg
Remarks on result:
other:
Remarks:
BCF value based on QSAR prediction.
Type:
other: Log P
Value:
13.2 dimensionless
Remarks on result:
other:
Remarks:
Log P value based on QSAR prediction

1.1 CAS number: 126050-54-2

1.2 EC number: 418-310-3

1.3 Chemical name:              

IUPAC: 2,2'-methylenebis(4,6-di-tert-butyl-phenyl)-2-ethylhexyl phosphite

Other: HP-10

Other: ADK STAB HP-10

1.5 Structure codes              

SMILES: CCCCC(CC)COP1Oc2c(Cc3cc(cc(c3O1)C(C)(C)C)C(C)(C)C)cc(cc2C(C)(C)C)C(C)(C)C

InChI: 1/C37H59O3P/c1-15-17-18-25(16-2)24-38-41-39-32-26(20-28(34(3,4)5)22-30(32)36(9,10)11)19-27-21-29(35(6,7)8)23-31(33(27)40-41)37(12,13)14/h20-23,25H,15-19,24H2,1-14H3

Stereochemical features: Not applicable

General Information              

2.1 Date of QPRF: 20 June 2019

2.2: Author and contact details: Dr. Stefan Pudenz, Envigo CRS Switzerland Ltd., Rheinstrasse 74, 4414 Füllinsdorf, Switzerland, Email: stefan.pudenz@envigo.com

3 Prediction              

3.1 Endpoint (OECD Principle 1)       

Endpoint: Bioconcentration factor (BCF) in fish

Dependent variable: BCF log(L/kg)

3.2 Algorithm (OECD Principle 2)       

Model or submodel name: BCF model (Meylan)  within VEGA 1.1.4

Model version: 1.0.3

Reference to QMRF: The corresponding QMRF VEGA BCF model (Meylan) is available from JRC QSAR Model Database (https://qsardb.jrc.ec.europa.eu/qmrf; ID: Q17-24a-0010)

Predicted values (model result):       

Predicted BCF [log(L/kg)]: 1.09

Predicted BCF [L/kg]: 12

Predicted LogP (Meylan/Kowwin): 13.2

Predicted LogP reliability: Low

Predicted values (comments): According to VEGA’s evaluation scheme, the result may be not reliable.

Input for prediction: Smiles

Descriptor values: Not provided by the software

3.3 Applicability domain (OECD Principle 3)

Domains       i.       According to VEGA’s evaluation scheme, the predicted compound is out of the Applicability Domain of the model

      ii.       One atom centered fragments of the query compound has not been found in the compounds of the training set. LogP is out of descriptor range

      iii.       No structural alerts

Structural analogues       

i.       CAS 29761-21-5; Isodecyl diphenyl phosphate

ii.       CAS 119-47-1; p-Cresol, 2,2'-methylenebis(6-tert- butyl-

iii.       CAS 1241-94-7; Octicizer

iv.       CAS 78-30-8; Tri-o-cresyl phosphate

Consideration on structural analogues: With 76.1% the average similarity of the four most similar analogues in the training set to the query structure may be considered moderate to high. Predicted and actual value of the most similar structures vary by a factor of up 6.8 which is within a default factor of 10 often used in traditional risk assessment of environmental chemicals to compensate for uncertainties*. Accuracy is therefore considered acceptable. Study values of the similar structures disagree with the predicted result for the query structure, thus indicating low concordance.

3.4 The uncertainty of the prediction (OECD principle 4)

Low concordance, moderate similarity, a descriptor out of range and a fragment not found indicate uncertainty and suggest only low confidence in the prediction.

3.5 The chemical and biological mechanisms according to the model underpinning the predicted result (OECD principle 5)

Not applicable since statistical model

4 Adequacy (Optional)              

4.1 Regulatory purpose: Bioconcentration factor endpoint for use in PBT assessment

4.2 Approach for regulatory interpretation of the model result: Unit conversion provided by the software.

4.3 Outcome: The predicted value suggest the query compound not to be bioaccumulative, but there is only low confidence in the prediction due to the uncertainties described previously.

4.4 Conclusion: The prediction is considered to be of low reliability and will be used together with results from other QSARs in a weight of evidence.

Conclusions:
The prediction is considered to be of low reliability and will be used together with results from other QSARs in a weight of evidence.
Endpoint:
bioaccumulation in aquatic species: fish
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
3 (not reliable)
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
Justification for type of information:
1.1 CAS number: 126050-54-2
1.2 EC number: 418-310-3
1.3 Chemical name:
IUPAC: 2,2'-methylenebis(4,6-di-tert-butyl-phenyl)-2-ethylhexyl phosphite
Other: HP-10
Other: ADK STAB HP-10
1.5 Structure codes
SMILES: CCCCC(CC)COP1Oc2c(Cc3cc(cc(c3O1)C(C)(C)C)C(C)(C)C)cc(cc2C(C)(C)C)C(C)(C)C
InChI: 1/C37H59O3P/c1-15-17-18-25(16-2)24-38-41-39-32-26(20-28(34(3,4)5)22-30(32)36(9,10)11)19-27-21-29(35(6,7)8)23-31(33(27)40-41)37(12,13)14/h20-23,25H,15-19,24H2,1-14H3
Stereochemical features: Not applicable

General Information
2.1 Date of QPRF: 20 June 2019
2.2: Author and contact details: Dr. Stefan Pudenz, Envigo CRS Switzerland Ltd., Rheinstrasse 74, 4414 Füllinsdorf, Switzerland, Email: stefan.pudenz@envigo.com

3 Prediction
3.1 Endpoint (OECD Principle 1)
Endpoint: Bioconcentration factor (BCF) in fish
Dependent variable: BCF log(L/kg)

3.2 Algorithm (OECD Principle 2)
Model or submodel name: ToxRead BCF
Model version: 0.11beta
Reference to QMRF: There is no QMRF available. Information to ToxRead can be found at https://www.vegahub.eu
Predicted values (model result): Overall assessment NOT POSSIBLE
Predicted values (comments): -
Input for prediction: Smiles
Calculated descriptor values: Log Kow = 13.198

3.3 Applicability domain (OECD Principle 3)
Domains i. The query compound is out of the domain due to its predicted high log Kow value
ii. The log Kow is out of range.
iii. Two fragments of the query compound have been found in the compounds of the training set and triggered an alert.

Structural analogues

i. CAS 2502-15-0; Tris(p-isopropylphenyl)phosphate CAS 57837-19-1
ii. CAS 29761-21-5; Isodecyl diphenyl phosphate CAS 71626-11-4
iii. CAS 119-47-1; p-Cresol, 2,2'-methylenebis(6-tert- butyl- CAS 15972-60-8
iv. CAS 60628-17-3; Phosphorous acid, diphenyl tridecyl ester CAS 34256-82-1

Consideration on structural analogues: With 78.4%, the average similarity of the four compounds used for read across and which triggered the same alerts is considered moderate to high. The Log BCFs range between 1.46 and 2.63 with an average of 2.06.

3.4 The uncertainty of the prediction (OECD principle 4)
Uncertainty is indicated due to the log Kow out of range and the fact that no assessment was possible.

3.5 The chemical and biological mechanisms according to the model underpinning the predicted result (OECD principle 5)
Read across based on structural similarities and structural alerts.

4 Adequacy (Optional)
4.1 Regulatory purpose: Bioconcentration factor endpoint for use in PBT assessment
4.2 Approach for regulatory interpretation of the model result: Unit conversion provided by the software.
4.3 Outcome: A predicted value was not provided since the log Kow of the query compound was out of range. Using however the average of the four similar compounds suggests a log BCF of 2.06, which can only be used an indicative value.
4.4 Conclusion: ToxRead provided no assessment and the average log BCF of the four most similar compounds may be used as indicative value.


Qualifier:
no guideline followed
Principles of method if other than guideline:
- Principle of test: QSAR prediction of the potential for bioaccumulation
- Short description of test conditions: n/a
- Parameters analysed / observed: Log BCF [L/kg]
Remarks on result:
not determinable

1.1 CAS number: 126050-54-2

1.2 EC number: 418-310-3

1.3 Chemical name:              

IUPAC: 2,2'-methylenebis(4,6-di-tert-butyl-phenyl)-2-ethylhexyl phosphite

Other: HP-10

Other: ADK STAB HP-10

1.5 Structure codes              

SMILES: CCCCC(CC)COP1Oc2c(Cc3cc(cc(c3O1)C(C)(C)C)C(C)(C)C)cc(cc2C(C)(C)C)C(C)(C)C

InChI: 1/C37H59O3P/c1-15-17-18-25(16-2)24-38-41-39-32-26(20-28(34(3,4)5)22-30(32)36(9,10)11)19-27-21-29(35(6,7)8)23-31(33(27)40-41)37(12,13)14/h20-23,25H,15-19,24H2,1-14H3

Stereochemical features: Not applicable

General Information              

2.1 Date of QPRF: 20 June 2019

2.2: Author and contact details: Dr. Stefan Pudenz, Envigo CRS Switzerland Ltd., Rheinstrasse 74, 4414 Füllinsdorf, Switzerland, Email: stefan.pudenz@envigo.com

3 Prediction              

3.1 Endpoint (OECD Principle 1)       

Endpoint: Bioconcentration factor (BCF) in fish

Dependent variable: BCF log(L/kg)

3.2 Algorithm (OECD Principle 2)       

Model or submodel name: ToxRead BCF

Model version: 0.11beta

Reference to QMRF: There is no QMRF available. Information to ToxRead can be found at https://www.vegahub.eu

Predicted values (model result): Overall assessment NOT POSSIBLE

Predicted values (comments): -

Input for prediction: Smiles

Calculated descriptor values: Log Kow = 13.198

3.3 Applicability domain (OECD Principle 3)

Domains       i.       The query compound is out of the domain due to its predicted high log Kow value

      ii.       The log Kow is out of range.

      iii.       Two fragments of the query compound have been found in the compounds of the training set and triggered an alert.

Structural analogues       

i.       CAS 2502-15-0; Tris(p-isopropylphenyl)phosphate       CAS 57837-19-1

ii.       CAS 29761-21-5; Isodecyl diphenyl phosphate       CAS 71626-11-4

iii.       CAS 119-47-1; p-Cresol, 2,2'-methylenebis(6-tert- butyl-       CAS 15972-60-8

iv.       CAS 60628-17-3; Phosphorous acid, diphenyl tridecyl ester       CAS 34256-82-1

Consideration on structural analogues: With 78.4%, the average similarity of the four compounds used for read across and which triggered the same alerts is considered moderate to high. The Log BCFs range between 1.46 and 2.63 with an average of 2.06.

3.4 The uncertainty of the prediction (OECD principle 4)

Uncertainty is indicated due to the log Kow out of range and the fact that no assessment was possible.

3.5 The chemical and biological mechanisms according to the model underpinning the predicted result (OECD principle 5)

Read across based on structural similarities and structural alerts.

4 Adequacy (Optional)              

4.1 Regulatory purpose: Bioconcentration factor endpoint for use in PBT assessment

4.2 Approach for regulatory interpretation of the model result: Unit conversion provided by the software.

4.3 Outcome: A predicted value was not provided since the log Kow of the query compound was out of range. Using however the average of the four similar compounds suggests a log BCF of 2.06, which can only be used an indicative value.

4.4 Conclusion: ToxRead provided no assessment and the average log BCF of the four most similar compounds may be used as indicative value.

Conclusions:
ToxRead provided no assessment and the average log BCF of the four most similar compounds may be used as indicative value.
Endpoint:
bioaccumulation in aquatic species: fish
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
3 (not reliable)
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
Justification for type of information:
1.1 CAS number: 26050-54-2
1.2 EC number: 418-310-3
1.3 Chemical name
IUPAC: 2,2'-methylenebis(4,6-di-tert-butyl-phenyl)-2-ethylhexyl phosphite
Other: HP-10
Other: ADK STAB HP-10
1.5 Structure codes
SMILES: CCCCC(CC)COP1Oc2c(Cc3cc(cc(c3O1)C(C)(C)C)C(C)(C)C)cc(cc2C(C)(C)C)C(C)(C)C
InChI: 1/C37H59O3P/c1-15-17-18-25(16-2)24-38-41-39-32-26(20-28(34(3,4)5)22-30(32)36(9,10)11)19-27-21-29(35(6,7)8)23-31(33(27)40-41)37(12,13)14/h20-23,25H,15-19,24H2,1-14H3
Stereochemical features: Not applicable

General Information
Date of QPRF: 20 June 2019
Author and contact details: Dr. Stefan Pudenz, Envigo CRS Switzerland Ltd., Rheinstrasse 74, 4414 Füllinsdorf, Switzerland, Email: stefan.pudenz@envigo.com

Prediction
3.1Endpoint (OECD Principle 1)
Endpoint: Bioconcentration factor
Dependent variable: Bioconcentration factor (BCF) log10 L/kg
3.2 Algorithm (OECD Principle 2)
Model or submodel name: US EPA T.E.S.T Bioconcentration factor, Consensus method
Model version: 4.2
Reference to QMRF: There is no QMRF available and provided by US EPA, respectively.
Predicted values (model result): 3.35 log L/kg (2256.62 L/kg)
Predicted values (comments): BCF of the five methods ranges from 1.98 to 6.17 log L/kg.
Input for prediction: Smiles
Descriptor values: Due to the large number of descriptors used all information are attached in the software printout section.

3.3 Applicability domain (OECD Principle 3)
Domains i. Query structure is out of the domain of the consensus model since the variability between the predictions is considered high.
ii. All descriptors of the query structure are within ranges
iii. Considerations on the mechanism domain are not applicable since statistical model

Structural analogues
(training set)
i. CAS 119-47-1, p-Cresol, 2,2'-methylenebis(6-tert- butyl-
ii. CAS 60628-17-3, Phosphorous acid, diphenyl tridecyl ester
iii. CAS 2668-47-5, 2,6-Di-tert-butyl-4-phenylphenol
iv. CAS 346-10-1, N-[4-({2-[2,4-Bis(2-methyl-2-butanyl)phenoxy]butanoyl}amino)-2-hydroxyphenyl]-2,2,3,3,4,4,4-heptafluorobutanamide

Consideration on structural analogues: With 70%, the average similarity between the four most similar structures in the training set and the query structure may be considered moderate. Predicted and experimental values of similar structures vary by a factor of up to 8.7 which is just below a default factor of 10 often used in traditional risk assessment of environmental chemicals to compensate for uncertainties*. Hence concordance between predicted and actual value (accuracy) is considered moderate.

3.4 The uncertainty of the prediction (OECD principle 4)
Moderate similarity and accuracy indicate uncertainty. This is substantiated by a mean absolute error of the predictions with the external test set and the training set being greater than the mean absolute error of the entire set.

3.5 The chemical and biological mechanisms according to the model underpinning the predicted result (OECD principle 5)
Not applicable since statistical model

4 Adequacy (Optional)
4.1 Regulatory purpose: Bioconcentration factor endpoint for use in PBT assessment
4.2 Approach for regulatory interpretation of the model result: Unit conversion provided by the software.
4.3 Outcome: The range of predicted values within the consensus methods is large and thus indicating low confidence in the prediction which is substantiated by only moderate similarity between the query compound and the four most similar compounds in the training set.

4.4 Conclusion
The predicted log BCF of 3.35 L/kg (2256.62 L/kg) is just above the threshold of a substance being considered as bioaccumulative, i.e. 2000 L/kg. Since the prediction is considered to be of low reliability the result may be used together with results from other QSARs in a weight of evidence.
Qualifier:
no guideline followed
Principles of method if other than guideline:
- Principle of test: QSAR prediction of the potential for bioaccumulation
- Short description of test conditions: n/a
- Parameters analysed / observed: Log BCF [L/kg]
Type:
BCF
Value:
2 256.62 L/kg
Remarks on result:
other:
Remarks:
BCF value based on QSAR prediction.

1.1 CAS number: 26050-54-2

1.2 EC number: 418-310-3

1.3 Chemical name              

IUPAC: 2,2'-methylenebis(4,6-di-tert-butyl-phenyl)-2-ethylhexyl phosphite

Other: HP-10

Other: ADK STAB HP-10

1.5 Structure codes              

SMILES: CCCCC(CC)COP1Oc2c(Cc3cc(cc(c3O1)C(C)(C)C)C(C)(C)C)cc(cc2C(C)(C)C)C(C)(C)C

InChI: 1/C37H59O3P/c1-15-17-18-25(16-2)24-38-41-39-32-26(20-28(34(3,4)5)22-30(32)36(9,10)11)19-27-21-29(35(6,7)8)23-31(33(27)40-41)37(12,13)14/h20-23,25H,15-19,24H2,1-14H3

Stereochemical features: Not applicable

General Information              

Date of QPRF: 20 June 2019

Author and contact details: Dr. Stefan Pudenz, Envigo CRS Switzerland Ltd., Rheinstrasse 74, 4414 Füllinsdorf, Switzerland, Email: stefan.pudenz@envigo.com

Prediction              

3.1Endpoint (OECD Principle 1)       

Endpoint: Bioconcentration factor

Dependent variable: Bioconcentration factor (BCF) log10 L/kg

3.2 Algorithm (OECD Principle 2)       

Model or submodel name: US EPA T.E.S.T Bioconcentration factor, Consensus method

Model version: 4.2

Reference to QMRF: There is no QMRF available and provided by US EPA, respectively.

Predicted values (model result): 3.35 log L/kg (2256.62 L/kg)

Predicted values (comments): BCF of the five methods ranges from 1.98 to 6.17 log L/kg.

Input for prediction: Smiles

Descriptor values: Due to the large number of descriptors used all information are attached in the software printout section.

3.3 Applicability domain (OECD Principle 3)

Domains       i.       Query structure is out of the domain of the consensus model since the variability between the predictions is considered high.

      ii.       All descriptors of the query structure are within ranges

      iii.       Considerations on the mechanism domain are not applicable since statistical model

Structural analogues

(training set)       

i.       CAS 119-47-1, p-Cresol, 2,2'-methylenebis(6-tert- butyl-

ii.       CAS 60628-17-3, Phosphorous acid, diphenyl tridecyl ester

iii.       CAS 2668-47-5, 2,6-Di-tert-butyl-4-phenylphenol

iv.       CAS 346-10-1, N-[4-({2-[2,4-Bis(2-methyl-2-butanyl)phenoxy]butanoyl}amino)-2-hydroxyphenyl]-2,2,3,3,4,4,4-heptafluorobutanamide

Consideration on structural analogues: With 70%, the average similarity between the four most similar structures in the training set and the query structure may be considered moderate. Predicted and experimental values of similar structures vary by a factor of up to 8.7 which is just below a default factor of 10 often used in traditional risk assessment of environmental chemicals to compensate for uncertainties*. Hence concordance between predicted and actual value (accuracy) is considered moderate.

3.4 The uncertainty of the prediction (OECD principle 4)

Moderate similarity and accuracy indicate uncertainty. This is substantiated by a mean absolute error of the predictions with the external test set and the training set being greater than the mean absolute error of the entire set.

3.5 The chemical and biological mechanisms according to the model underpinning the predicted result (OECD principle 5)

Not applicable since statistical model

4 Adequacy (Optional)              

4.1 Regulatory purpose: Bioconcentration factor endpoint for use in PBT assessment

4.2 Approach for regulatory interpretation of the model result: Unit conversion provided by the software.

4.3 Outcome: The range of predicted values within the consensus methods is large and thus indicating low confidence in the prediction which is substantiated by only moderate similarity between the query compound and the four most similar compounds in the training set.

4.4 Conclusion

The predicted log BCF of 3.35 L/kg (2256.62 L/kg) is just above the threshold of a substance being considered as bioaccumulative, i.e. 2000 L/kg. Since the prediction is considered to be of low reliability the result may be used together with results from other QSARs in a weight of evidence.

Conclusions:
The predicted log BCF of 3.35 L/kg (2256.62 L/kg) is just above the threshold of a substance being considered as bioaccumulative, i.e. 2000 L/kg. Since the prediction is considered to be of low reliability the result may be used together with results from other QSARs in a weight of evidence.
Endpoint:
bioaccumulation in aquatic species: fish
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
May 26, 1989 - August 7, 1989
Reliability:
3 (not reliable)
Qualifier:
according to
Guideline:
other: Please see version section below.
Version / remarks:
"Method for Testing the Degree of Accumulation of Chemical Substances in Fish Body" stipulated in the "Testing Methods for New Chemical Substances" (July 13, 1974, Kanpogyo No.5, Planning and Coordination Bureau, Environment Agency, Yakuhatu No.615, Pharmaceutical Affairs Bureau, Ministry of Health and Welfare, and 49 Kikyoku No.392, Basic Industries Bureau, Ministry of International Trade and Industry, Japan).
Deviations:
no
GLP compliance:
yes (incl. certificate)
Specific details on test material used for the study:
(1) Supplier: Adeka Argus Chemical Co., Ltd.
(2) Lot number: 102

Physicochemical properties
Appearance: White powder
Melting point: 144ºC
Solubility: Water ≤10 mg/L
Hexane 44 g/L
Chloroform ≥100 g/L
Ethyl acetate 23 g/L
Methanol 160 mg/L

Storage condition: Cold and dark storage place
Stability: The test substance was stable during the exposure period, as shown by the finding that IR spectra of the test substance before the initiation and after the termination of the exposure, were identical under the storage conditions.
Stability under testing conditions: Prior to the bioconcentration test, a stability of the test substance under the testing conditions was confirmed by the preliminary test.
Vehicle:
yes
Details on preparation of test solutions, spiked fish food or sediment:
For the acute toxicyt to Fish test the solutions were prepared as follows:
Preparation of stock solution
(1) Dispersant
HCO-20 (Hydrogenated castor oil)

(2) Preparation
Test substance and HCO-20 (50 times amount of the test substance) were dissolved in tetrahydrofuran. Then the solution was filled up with ion-exchanged water after evaporating tetrahydrofuran to prepare 1000 mg/L stock solution.

For the Bioconcentration test the solutions were prepared as follows:
Preparation of stock solution
(1) Dispersant
HCO-20 (Hydrogenated castor oil)
(2) Preparation
Level 1
200 mg/L stock solution was prepared in the same way as the acute toxicity to Fish test..
Level 2
20 mg/L stock solution was prepared in the same way as the acute toxicity to Fish test..
Control
HCO-20 was dissolved in ion-exchanged water to prepare 10 g/L stock solution.
Each stock solution in 25-L glass bottles was supplied to the test tank.

Test organisms (species):
Cyprinus carpio
Details on test organisms:
Acute toxicity to Fish test:
Test fish
(1) Species Orange-red killifish (Oryzias latipes)
(2) Supplier: Nakashima fish farm (Address : Daimyojin Nagasucho Tamana-gun, Kumamoto 869-01, Japan)
(3) Conditions for fish care
Period etc.
The fish were visually examined upon receiving and those demonstrating any abnormalities were removed. The fish were reared for 49 days following an external disinfection.

External disinfection
The external disinfection for sick prevention was carried out in an aqueous solution containing 20 mg/L ELBAZIU (Ueno Pharm. Co.) and 7 g/L sodium chloride for 24 hours under static condition.

(4) Conditions for acclimatization
The fish were transferred to an acclimatizing aquarium. The fish those demonstrating any abnormality were removed and reared for 21 days in a flow through system at the temperature of 25±2ºC.

(5) Weight average 0.31 g

(6) Length average 3.3 cm

(7) Certification
Fish of Lot No. TFO-890518 which passed the HgCl2-test*2 were prepared for the test.

Bioconcentration test:
Test fish
(1) Species Carp (Cyprinus carpio)
(2) Supplier: Sugishima fish farm (Address : 123-2 Gunchiku Ichibancho, Yatsushiro-shi, Kumamoto 866, Japan)
(3) Conditions for fish care
Period etc.
The fish were visually examined upon receiving and those demonstrating any abnormalities were removed. The fish were reared for 2 days following an external disinfection.

External disinfection
The external disinfection for sick prevention was carried out in an aqueous solution containing 50 mg/L terramycin for fish (Taito Pfizer K.K.) and 7 g/L sodium chloride for 24 hours under static condition.

4) Conditions for acclimatization
The fish were transferred to an acclimatizing aquarium. The fish those demonstrating any abnormalities during this period were removed and reared for 34 days in a flow through system at the temperature of 25±2ºC. The fish were then transferred to test tanks and reared at the same temperature in the flow through system for 33 days.

(5) Weight, length and lipid content at initial exposure
Weight average 23.6 g
Length average 9.9 cm
Lipid content average 3.5%

(6) Feeding
Feed Pelleted feed for carp
Manufacturer Nippon Formula Feed Mfg. Co., Ltd.
Feeding amount and interval
Amount corresponding to about 2% of total body weight was fed twice a day in halves. On the day before fish sampling, no feed was given.

Route of exposure:
aqueous
Test type:
semi-static
Water / sediment media type:
natural water: marine
Test temperature:
25±2ºC
Details on test conditions:
Feeding
Feed: Pelleted feed for carp
Manufacturer: Nippon Formula Feed Mfg. Co., Ltd.
Feeding amount and interval: Amount corresponding to about 2% of total body weight was fed twice a day in halves. On the day before fish sampling, no feed was given.

Dilution water for test:
Origin: Underground water from the premises of Kurume Research Laboratories.
Water quality assessment: Water temperature, pH and dissolved oxygen were continuously measured in our laboratory.
Furthermore, total hardness, evaporated residue, chemical oxygen demand, chloride ion, ammonia nitrogen, harmful substances such as organic phosphorus compounds, cyanide ion and heavy metal etc., were analyzed regularly once a six months.
The quality of dilution water used for the test was confirmed to meet the ministerial ordinance of the Ministry of Public Welfare (August 31, 1978) in total hardness and evaporated residue. The other analyzed items was confirmed to meet the water quality criteria for fisheries (Japan Fisheries Resource Conservation Association, March 1983)

Conditions of test and circumstances
Supply of test water: Flow through system assembled at this laboratory was used.
Test tank: 100-L glass tank.
Flow rate of test water : 2 mL/min for stock solution and 800 mL/min for dilution water; 1155 Liters/day for test water were supplied.
Temperature of test water: 25±2ºC
Concentrations of dissolved oxygen in test tank:
Level 1 6.0 – 6.9 mg/L
Level 2 6.2 – 7.2 mg/L
Control 6.6 – 7.2 mg/L

Number of fish (at initial exposure)
Levels 1 and 2: 15
Control: 5

Duration of exposure: 8 weeks

Nominal and measured concentrations:
Based on preliminary test results for 48-hour LC50 and analytical detection limits, test concentrations of the test substance were decided as follows. Control was also set as a blank test.

Level 1 0.5 mg/L
Level 2 0.05 mg/L
Details on estimation of bioconcentration:

Method of calculation for bioconcentration factor

Bioconcentration factor (BCF) (J) = P × A(f) × B × D A(std) × C - (K × G) × 100 E × G × I

Quantity of test substance in test fish (μg) (F) = P × A(f) × B × D A(std) × C - (K × G) × 100 E

Concentration of test substance in test fish (μg/g) (H) = P × A(f) × B × D A(std) × C - (K × G) × 100 E × G

P : Concentration of test substance in standard solution (µg/mL)
A (std) : Peak height of standard solution (mm)
A (f) : Peak height of test sample solution (mm)
B : Dilution rate
C : Ratio of the portion, used for analysis to whole volume
D : Final volume of sample solution (mL)
E : Recovery rate (%)
G : Weight of test fish (g)
I : Average concentration of test substance in test water (mg/L)
K : Average concentration of blank in test fish of Control before and end of exposure

BCFs were calculated using the equations above and they were rounded off to 2 figures following JIS Z 8401-1961.
Key result
Conc. / dose:
0.5 mg/L
Temp.:
25 °C
Type:
BCF
Value:
0.9 dimensionless
Calculation basis:
steady state
Remarks on result:
other:
Remarks:
≤0.9 – 8.7
Key result
Conc. / dose:
0.05 mg/L
Temp.:
25 °C
Type:
BCF
Value:
<= 9.5 dimensionless
Calculation basis:
steady state
Details on results:
BCFs in Table-2: BCFs were ≤0.9–8.7 (Level 1) and ≤9.5 (Level 2).
No abnormality in behavior or appearance of test fish was noted.
The average concentrations of the test substance in test water are shown in Table-1.
Concentrations of the test substance were maintained ≥85% of nominal concentrations.

Table-1 Measured concentrations of test substance in test water (average value at times from start of exposure)

 

2 weeks

4 weeks

6 weeks

8 weeks

Table

Fig.

Level 1

0.437

0.454

0.457

0.456

4

6

Level 2

0.0462

0.0460

0.0458

0.0451

5

Table 2- BCFs

 

2 weeks

4 weeks

6 weeks

8 weeks

Table

Fig.

Level 1

8.7

≤0.9

≤0.9

3.8

2.2

≤0.9

≤0.9

≤0.9

8

9

Level 2

≤9.5

≤9.5

≤9.5

≤9.5

≤9.5

≤9.5

≤9.5

≤9.5

9

10

Validity criteria fulfilled:
not specified
Conclusions:
Bioconcentration factors
Level 1 ≤0.9 – 8.7
Level 2 ≤9.5
Executive summary:

Title: Bioconcentration test of HP-10 in carp

 2. Test conditions

 2.1 Acute toxicity test

             (1) Test fish                             Orange-red killifish (Oryzias latipes)

             (2) Duration of exposure         48 hrs.

             (3) Exposure method               Semi static system

                                                               (Renewal of test water, at every 8 – 16 hrs.)

 

2.2 Bioconcentration test

             (1) Test fish                             Carp (Cyprinus carpio)

             (2) Nominal concentrations of test substance

                                                               High exposure level (Level 1)     0.5        mg/L

                                                               Low exposure level (Level 2)      0.05      mg/L

             (3) Duration of exposure         8 weeks

             (4) Exposure method               Continuous flow system

             (5) Analytical method             High performance liquid chromatography

 

 

3. Results

 (1) 48-hour LC50value            >50.0 mg/L

 (2) Bioconcentration factors   Level 1             ≤0.9 – 8.7

                                              Level 2             ≤9.5

 4. Stability of test substance

 The test substance was stable under storage and test conditions.

Description of key information

Introduction

The prediction of the potential for bioaccumulation of HP-10 was performed with VEGA NIC 1.1.4 (CAESAR, Meylan, KNN), ToxRead 0.11beta, BCFBAF 3.01 (EpiSuite) and US EPA T.E.S.T. 4.2.

The prediction results are detailed in the (Q)SAR prediction reporting formats (QPRFs) accomplished by the original software printouts. Reliability is assigned to each prediction based on considerations of similar structures in the training set, prediction statistics and the applicability domain. For details, it is referred to the QPRFs.

Appraisal of (Q)SAR Modelling

The predicted log BCF’s of the five methods implemented in US EPA TEST range between 1.98 and 6.17 L/kg and provide a consensus value of 3.35 L/kg. There is however only low confidence in the prediction as the mean absolute error (MAE) for the prediction of structurally similar compounds from both, the external test set and the training set, is greater than the MAE of the entire set. In addition, the structural similarity of the most similar compounds in the training and external test set is considered only low to moderate.

The VEGA models CAESAR, Meylan and KNN/Read Across predicted log BCFs between 1.09 and 2.04 L/kg with however only low confidence in the predictions. ToxRead did not provide an assessment as the log Kowwas out of the range of values of the four most similar analogues. The average BCF of the four analogues is 2.06 and may suggest a low potential for bioaccumulation. The lowest predicted log BCF of 0.5 was provided from the BCFBAF model of the EpiSuite, which is however a default minimum value applied when Log Kow> 7.

Table1   Prediction results for BCF. Predicted Log Kowpresented when used as descriptor in the BCF model.

Model

Log BCF [L/kg]

Log Kow

Reliability

US EPA TEST

3.35

-

Low

CAESAR (VEGA)

1.12

7.69

Low

Meylan (VEGA)

1.09

13.2

Low

KNN/Read-Across (VEGA)

2.04

-

Low

BCFBAF (EPI Suite)

0.5

15.43

Low

ToxRead

2.06

13.2

Low

Conclusion

There is uncertainty in all predictions and therefore confidence in the results is also low. However, with five out of six models predicting BCFs less than 2000 L/kg there is an argument for a weight of evidence that HP-10 is likely to be not bioaccumulative.

Key value for chemical safety assessment

BCF (aquatic species):
3.35 L/kg ww

Additional information

There is uncertainty in all predictions and therefore confidence in the results is also low. However, with five out of six models predicting BCFs less than 2000 L/kg there is an argument for a weight of evidence that HP-10 is likely to be not bioaccumulative. The value used for the Chemical safety assessment is based on the  US EPA TEST model. As there were a range of Log BCF values the value used for the CSR is the highest value out of all six results and therefore is appropriate for the CSR.

A bioaccumulation study was conducted on HP-10 however the study is scored as reliabilty 3. Therefore this study cannot be used to confirm the Bioaccumulation however the study can be used as supporting data in addition to the QSAR results.

All results indicate that HP-10 is not bioaccumulating.