Formaldehyde, oligomeric reaction products with acetone and diphenylamine

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

Study period:

28 April 2017

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Validated QSAR calculation method. A validated QPRF is attached. The substance is recognised as part of the rulebase utilised by the EPI Suite model data set, and is in model Applicability Domain. Further details can be found within the appended report below or at http://www.epa.gov/oppt/exposure/pubs/episuite.htm. This system is recognised in ECHA Guidance document CHAPTER R.6 – QSARS AND GROUPING OF CHEMICALS, ref R.6.1.4.3 Use of (Q)SARs for PBT (vPvB) assessment

Justification for type of information:

1. SOFTWARE: US EPA On-Line EPI Suite™ v. 4.11

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

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL:
Three most abundant structures in UVCB substance:
Diphenylamine: InChI=1S/C12H11N/c1-3-7-11(8-4-1)13-12-9-5-2-6-10-12/h1-10,13H
9,10-dihydro-9,9-dimethylacridine: InChI=1S/C15H15N/c1-15(2)11-7-3-5-9-13(11)16-14-10-6-4-8-12(14)15/h3-10,16H,1-2H3
N-phenyl-4-(propan-2-yl)aniline: InChI=1S/C15H17N/c1-12(2)13-8-10-15(11-9-13)16-14-6-4-3-5-7-14/h3-12,16H,1-2H3

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
No QMRF is available.. The model is recognized, and referenced within ECHA’s own guidance.

5. APPLICABILITY DOMAIN
The substance is composed of aromatic structures and amine and groups, which are well represented within the structural analogues training data set.

6. ADEQUACY OF THE RESULT
The structural analogues are considered to adequately fall within the same domain to at least support a weight of evidence approach. The data set specifically includes aromatic carbon structures and structures with amine groups

Qualifier:

according to guideline

Guideline:

other: QSAR prediction using US EPA On-Line EPI Suite™ v4.11 model BCFBAF.

Deviations:

no

Principles of method if other than guideline:

The BCFBAF method classifies a compound as either ionic or non-ionic. Ionic compounds include carboxylic acids, sulfonic acids and salts of sulfonic acids, and charged nitrogen compounds (nitrogen with a +5 valence such as quaternary ammonium compounds). All other compounds are classified as non-ionic.

GLP compliance:

no

Specific details on test material used for the study:

Details on properties of test surrogate or analogue material (migrated information):
Not applicable - QSAR

Radiolabelling:

no

Details on sampling:

Not applicable - QSAR

Vehicle:

no

Details on preparation of test solutions, spiked fish food or sediment:

Not applicable - QSAR

Test organisms (species):

other: Not applicable - QSAR

Details on test organisms:

Not applicable - QSAR

Route of exposure:

other: Not applicable - QSAR

Test type:

other: Not applicable - QSAR

Water / sediment media type:

not specified

Hardness:

Not applicable - QSAR

Test temperature:

Not applicable - QSAR

pH:

Not applicable - QSAR

Dissolved oxygen:

Not applicable - QSAR

TOC:

Not applicable - QSAR

Salinity:

Not applicable - QSAR

Details on test conditions:

Not applicable - QSAR

Nominal and measured concentrations:

Not applicable - QSAR

Details on estimation of bioconcentration:

Please refer to QPRF attachment below

Key result

Type:

BCF

Value:

>= 94.69 - <= 629.9 L/kg

Basis:

other: QSAR

Calculation basis:

other: QSAR

Remarks on result:

other: range of values for three main components of UVCB substance

Details on kinetic parameters:

Not applicable - QSAR

Metabolites:

Not applicable - QSAR

Results with reference substance (positive control):

Not applicable - QSAR

Details on results:

Model assessment: Similar molecules found in the training set have experimental values that agree with the target compound predicted value.

Validity criteria fulfilled:

yes

Conclusions:

The range of BCF values for the three main components is 94.69 to 629.9 L/kg wet-wt. The substance is not considered to be bioaccumulative on the basis of the QSAR data developed.
The model is considered to be appropriate for assessment. Similar compounds with known experimental values in the training set were found. The accuracy of prediction for similar molecules found in the training set is good. The three most abundant structures present in the substance were assessed. The substance is not considered to be bioaccumulative on the basis of the QSAR data developed.

Executive summary:

It is understood that Annex XI, section 1.3 allows adaptation of the standard testing requirements by making use of (Q)SAR only if the following conditions are met:

(i) results are derived from a (Q)SAR  model whose scientific validity has been established,

(ii) the substance falls within the applicability domain of the (Q)SAR model,

(iii) results are adequate for the purpose of classification and labelling and/or risk assessment, and

(iv) adequate and reliable documentation of the applied method is provided.

 

Within the model used, the conditions (i) through (iv) are considered to be met for the US EPA On-Line EPI Suite™v4.11 model BCFBAF

 

The structures assessed with this model were deemed to mainly fall within the applicability domain of the model, and this is demonstrated within the relevant QPRF. The model is recognized, and referenced within ECHA’s own guidance. Due to the fact that QSAR is utilised, this study was categorised as a Klimisch level 2 study.

 

The range of BCF values for the three main components is 94.69 to 629.9 L/kg wet-wt. The substance is not considered to be bioaccumulative on the basis of the QSAR data developed.

Reference 2

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Study period:

28 April 2017

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Validated QSAR calculation method. A QPRF is attached. The model performs a read-across and provides a quantitative prediction of bioconcentration factor (BCF) in fish, given in log(L/kg). It is implemented inside the VEGA online platform, accessible at: http://www.vega-qsar.eu/.

Justification for type of information:

1. SOFTWARE: VEGA online platform, accessible at: http://www.vega-qsar.eu/

2. MODEL (incl. version number): BCF model (KNN/Read-Across) 1.1.0

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL:
Three most abundant structures in UVCB substance:
Diphenylamine: InChI=1S/C12H11N/c1-3-7-11(8-4-1)13-12-9-5-2-6-10-12/h1-10,13H
9,10-dihydro-9,9-dimethylacridine: InChI=1S/C15H15N/c1-15(2)11-7-3-5-9-13(11)16-14-10-6-4-8-12(14)15/h3-10,16H,1-2H3
N-phenyl-4-(propan-2-yl)aniline: InChI=1S/C15H17N/c1-12(2)13-8-10-15(11-9-13)16-14-6-4-3-5-7-14/h3-12,16H,1-2H3

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
No QMRF is available.. The model is recognized, and referenced within ECHA’s own guidance.

5. APPLICABILITY DOMAIN
The structural analogues are considered to adequately fall within the same domain to at least support a weight of evidence approach, however, two of the three components of the substance may be out of the applicability domain of the model.
For the component, diphenylamine, the prediction is reliable (it is based on experimental data).
For the components, N-phenyl-4-(propan-2-yl)aniline and 9,10-dihydro-9,9-dimethylacridine, the maximum error in prediction of similar molecules found in the training set has a moderate value, considering the experimental variability.

6. ADEQUACY OF THE RESULT
The structural analogues are considered to adequately fall within the same domain to at least support a weight of evidence approach. The data set specifically includes aromatic carbon structures and structures with amine groups

Qualifier:

according to guideline

Guideline:

other: QSAR prediction using BCF model (KNN/Read-Across) 1.1.0 (VEGA).

Deviations:

no

Principles of method if other than guideline:

The model performs a read-across and provides a quantitative prediction of bioconcentration factor (BCF) in fish, given in log(L/kg). It is implemented inside the VEGA online platform, accessible at: http://www.vega-qsar.eu/

The model performs a read-across on a dataset of 860 chemicals. This dataset has been made by Istituto di Ricerche Farmacologiche Mario Negri, merging experimental data from several reliable sources, including the original dataset of the CAESAR BCF model (note that experimental values may differ from the ones in the CAESAR BCF dataset, as this new dataset has been built including more sources).
The read-across is based on the similarity index developed inside the VEGA platform; the index takes into account several structural aspects of the compounds, such as their fingerprint, the number of atoms, of cycles, of heteroatoms, of halogen atoms, and of particular fragments (such as nitro groups).
The index value ranges from 1 (maximum similarity) to 0. On the basis of this structural similarity index, the three compounds from the dataset resulting most similar to the chemical to be predicted are taken into account: the estimated BCF value is calculated as the weighted average value of the experimental values of the three selected compounds, using their similarity values as weight.

GLP compliance:

no

Specific details on test material used for the study:

Details on properties of test surrogate or analogue material (migrated information):
Not applicable - QSAR

Radiolabelling:

no

Details on sampling:

Not applicable - QSAR

Vehicle:

no

Details on preparation of test solutions, spiked fish food or sediment:

Not applicable - QSAR

Test organisms (species):

other: Not applicable - QSAR

Details on test organisms:

Not applicable - QSAR

Route of exposure:

other: Not applicable - QSAR

Test type:

other: Not applicable - QSAR

Water / sediment media type:

not specified

Hardness:

Not applicable - QSAR

Test temperature:

Not applicable - QSAR

pH:

Not applicable - QSAR

Dissolved oxygen:

Not applicable - QSAR

TOC:

Not applicable - QSAR

Salinity:

Not applicable - QSAR

Details on test conditions:

Not applicable - QSAR

Nominal and measured concentrations:

Not applicable - QSAR

Details on estimation of bioconcentration:

Please refer to QPRF attachment below.

Key result

Type:

BCF

Value:

>= 194.98 - <= 389.05 L/kg

Basis:

other: QSAR

Calculation basis:

other: QSAR

Remarks on result:

other: range of values for three main components of UVCB substance

Details on kinetic parameters:

Not applicable - QSAR

Metabolites:

Not applicable - QSAR

Results with reference substance (positive control):

Not applicable - QSAR

Details on results:

Model assessment: Read-Across prediction is logBCF range = 2.29 to 2.59 for three most abundant structures in the substance. For the component, diphenylamine, the prediction is reliable (it is based on experimental data).
For the components, N-phenyl-4-(propan-2-yl)aniline and 9,10-dihydro-9,9-dimethylacridine, the maximum error in prediction of similar molecules found in the training set has a moderate value, considering the experimental variability.

Validity criteria fulfilled:

yes

Conclusions:

The range of BCF values for the three main components is 194.98 to 389.05 L/kg wet-wt. The substance is not considered to be bioaccumulative on the basis of the QSAR data developed.
For the component, diphenylamine, the read-across prediction appears to be reliable.
For the components, N-phenyl-4-(propan-2-yl)aniline and 9,10-dihydro-9,9-dimethylacridine, the maximum error in prediction of similar molecules found in the training set has a moderate value, considering the experimental variability.

Executive summary:

It is understood that Annex XI, section 1.3 allows adaptation of the standard testing requirements by making use of (Q)SAR only if the following conditions are met:

(i) results are derived from a (Q)SAR model whose scientific validity has been established,

(ii) the substance falls within the applicability domain of the (Q)SAR model,

(iii) results are adequate for the purpose of classification and labelling and/or risk assessment, and

(iv) adequate and  reliable documentation of the applied method is provided.

Within the model used, the conditions (i), (ii), (iii) and (iv) are considered to be met.

The structures assessed with this model were deemed to mainly fall within the applicability domain of the model, and this is demonstrated within the relevant QPRF.

For the component, diphenylamine, the prediction is reliable (it is based on experimental data).

For the components, N-phenyl-4-(propan-2-yl)aniline and 9,10-dihydro-9,9-dimethylacridine, the maximum error in prediction of similar molecules found in the training set has a moderate value, considering the experimental variability.

The model is recognized, and referenced within ECHA’s own guidance.Due to the fact that QSAR is utilised, this study was categorised as a Klimisch level 2 study.

 

The range of BCF values for the three main components is 194.98 to 389.05 L/kg wet-wt. The substance is not considered to be bioaccumulative on the basis of the QSAR data developed.

Description of key information

QSAR assessments were conducted using US EPA On-Line EPI Suite™ v4.11 model BCFBAF and VEGA BCF model (KNN/Read-Across) 1.1.0.

US EPA On-Line EPI Suite™ v4.0 model BCFBAF: The range of BCF values for the three main components is 94.69 to 629.9 L/kg wet-wt. The substance is not considered to be bioaccumulative on the basis of the QSAR data developed.

VEGABCF model (KNN/Read-Across) 1.1.0: The range of BCF values for the three main components is 194.98 to 389.05 L/kg wet-wt. The substance is not considered to be bioaccumulative on the basis of the QSAR data developed.

Key value for chemical safety assessment

BCF (aquatic species):

629.9 L/kg ww