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Bioaccumulation: aquatic / sediment

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Endpoint:
bioaccumulation: aquatic / sediment
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:
1. SOFTWARE
EPI Suite v4.11 Estimation Programs Interface Suite™ for Microsoft® Windows v 4.11. US EPA, United States Environmental Protection Agency, Washington, DC, USA.

2. MODEL (incl. version number)
BCFBAF v3.01, Arnot-Gobas method

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See “Test material information”

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached information on the model provided by the developer. Further information on the OECD criteria as outlined by the applicant is provided below under "Any other information of materials and methods incl. tables"

5. APPLICABILITY DOMAIN
See attached information and information as provided in "Any other information on results incl. tables".

6. ADEQUACY OF THE RESULT
See assessment of adequacy as outlined in the "Overall remarks, attachments" section.
Reference:
Composition 0
Qualifier:
according to
Guideline:
other: REACH Guidance on QSARs R.6
Principles of method if other than guideline:
- Software tool(s) used including version: EPI Suite v4.11
- Model(s) used: BCFBAF v3.01
Full reference and details of the used formulas can be found in:
1. Arnot JA, Gobas FAPC. 2003. A generic QSAR for assessing the bioaccumulation potential of organic chemicals in aquatic food webs. QSAR and Combinatorial Science 22: 337-345.
- Model description: see field 'Justification for non-standard information', 'Attached justification' and 'any other information on material and methods'
- Justification of QSAR prediction: see field 'Justific ation for type of information', 'Attached justification' and/or 'overall remarks'
GLP compliance:
no
Test material information:
Composition 1
Vehicle:
no
Test organisms (species):
other: Fish
Route of exposure:
other: aqueous and dietary
Test type:
other: calculation
Water / sediment media type:
natural water: freshwater
Details on estimation of bioconcentration:
BASIS FOR CALCULATION OF BCF
- Estimation software: EPI Suite v4.11, BCFBAF v3.01
- Result based on measured log Pow of: 7.25
Type:
BCF
Value:
63.25 L/kg
Basis:
whole body w.w.
Remarks on result:
other: including biotransformation, upper trophic
Type:
other: log BCF
Value:
1.801 dimensionless
Basis:
whole body w.w.
Remarks on result:
other: including biotransformation, upper trophic

For detailed information on the results please refer to the attached report.

Endpoint:
bioaccumulation in aquatic species, other
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification
Remarks:
The substance is not fully compliant with the applicability domain of the model. However, this calculation is used in a weight of evidence approach, in accordance to the REACh Regulation (EC) No 1907/2006, Annex XI General rules for adaptation of the standard testing regime set out in Annexes VII to X, 1.2. It is adequately documented and justified. For more detail see field `overall remarks, attachments´.
Justification for type of information:
1. SOFTWARE
Vega version 1.1.3

2. MODEL (incl. version number)
BCF Read-Across v1.1.0

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See “Test material information”

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached information on the model provided by the developer. Further information on the OECD criteria as outlined by the applicant is provided below under "Any other information of materials and methods incl. tables"

5. APPLICABILITY DOMAIN
See attached information and information as provided in "Any other information on results incl. tables".

6. ADEQUACY OF THE RESULT
See assessment of adequacy as outlined in the "Overall remarks, attachments" section.
Reference:
Composition 0
Qualifier:
according to
Guideline:
other: REACH Guidance on QSARs R.6
Principles of method if other than guideline:
- Software tool(s) used including version: Vega v1.1.3
- Model(s) used: BCF Read-Across version 1.1.0
Full reference and details of the used formulas can be found in:
Manganaro, A., Pizzo, F., Lombardo, A., Pogliaghi, A., Benfenati, E., 2016. Predicting persistence in the sediment compartment with a new automatic software based on the k-Nearest Neighbor (k-NN) algorithm. Chemosphere 144, 1624–1630.
- Model description: see field 'Justification for non-standard information', 'Attached justification' and 'any other information on Material and methods'
- Justification of QSAR prediction: see field 'Justification for type of information', 'Attached justification' and/or 'overall remarks'
GLP compliance:
no
Test material information:
Composition 1
Vehicle:
no
Test organisms (species):
other: Fish
Route of exposure:
aqueous
Test type:
other: calculation
Water / sediment media type:
natural water: freshwater
Details on estimation of bioconcentration:
BASIS FOR CALCULATION OF BCF
- Estimation software: VegaNIC version 1.1.3, BCF Read-Across version 1.1.0
Type:
other: log BCF
Value:
1.74 dimensionless
Basis:
whole body w.w.
Type:
BCF
Value:
54.95 L/kg
Basis:
whole body w.w.

For detailed information on the results please refer to the attached report.

Endpoint:
bioaccumulation in aquatic species, other
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification
Remarks:
Result is based on a calcualted log Pow but the substance has a measured log Pow of 7.25.
Justification for type of information:
1. SOFTWARE
Vega version 1.1.3

2. MODEL (incl. version number)
CAESAR v 2.1.14

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See “Test material information”

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached information on the model provided by the developer. Further information on the OECD criteria as outlined by the applicant is provided below under "Any other information of materials and methods incl. tables"

5. APPLICABILITY DOMAIN
See attached information and information as provided in "Any other information on results incl. tables".

6. ADEQUACY OF THE RESULT
See assessment of adequacy as outlined in the "Overall remarks, attachments" section.
Reference:
Composition 0
Qualifier:
according to
Guideline:
other: REACH Guidance on QSARs R.6
Principles of method if other than guideline:
- Software tool(s) used including version: Vega v1.1.3
- Model(s) used: CAESAR BCF Model version 2.1.14
Full reference and details of the used formulas can be found in:
Zhao, C., Boriani, E., Chana, A., Roncaglioni,A., Benfenati, E. A new hybrid system of QSAR models for predicting bioconcentration factors (BCF). Chemosphere (2008), 73, 1701-1707.
Lombardo A, Roncaglioni A, Boriani E, Milan C, Benfenati E. Assessment and validation of the CAESAR predictive model for bioconcentration factor (BCF) in fish. Chemistry Central Journal (2010), 4 (Suppl 1).
Todeschini R. and Consonni V., Molecular Descriptors for Chemoinformatics, Wiley-VCH, (2009).
- Model description: see field 'Justification for non-standard information', 'Attached justification' and 'any other information on Material and methods'
- Justification of QSAR prediction: see field 'Justification for type of information', 'Attached justification' and/or 'overall remarks'
GLP compliance:
no
Test material information:
Composition 1
Vehicle:
no
Test organisms (species):
other: Fish
Route of exposure:
aqueous
Justification for method:
minimised test method used to support BCF estimates based on QSAR
Test type:
other: calculation
Water / sediment media type:
natural water: freshwater
Details on estimation of bioconcentration:
BASIS FOR CALCULATION OF BCF
- Estimation software: Vega version 1.1.3, CAESAR v 2.1.14
- Result based on calculated log Pow of: 5.59
Type:
other: Log BCF
Value:
1.55 dimensionless
Basis:
whole body w.w.
Type:
BCF
Value:
35 L/kg
Basis:
whole body w.w.
Type:
other: Log BCF
Value:
2.06 dimensionless
Remarks on result:
other: Predicted BCF from sub-model 1 (HM)
Type:
other: Log BCF
Value:
1.51 dimensionless
Remarks on result:
other: Predicted BCF from sub-model 2 (GA)

For detailed information on the results please refer to the attached report.

Endpoint:
bioaccumulation in aquatic species, other
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification
Remarks:
The substance is not fully compliant with the applicability domain of the model. However, this calculation is used in a weight of evidence approach, in accordance to the REACh Regulation (EC) No 1907/2006, Annex XI General rules for adaptation of the standard testing regime set out in Annexes VII to X, 1.2. It is adequately documented and justified. For more detail see field `overall remarks, attachments´.
Justification for type of information:
1. SOFTWARE
Vega version 1.1.3

2. MODEL (incl. version number)
BCF Meylan Model v1.0.3

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See “Test material information”

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached information on the model provided by the developer. Further information on the OECD criteria as outlined by the applicant is provided below under "Any other information of materials and methods incl. tables"

5. APPLICABILITY DOMAIN
See attached information and information as provided in "Any other information on results incl. tables".

6. ADEQUACY OF THE RESULT
See assessment of adequacy as outlined in the "Overall remarks, attachments" section.
Reference:
Composition 0
Qualifier:
according to
Guideline:
other: REACH Guidance on QSARs R.6
Principles of method if other than guideline:
- Software tool(s) used including version: Vega v1.1.3
- Model(s) used: BCF Meylan Model version 1.0.3
Full reference and details of the used formulas can be found in:
Meylan W.M., Howard P.H., Boethling R.S. et al. Improved Method for Estimating Bioconcentration / Bioaccumulation Factor from Octanol/Water Partition Coefficient. 1999, Environ. Toxicol. Chem. 18(4): 664-672
- Model description: see field 'Justification for non-standard information', 'Attached justification' and 'any other information on Material and methods'
- Justification of QSAR prediction: see field 'Justification for type of information', 'Attached justification' and/or 'overall remarks'
GLP compliance:
no
Test material information:
Composition 1
Vehicle:
no
Test organisms (species):
other: Fish
Route of exposure:
aqueous
Justification for method:
minimised test method used to support BCF estimates based on QSAR
Test type:
other: calculation
Water / sediment media type:
natural water: freshwater
Details on estimation of bioconcentration:
BASIS FOR CALCULATION OF BCF
- Estimation software: Vega version 1.1.3, Meylan Model version 1.0.3
- Result based on calculated log Pow of: 8.63
Type:
BCF
Value:
1 264 L/kg
Basis:
whole body w.w.
Type:
other: Log BCF
Value:
3.1 dimensionless
Basis:
whole body w.w.

For detailed information on the results please refer to the attached report.

Endpoint:
bioaccumulation in aquatic species: fish
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
08 Feb - 05 Apr 1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Study performed comparable to the OECD 305 guideline from 1981. It is considered suitable as supportive information.
Reference:
Composition 0
Qualifier:
according to
Guideline:
other: “Bioconcentration Test of Chemical Substances in the Body of Fish and Shellfish” (Kanpogyo No. 5, Yakuhatsu No. 615, 49 Kikyoku No. 392).
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 305 C (Bioaccumulation: Test for the Degree of Bioconcentration in Fish)
Version / remarks:
1981
GLP compliance:
no
Test material information:
Composition 1
Radiolabelling:
no
Details on sampling:
- Sampling intervals/frequency for test organisms: Samples were taken every 2 weeks.
Vehicle:
yes
Details on preparation of test solutions, spiked fish food or sediment:
PREPARATION AND APPLICATION OF TEST SOLUTION (especially for difficult test substances)
- Method:
25 g of test substance and 100 g of caster oil HCO20 were added to 5 L of distilled water and dispersed with using desperser for preparing stock solution.
Test organisms (species):
Cyprinus carpio
Details on test organisms:
TEST ORGANISM
- Common name:
carp
- Length at study initiation (length definition, mean, range and SD):
9.9 cm (mean)
- Weight at study initiation (mean and range, SD):
24.8 g (mean)
Route of exposure:
aqueous
Test type:
flow-through
Water / sediment media type:
natural water: freshwater
Total exposure / uptake duration:
8 wk
Test temperature:
25 ± 2 °C
pH:
6.44 - 7.34
Dissolved oxygen:
6.45 - 8.35 ppm
Details on test conditions:
TEST SYSTEM
- Test vessel:
100 L glass aquaria
- Type of flow-through (e.g. peristaltic or proportional diluter):
proportional diluter
- Renewal rate of test solution (frequency/flow rate):
400 mL/min
- No. of organisms per vessel:
16
- No. of vessels per concentration (replicates):
2
- No. of vessels per control / vehicle control (replicates):
1

TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water:
dechlorinated water

RANGE-FINDING / PRELIMINARY STUDY
- Test concentrations: 1, 10, 100 ppm
- Results used to determine the conditions for the definitive study: No mortality was observed in a preliminary study after 48 h. Thus, the selected concentrations are justified.
Nominal and measured concentrations:
nominal: 0.1 and 1.0 ppm
measured: 0.098 - 0.10 ppm; 0.98 - 1.0 ppm
Reference substance (positive control):
no
Lipid content:
>= 1.1 - <= 2.4 %
Time point:
other: 2 weeks
Remarks on result:
other: Concentration 1
Lipid content:
>= 1.4 - <= 2.4 %
Time point:
end of exposure
Remarks on result:
other: Concentration 1
Lipid content:
>= 1.1 - <= 2 %
Time point:
other: 2 weeks
Remarks on result:
other: Concentration 2
Lipid content:
>= 1.8 - <= 1.9 %
Time point:
end of exposure
Remarks on result:
other: Concentration 2
Conc. / dose:
0.1 other: ppm
Temp.:
>= 23 - <= 27 °C
Type:
BCF
Value:
>= 6.1 - <= 12 dimensionless
Basis:
whole body w.w.
Calculation basis:
steady state
Conc. / dose:
1 other: ppm
Temp.:
>= 23 - <= 27 °C
Type:
BCF
Value:
< 14 dimensionless
Basis:
whole body w.w.
Calculation basis:
steady state
Remarks on result:
not measured/tested
Remarks on result:
not measured/tested

Table 1.Mean concentrations in test water for calculation of bioconcentration factors (ppm)

 

2 weeks

4 weeks

6 weeks

8 weeks

Concentration level No. 1

0.98

0.98

0.99

1.0

Concentration level No. 2

0.098

0.097

0.099

0.10

 

Table 2. Concentrations in test fish (ppm)

 

2 weeks

4 weeks

6 weeks

8 weeks

Concentration level No. 1

1.59

2.90

<1.28

<1.29

3.41

3.83

6.08

12.3

Concentration level No. 2

<1.26

<1.20

<1.09

<1.60

<1.24

<1.22

<1.42

<1.43

<: Concentrations below the limit of quantification.

 

Table 3. Bioconcentration factors

 

2 weeks

4 weeks

6 weeks

8 weeks

Concentration level No. 1

1.6

3.0

<1.3

<1.3

3.4

3.9

6.1

12

Concentration level No. 2

<13

<12

<11

<17

<13

<12

<14

<14

<: Bioconcentration factors calculated from concentrations (in the fish) below the limit of quantification.

Table 4. Lipid content (%)

 

2 weeks

4 weeks

6 weeks

8 weeks

Concentration level No. 1

1.1

2.4

1.3

1.7

2.2

1.6

1.4

2.4

Concentration level No. 2

2.0

1.1

6.6

5.4

1.8

2.3

1.8

1.9

 

Table 5: Validity criteria for OECD 305 (2012).

Criterion from the guideline

Outcome

Validity criterion fulfilled

The water temperature variation is less than ± 2°C, because large deviations can affect biological parameters relevant for uptake and depuration as well as cause stress to animals.

25 ± 2 °C

yes

The concentration of dissolved oxygen does not fall below 60% saturation.

6.45 - 8.35 ppm

yes

The concentration of the test substance in the chambers is maintained within ± 20% of the mean of the measured values during the uptake phase.

nominal: 0.1 and 1.0 ppm

measured: 0.098 - 0.10 ppm; 0.98 - 1.0 ppm

yes

The concentration of the test substance is below its limit of solubility in water, taking into account the effect that the test water may have on effective solubility

Yes, for exposure level 1 (0.1 ppm)

Partly yes

The mortality or other adverse effects/disease in both control and treated fish is less than 10% at the end of the test; where the test is extended over several weeks or months, death or other adverse effects in both sets of fish should be less than 5% per month and not exceed 30% in all. Significant differences in average growth between the test and the control groups of sampled fish could be an indication of a toxic effect of the test chemical.

Not reported

No conclusion can be reached.

Validity criteria fulfilled:
not specified
Remarks:
However, the validity criteria of todays standard method (OECD 305C) are mainly met.

Description of key information

2-(1,1-dimethylethyl)-6-[[3-(1,1-dimethylethyl)-2-hydroxy-5-methylphenyl]methyl]-4-methylphenyl acrylate (CAS 61167-58-6) is considered to have a low potential for bioaccumulation based on the available data.

Key value for chemical safety assessment

Additional information

The bioaccumulation potential of 2-(1,1-dimethylethyl)-6-[[3-(1,1-dimethylethyl)-2-hydroxy-5-methylphenyl]methyl]-4-methylphenyl acrylate (CAS 61167-58-6) was assessed in a weight-of evidence approach in accordance with Regulation (EC) No 1907/2006, Annex XI, 1.2.
One experimental study is available investigating the bioaccumulation potential of the test item in freshwater species Cyprinus carpio. The study was performed according to “Bioconcentration Test of Chemical Substances in the Body of Fish and Shellfish” (Kanpogyo No. 5, Yakuhatsu No. 615, 49 Kikyoku No. 392), which is equivalent or similar to OECD 305C (1981). Fish were exposed to the test item under flow-through conditions at concentrations of 0.1 and 1.0 ppm. Both nominal exposure concentrations remained within 20% of nominal during exposure. The exposure concentrations in fish as well as in test medium were monitored every 2 weeks until a total duration of the study of 8 weeks. After 8 weeks of exposure a BCF of ≥ 6.1 to ≤ 12 was calculated for the exposure concentration of 0.1 ppm, and a BCF of < 14 was determined at the concentration of 1 ppm (based on whole body wet weight). Even though this study was not performed according to today’s standard methods it provides important evidence that the substance has a low potential for bioaccumulation in fish.

This result is further supported by several QSAR estimations (Meylan Model v1.0.3, CAESAR v2.1.14, BCF Read-across v1.1.0 (KNN), and BCFBAF v3.01). The performance of the models is moderate to good and therefore all results are used in combination with the experimental data in a Weight-of-Evidence approach. The predictions of the CAESAR, BCFBAF v3.01 and KNN models are all in the same range of magnitude (BCF values from 35 to 63.25 L/kg). All models show that the substance has a low potential for bioaccumulation.

The model training set of both the CAESAR and the KNN models contain an experimental result from a very similar substance (CAS 119-47-1;6,6'-di-tert-butyl-2,2'-methylenedi-p-cresol; Similarity: 0.881) bearing an experimental BCF of 93.33 L/kg. This study result was considered reliable in the Substance Evaluation Conclusion document for this substance issued by the evaluating member state of Denmark (30. June 2017). Both models perform very good on this molecule resulting in BCF values of 35 and 55, respectively (see Table 1). These results strongly support the results of the experimental study performed with2-(1,1-dimethylethyl)-6-[[3-(1,1-dimethylethyl)-2-hydroxy-5-methylphenyl]methyl]-4-methylphenyl acrylate.
The BCFBAF v3.01 model resulted in a BCF of 63.25 L/kg (including biotransformation) for the upper trophic. This result is in line with the BCF resulting from the CAESAR and KNN model as well as the experimental study.
The Meylan Model v1.0.3 with a resulting BCF of 1264 L/kg is very likely to overestimate the bioaccumulation potential since the model only takes the log Pow into account for prediction of bioaccumulation. Even though the log Pow is the most important parameter to assess bioaccumulation via distribution from surrounding medium to fat tissue it does not take any metabolic fate, sterical hindrance or any other parameters limiting bioaccumulation into account. Furthermore the model performance is not optimal for substances with high log Pow values (>7). Thus, this model can be described as the most simple one from all applied QSAR models and the result should be taken into account with caution.

The following table summarizes the available data for bioaccumulation.

Table 1: Available data for bioaccumulation of 2-(1,1-dimethylethyl)-6-[[3-(1,1-dimethylethyl)-2-hydroxy-5-methylphenyl]methyl]-4-methylphenyl acrylate

Experimental Study/QSAR

Guideline/Model

Result

Reliability

Experimental

Equivalent to OECD 305C

BCF: ≥6.1 to < 14

RL2

QSAR

CAESAR v2.1.14

BCF: 35 L/kg

RL2, not completely in applicability domain

QSAR

BCF Read-Across v1.1.0 (KNN)

BCF: 54.95 L/kg

RL2, not completely in applicability domain

QSAR

BCFBAF v3.01

BCF: 63.25 L/kg

RL2, in applicability domain

QSAR

Meylan Model v1.0.3

BCF: 1264 L/kg

RL2, not completely in applicability domain

 

Based on all available information, 2-(1,1-dimethylethyl)-6-[[3-(1,1-dimethylethyl)-2-hydroxy-5-methylphenyl]methyl]-4-methylphenyl acrylate is considered to have a low potential for bioaccumulation.