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Environmental fate & pathways

Bioaccumulation: aquatic / sediment

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Reference
Endpoint:
bioaccumulation in aquatic species: fish
Type of information:
(Q)SAR
Adequacy of study:
key study
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
Qualifier:
according to
Guideline:
other: REACH Guidance on information requirements and chemical safety assessment Chapter R.6: QSARs and grouping of chemicals, OECD 305 ”Bioaccumulation in Fish: Aqueous and Dietary Exposure"
Principles of method if other than guideline:
The determination of the bioconcentration factor (BCF) was performed by the BCFBAF model (v3.01) within EpiSuite (v4.1). The model is based on the relationship between the octanol/water partition coefficient and the bioconcentration factor of the training set. In order to improve the performance of the model correction factors for certain structural fragments were applied. Octanol can be viewed as a reasonable surrogate phase for lipids and biological organisms.

The predicted BCF value has been validated against experimental studies using the OECD 305 guideline or equivalent.
GLP compliance:
no
Remarks:
Not applicable, (Q)SAR endpoint
Specific details on test material used for the study:
SMILES: CCCCN(CCCC)CN(CCCC)CCCC
Radiolabelling:
no
Remarks:
Not relevant, (Q)SAR study
Details on sampling:
Not applicable, in silico assessment
Vehicle:
no
Remarks:
Not applicable, in silico assessment
Details on preparation of test solutions, spiked fish food or sediment:
Not applicable, in silico assessment
Test organisms (species):
other: Data for the (Q)SAR training set were taken from several experimental studies using varying fish species.
Details on test organisms:
Not applicable, in silico assessment
Route of exposure:
aqueous
Remarks:
Data for the (Q)SAR training set were taken from several experimental studies using varying fish species with an aqueous route of exposure.
Justification for method:
other: (Q)SAR
Remarks:
REACH Regulation Article 13 & 25, in vivo testing should be used as a last resort and alternative test methods should be sought (e.g. QSAR). ECHAChapter R.11: PBT/vPvB assessment: Log Kow over 4.5 further assessment of bioaccumulation was required.
Test type:
other: Not applicable, in silico assessment
Water / sediment media type:
other: Not applicable, in silico assessment
Hardness:
Not applicable, in silico assessment
Test temperature:
Not applicable, in silico assessment
pH:
Not applicable, in silico assessment
Dissolved oxygen:
Not applicable, in silico assessment
TOC:
Not applicable, in silico assessment
Salinity:
Not applicable, in silico assessment
Conductivity:
Not applicable, in silico assessment
Details on test conditions:
Not applicable, in silico assessment
Nominal and measured concentrations:
Not applicable, in silico assessment
Reference substance (positive control):
not required
Remarks:
Not applicable, in silico assessment
Details on estimation of bioconcentration:
The determination of the bioconcentration factor (BCF) was performed by the BCFBAF model (v3.01) within EpiSuite (v4.1). The model is based on the relationship between the octanol/water partition coefficient and the bioconcentration factor of the training set. In order to improve the performance of the model correction factors for certain structural fragments were applied. Octanol can be viewed as a reasonable surrogate phase for lipids and biological organisms.

Descriptor values were assigned by the BCFBAF v3.01 model using CAS RN or SMILES descriptors already provided. The partition coefficient descriptor was assigned from a KREATiS high-accuracy (Q)SAR prediction (KREATiS, 2017; Project No. 000/BFS/1701(3)). The Log KOW used was 5.7. This is considered conservative in comparison to the embedded model within the BCFBAF model (KOWWIN v1.68), which derived a Log KOW of 5.14 for the substance.

Following classification of the constituent as either ionic or non-ionic by the model; the model applies regression methodology using an appropriate algorithm: by applying fragment contribution and correction factor application where applicable. For non-ionic substances the model then sequentially calculates an estimate the log BCF from the log Kow using:

1. For log Kow - 1.0 to 7.0 the algorithm is as follows:
Log BCF = 0.6598 x log Kow - 0.33 + Σ correction factors
2. For log Kow > 7.0 the algorithm is as follows:
Log BCF = -0.49 x log Kow + 7.554 + Σ correction factors
3. All constituents with a log Kow of less than 1.0 are assigned an estimated log BCF of 0.5.

The full description of the methodology is described in the corresponding QMRF named 'QMRF Title: BCFBAF v3.01 Bioconcentration Factor (BCF)' version 1.01; 01 September 2015. There are no transformations of units however anti-logarithmic conversions are made to log BCF predictions to generate the BCF estimates.


Key result
Type:
BCF
Value:
113 L/kg
Details on kinetic parameters:
Not applicable, in silico assessment
Metabolites:
Not applicable, in silico assessment
Results with reference substance (positive control):
Not applicable, in silico assessment
Details on results:
Not applicable, in silico assessment - BCF determiend to be 113 L/kg wet wt.
Reported statistics:
Not applicable, in silico assessment
Validity criteria fulfilled:
not applicable
Remarks:
QSAR derived endpoint
Conclusions:
The QSAR model meets the criteria set out in section 1.3 of Annex XI to REACH and can be considered a reliable endpoint.

The bioconcentration factor of N,N,N’,N’-tetrabutylmethylenediamine, estimated BCFBAF v3.01 (EpiSuite v4.1), was 113 L/kg wet-wt., for fish.

Executive summary:

The bioconcentration factor (BCF) of N,N,N’,N’-tetrabutylmethylenediamine was predicted using the BCFBAF model v3.01 (EpiSuite v4.1). The input for the model were the molecular structure (SMILES notation) and the (Q)SAR derived Log KOW for the constituent (Log KOW 5.7; Thams P., 2017 Report No. 000/BFS/KOW/17001). This is considered conservative in comparison to the embedded model within the BCFBAF model (KOWWIN v1.68), which derived a Log KOW of 5.14 for the substance.

The QSAR model meets the criteria set out in section 1.3 of Annex XI to REACH and can be considered a reliable endpoint.

The BCF was reliably predicted as 113 L/kg wet-wt., for fish.

Description of key information

Bioconcentration factor (BCF) = 113 L/kg wet-wt., BCFBAF v3.01, K Paul, 2018.

Key value for chemical safety assessment

BCF (aquatic species):
113 L/kg ww

Additional information

The bioconcentration factor (BCF) of N,N,N’,N’-tetrabutylmethylenediamine was predicted using the BCFBAF model v3.01 (EpiSuite v4.1). The input for the model were the molecular structure (SMILES notation) and the (Q)SAR derived Log KOWfor the constituent (Log KOW5.7; Thams P., 2017 Report No. 000/BFS/KOW/17001). This is considered conservative in comparison to the embedded model within the BCFBAF model (KOWWIN v1.68), which derived a Log KOW of 5.14 for the substance.

The QSAR model meets the criteria set out in section 1.3 of Annex XI to REACH and can be considered a reliable endpoint.

The BCF was reliably predicted as 113 L/kg wet-wt., for fish