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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
Study period:
November 2017
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:
Data on bioaccumulation is only required according to Annex IX of Regulation (EC) No 1907/2006. However, a valid QSAR model was applied to estimate BCF for the PBT/vPvB assessment. This estimation refers to the active component (C-Quart) of the manufactured substance.
Principles of method if other than guideline:
BCF was estimated using the Meylan et al. method in the BCFBAF software (version 3.01) as implemented in U.S.EPA’s EpiSuite™. BCFBAF represents a well-documented, peer-reviewed model for estimating BCF and full model documentation is available in the help file of the software as well as in Meylan et al. (1999). The model documentation reports correlation coefficients (R2) of 0.83 and 0.82, respectively, for the training (N= 527) and the validation set (N=158). The standard deviations are reported to be 0.5 (training set) and 0.59 (validation set). The training set contained 61 ionic compounds and according to ECHA Guidance R.7c (Version 3.0, June 2017), the model is appropriate for estimation of BCF for ionised substances. The model is characterised by a wide applicability domain including ionic compounds and the model documentation specifically refers to ‘+5 valence’ such as quaternary ammonium compounds being covered by the model.
Meylan et al. (1999) described the estimation methodology for BCFWIN, an earlier version of BCFBAF. The regression methodology applied for BCFWIN was kept unchanged for BCFBAF. However, BCFBAF was improved compared to BCFWIN by using an updated and better evaluated BCF database for selecting training and validation datasets, namely the high quality BCF database resulting from work of Arnot and Gobas (2006). Arnot and Gobas developed and applied minimum requirements for 6 criteria of high relevance for BCF determination to select for acceptable data quality.
In brief, the model was developed by linear regression of log BCF against log KOW for the training set compounds. The algorithm classifies substances as non-ionic or ionic (carboxylic acids, sulfonic acids, quaternary ammonium compounds). Specifically for ionic substances, categorical BCF values according to the log KOW range are assigned based on an evaluation of 84 ionic compounds (including 7 quaternary ammonium compounds (i.e. compounds with nitrogen of +5 valence) by Meylan et al. (1999):
log BCF = 0.50 (log Kow < 5.0)
log BCF = 1.00 (log Kow 5.0 to 6.0)
log BCF = 1.75 (log Kow 6.0 to 8.0)
log BCF = 1.00 (log Kow 8.0 to 9.0)
log BCF = 0.50 (log Kow > 9.0)
Furthermore, if the number of -CH2- fragments in a molecule exceeds 10, the following equation is used based on the publication by Meylan et al. (1999):
Log BCF = 1.85 (Ionic; more than 10 -CH2- fragments)

References:
Arnot JA and Gobas FAPC, 2006. A review of bioconcentration factor (BCF) and bioaccumulation factor (BAF) assessments for organic chemicals in aquatic organisms. Environmental Reviews, 14, 257-297.
Meylan WM, Howard PH, Boethling RS, Aronson D, Printup H and Gouchie S, 1999. Improved method for estimating bioconcentration/bioaccumulation factor from octanol/water partition coefficient. Environmental Toxicology and Chemistry, 18, 664-672.
GLP compliance:
no
Specific details on test material used for the study:
Test material information refers to the active component, for which QSAR was applied.
SMILES protonated form: CC(O)C[N+](C)(C)CCCCCC[N+](C)(C)CC(C)O
SMILES used in EpiSuite™: CC(O)CN(C)(C)CCCCCCN(C)(C)CC(C)O
EpiSuite™ is unable to process protonated SMILES notations. Therefore, a transformed SMILES notation was entered, ensuring that the critical fragment (N 5+) is correctly identified.
Details on sampling:
Not relevant for calculation/estimation methods.
Details on preparation of test solutions, spiked fish food or sediment:
Not relevant for calculation/estimation methods.
Details on test organisms:
Not relevant for calculation/estimation methods.
Hardness:
Not relevant for calculation/estimation methods.
Test temperature:
Not relevant for calculation/estimation methods.
pH:
Not relevant for calculation/estimation methods.
Dissolved oxygen:
Not relevant for calculation/estimation methods.
TOC:
Not relevant for calculation/estimation methods.
Salinity:
Not relevant for calculation/estimation methods.
Conductivity:
Not relevant for calculation/estimation methods.
Details on test conditions:
Not relevant for calculation/estimation methods.
Nominal and measured concentrations:
Not relevant for calculation/estimation methods.
Key result
Type:
BCF
Value:
3.16 L/kg
Details on kinetic parameters:
Not relevant for calculation/estimation methods.
Metabolites:
Not relevant for calculation/estimation methods.
Results with reference substance (positive control):
Not relevant for calculation/estimation methods.
Details on results:
See below.
Reported statistics:
Not relevant for calculation/estimation methods.

BCFBAF calculates a log BCF of 0.50 (BCF = 3.16 L/kg wet weight), since log Kow is < 5.0 and the number of -CH2- fragments is below 10 (see above for details). This calculation is independent of the log Kow value (if log Kow < 5). As a consequence, an identical log BCF of 0.5 is predicted for the final log Kow (-7.45) and the highest log Kow value discussed in section 4.7 (-0.846).

The output of BCFBAF (v3.01) is:

==============================

SMILES : CC(O)CN(C)(C)CCCCCCN(C)(C)CC(C)O

CHEM :

MOL FOR: C16 H38 N2 O2

MOL WT : 290.49

--------------------------------- BCFBAF v3.01 --------------------------------

Summary Results:

Log BCF (regression-based estimate): 0.50 (BCF = 3.16 L/kg wet-wt)

Biotransformation Half-Life (days) : 0.000387 (normalized to 10 g fish)

Log BAF (Arnot-Gobas upper trophic): -0.05 (BAF = 0.893 L/kg wet-wt)

Log Kow (experimental): not available from database

Log Kow used by BCF estimates: -7.45

Equation Used to Make BCF estimate:

Log BCF = 0.50 (Ionic; Log Kow dependent)

Estimated Log BCF = 0.500 (BCF = 3.162 L/kg wet-wt)

Validity criteria fulfilled:
not applicable
Conclusions:
Log BCF is estimated to be 0.5 by the valid and well-documented BCFBAF model (v. 3.01).
Executive summary:

Log BCF was estimated with the Meylan et al. method of the BCFBAF software (v. 3.01), a valid well-documented model. The log BCF is estimated by BCFBAF to be 0.5.

Description of key information

Log BCF is estimated to be 0.5 and BCF is estimated to be 3.16 L/kg (BCFBAF model (v. 3.01), 2017).

Key value for chemical safety assessment

BCF (aquatic species):
3.16 L/kg ww

Additional information

Data on bioaccumulation is only required according to Annex IX of Regulation (EC) No 1907/2006. However, a valid QSAR model was applied to estimate BCF for the PBT/vPvB assessment.

The log BCF for the active component (C-Quart) of the manufactured substance was estimated with the Meylan et al. method of the BCFBAF software (v. 3.01), a valid well-documented model. The log BCF is estimated by BCFBAF to be 0.5 (RL2).