Quaternary ammonium compounds, N,N,N'-tris(hydroxyethyl)-N,N'-dimethyl-N'-C16-18 (even numbered) and C18 unsatd., alkyltrimethylenedi-, bis(Me sulfates) (salts)

Bioaccumulation: aquatic / sediment

Link to relevant study record(s)

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

Justification for type of information:

QSAR prediction from an well known and acknowledged tool. See below under 'attachments' for applicability domain.

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

other: REACH guidance on QSARs: Chapter R.6. QSARs and grouping of chemicals

Principles of method if other than guideline:

1. Meylan,WM, Howard,PH, Boethling, RS et al, 1999. Improved method for estimating bioconcentration/bioaccumulation factor from octanol/water partition coefficient. Environ. Toxicol. Chem. 18(4):664-672.
2. Zhao C, Boriani E, Chana A, Roncaglioni A and Benfenati E, 2008. A new hybrid system of QSAR models for predicting bioconcentration factors
(BCF)", Chemosphere 73:1701–1707.
3. Hamelink, J. L., 1977. Current bioconcentration test methods and theory. In Aquatic Toxicology and Hazard Evaluation, edited by F. L. Mayer and J. L. Hamelink. West Conshohocken, PA ASTM STP.

Details on estimation of bioconcentration:

In absence of experimental data, the bioaccumulation potential (BCF) of the test substance was determined through computational method (such as BCFBAF v3.02 of EPIWEB v 4.11).

- Method details:
1. BCFBAF v3.01 program of EPISuite v 4.1:
- For the triglycerides, tocopherols and beta-sitosterols, the BCF values was estimated by using the derived QSAR estimation equation for Log Kow > 7.0 from EPISuite:
Log BCF = -0.49 Log Kow + 7.554 + Σ correction factors
(n = 35, r2 = 0.634, Q2 = 0.57, std dev = 0.538, avg dev = 0.396)
- For the fatty acids, the below equation for ionic compounds was used for the BCF estimation
Log BCF = 1.00 (Ionic; Log Kow dependent)

Key result

Type:

BCF

Value:

>= 70.8 L/kg

Basis:

whole body w.w.

Remarks on result:

other: BCF value estimated for the individual constituents using BCFBAF of EPISuite regression based method

Results:

Constituents	EPISuite BCFBAF Regression based (L/kg wet-wt)	EPISuite BCFBAF Arnot-Gobas based (L/kg wet-wt) upper trophic (including biotransformation rate estimates)	Domain evaluation
1	70.8	446.8	ID - MW, structural fragments, Log Kow
2	70.8	882.2	ID - MW, structural fragments, Log Kow
3	70.8	653.4	ID - MW, structural fragments, Log Kow

ID: in domain; MW: molecular weight

SMILES : CCCCCCCCCCCCCCCCN(H)(C)(CCO)CCCN(H)(C)(CCO)CCO
CHEM  :
MOL FOR: C27 H62 N2 O3
MOL WT : 462.81	ID	68.08	959.17
--------------------------------- BCFBAF v3.01 --------------------------------
Summary Results:
Log BCF (regression-based estimate): 1.85 (BCF = 70.8 L/kg wet-wt)
Biotransformation Half-Life (days) : 1.13 (normalized to 10 g fish)
Log BAF (Arnot-Gobas upper trophic): 2.66 (BAF = 452 L/kg wet-wt)
=============================
BCF (Bioconcentration Factor):
=============================
Log Kow (estimated) : 5.24
Log Kow (experimental): not available from database
Log Kow used by BCF estimates: 5.24	ID	-1.37	11.26
Equation Used to Make BCF estimate:
Log BCF = 1.85 (Ionic; 11 or more -CH2- groups)
Estimated Log BCF = 1.850 (BCF = 70.79 L/kg wet-wt)
===========================================================
Whole Body Primary Biotransformation Rate Estimate for Fish:
===========================================================
------+-----+--------------------------------------------+---------+---------
TYPE | NUM | LOG BIOTRANSFORMATION FRAGMENT DESCRIPTION | COEFF | VALUE
------+-----+--------------------------------------------+---------+---------
Frag | 1 | Linear C4 terminal chain [CCC-CH3]      | 0.0341 | 0.0341	ID	3
Frag | 3 | Aliphatic alcohol [-OH]                 | -0.0616 | -0.1847	ID	3
Frag | 3 | Methyl [-CH3]                           | 0.2451 | 0.7353	ID	12
Frag | 24 | -CH2- [linear]                          | 0.0242 | 0.5805	ID	28
Frag | 1 | Quaternary amine                         | 0.0000 | 0.0000
L Kow| * | Log Kow =  5.24 (KowWin estimate)       | 0.3073 | 1.6098
MolWt| * | Molecular Weight Parameter               |        | -1.1868
Const| * | Equation Constant                        |        | -1.5371
============+============================================+=========+=========
RESULT  |       LOG Bio Half-Life (days)           |        | 0.0512
RESULT  |           Bio Half-Life (days)           |        |  1.125
NOTE    | Bio Half-Life Normalized to 10 g fish at 15 deg C  |
============+============================================+=========+=========
Biotransformation Rate Constant:
kM (Rate Constant): 0.616 /day (10 gram fish)
kM (Rate Constant): 0.3464 /day (100 gram fish)
kM (Rate Constant): 0.1948 /day (1 kg fish)
kM (Rate Constant): 0.1095 /day (10 kg fish)
Arnot-Gobas BCF & BAF Methods (including biotransformation rate estimates):
Estimated Log BCF (upper trophic) = 2.650 (BCF = 446.8 L/kg wet-wt)
Estimated Log BAF (upper trophic) = 2.655 (BAF = 452 L/kg wet-wt)
Estimated Log BCF (mid trophic)  = 2.777 (BCF = 598 L/kg wet-wt)
Estimated Log BAF (mid trophic)  = 2.829 (BAF = 675.2 L/kg wet-wt)
Estimated Log BCF (lower trophic) = 2.813 (BCF = 650.7 L/kg wet-wt)
Estimated Log BAF (lower trophic) = 2.997 (BAF = 993.8 L/kg wet-wt)
Arnot-Gobas BCF & BAF Methods (assuming a biotransformation rate of zero):
Estimated Log BCF (upper trophic) = 4.056 (BCF = 1.138e+004 L/kg wet-wt)
Estimated Log BAF (upper trophic) = 5.416 (BAF = 2.604e+005 L/kg wet-wt)
SMILES : CCCCCCCCC=CCCCCCCCCN(H)(C)(CCO)CCCN(H)(C)(CCO)CCO
CHEM  :
MOL FOR: C29 H66 N2 O3
MOL WT : 490.86	ID	68.08	959.17
--------------------------------- BCFBAF v3.01 --------------------------------
Summary Results:
Log BCF (regression-based estimate): 1.85 (BCF = 70.8 L/kg wet-wt)
Biotransformation Half-Life (days) : 2.14 (normalized to 10 g fish)
Log BAF (Arnot-Gobas upper trophic): 2.95 (BAF = 896 L/kg wet-wt)
=============================
BCF (Bioconcentration Factor):
=============================
Log Kow (estimated) : 6.22
Log Kow (experimental): not available from database
Log Kow used by BCF estimates: 6.22	ID	-1.37	11.26
Equation Used to Make BCF estimate:
Log BCF = 1.85 (Ionic; 11 or more -CH2- groups)
Estimated Log BCF = 1.850 (BCF = 70.79 L/kg wet-wt)
===========================================================
Whole Body Primary Biotransformation Rate Estimate for Fish:
===========================================================
------+-----+--------------------------------------------+---------+---------
TYPE | NUM | LOG BIOTRANSFORMATION FRAGMENT DESCRIPTION | COEFF | VALUE
------+-----+--------------------------------------------+---------+---------
Frag | 1 | Linear C4 terminal chain [CCC-CH3]      | 0.0341 | 0.0341	ID	3
Frag | 3 | Aliphatic alcohol [-OH]                 | -0.0616 | -0.1847	ID	3
Frag | 3 | Methyl [-CH3]                           | 0.2451 | 0.7353	ID	12
Frag | 26 | -CH2- [linear]                          | 0.0242 | 0.6289	ID	28
Frag | 1 | Quaternary amine                         | 0.0000 | 0.0000
L Kow| * | Log Kow =  6.22 (KowWin estimate)       | 0.3073 | 1.9117
MolWt| * | Molecular Weight Parameter               |        | -1.2587
Const| * | Equation Constant                        |        | -1.5371
============+============================================+=========+=========
RESULT  |       LOG Bio Half-Life (days)           |        | 0.3295
RESULT  |           Bio Half-Life (days)           |        |  2.136
NOTE    | Bio Half-Life Normalized to 10 g fish at 15 deg C  |
============+============================================+=========+=========
Biotransformation Rate Constant:
kM (Rate Constant): 0.3246 /day (10 gram fish)
kM (Rate Constant): 0.1825 /day (100 gram fish)
kM (Rate Constant): 0.1026 /day (1 kg fish)
kM (Rate Constant): 0.05772 /day (10 kg fish)
Arnot-Gobas BCF & BAF Methods (including biotransformation rate estimates):
Estimated Log BCF (upper trophic) = 2.946 (BCF = 882.2 L/kg wet-wt)
Estimated Log BAF (upper trophic) = 2.952 (BAF = 896.2 L/kg wet-wt)
Estimated Log BCF (mid trophic)  = 2.953 (BCF = 896.5 L/kg wet-wt)
Estimated Log BAF (mid trophic)  = 3.462 (BAF = 2895 L/kg wet-wt)
Estimated Log BCF (lower trophic) = 2.994 (BCF = 986.7 L/kg wet-wt)
Estimated Log BAF (lower trophic) = 3.876 (BAF = 7519 L/kg wet-wt)
Arnot-Gobas BCF & BAF Methods (assuming a biotransformation rate of zero):
Estimated Log BCF (upper trophic) = 4.318 (BCF = 2.081e+004 L/kg wet-wt)
Estimated Log BAF (upper trophic) = 6.627 (BAF = 4.235e+006 L/kg wet-wt)
Arnot-Gobas BCF & BAF Methods (assuming a biotransformation rate of zero):
Estimated Log BCF (upper trophic) = 1.166 (BCF = 14.67 L/kg wet-wt)
Estimated Log BAF (upper trophic) = 1.178 (BAF = 15.07 L/kg wet-wt)
SMILES : CCCCCCCCCCCCCCCCCCN(H)(C)(CCO)CCCN(H)(C)(CCO)CCO
CHEM  :
MOL FOR: C29 H66 N2 O3
MOL WT : 490.86	ID	68.08	959.17
--------------------------------- BCFBAF v3.01 --------------------------------
Summary Results:
Log BCF (regression-based estimate): 1.85 (BCF = 70.8 L/kg wet-wt)
Biotransformation Half-Life (days) : 2.14 (normalized to 10 g fish)
Log BAF (Arnot-Gobas upper trophic): 2.95 (BAF = 896 L/kg wet-wt)
=============================
BCF (Bioconcentration Factor):
=============================
Log Kow (estimated) : 6.22
Log Kow (experimental): not available from database
Log Kow used by BCF estimates: 6.22	ID	-1.37	11.26
Equation Used to Make BCF estimate:
Log BCF = 1.85 (Ionic; 11 or more -CH2- groups)
Estimated Log BCF = 1.850 (BCF = 70.79 L/kg wet-wt)
===========================================================
Whole Body Primary Biotransformation Rate Estimate for Fish:
===========================================================
------+-----+--------------------------------------------+---------+---------
TYPE | NUM | LOG BIOTRANSFORMATION FRAGMENT DESCRIPTION | COEFF | VALUE
------+-----+--------------------------------------------+---------+---------
Frag | 1 | Linear C4 terminal chain [CCC-CH3]      | 0.0341 | 0.0341	ID	3
Frag | 3 | Aliphatic alcohol [-OH]                 | -0.0616 | -0.1847	ID	3
Frag | 3 | Methyl [-CH3]                           | 0.2451 | 0.7353	ID	12
Frag | 26 | -CH2- [linear]                          | 0.0242 | 0.6289	ID	28
Frag | 1 | Quaternary amine                         | 0.0000 | 0.0000
L Kow| * | Log Kow =  6.22 (KowWin estimate)       | 0.3073 | 1.9117
MolWt| * | Molecular Weight Parameter               |        | -1.2587
Const| * | Equation Constant                        |        | -1.5371
============+============================================+=========+=========
RESULT  |       LOG Bio Half-Life (days)           |        | 0.3295
RESULT  |           Bio Half-Life (days)           |        |  2.136
NOTE    | Bio Half-Life Normalized to 10 g fish at 15 deg C  |
============+============================================+=========+=========
Biotransformation Rate Constant:
kM (Rate Constant): 0.3246 /day (10 gram fish)
kM (Rate Constant): 0.1825 /day (100 gram fish)
kM (Rate Constant): 0.1026 /day (1 kg fish)
kM (Rate Constant): 0.05772 /day (10 kg fish)
Arnot-Gobas BCF & BAF Methods (including biotransformation rate estimates):
Estimated Log BCF (upper trophic) = 2.815 (BCF = 653.4 L/kg wet-wt)
Estimated Log BAF (upper trophic) = 2.952 (BAF = 896.2 L/kg wet-wt)
Estimated Log BCF (mid trophic)  = 2.953 (BCF = 896.5 L/kg wet-wt)
Estimated Log BAF (mid trophic)  = 3.462 (BAF = 2895 L/kg wet-wt)
Estimated Log BCF (lower trophic) = 2.994 (BCF = 986.7 L/kg wet-wt)
Estimated Log BAF (lower trophic) = 3.876 (BAF = 7519 L/kg wet-wt)
Arnot-Gobas BCF & BAF Methods (assuming a biotransformation rate of zero):
Estimated Log BCF (upper trophic) = 4.318 (BCF = 2.081e+004 L/kg wet-wt)
Estimated Log BAF (upper trophic) = 6.627 (BAF = 4.235e+006 L/kg wet-wt)
Arnot-Gobas BCF & BAF Methods (assuming a biotransformation rate of zero):
Estimated Log BCF (upper trophic) = 2.206 (BCF = 160.9 L/kg wet-wt)
Estimated Log BAF (upper trophic) = 2.287 (BAF = 193.5 L/kg wet-wt)

Validity criteria fulfilled:

not applicable

Conclusions:

Based on the BCF value estimation of individual constituents of test substance using BCFBAF v3.02 of EPIWEB v 4.11, the overall estimated BCFvalue for the test substance was considered to be 70.8 L/kg wet weight.

Executive summary:

The BCF value of test substance was estimated through use of QSAR program BCFBAF v3.02 of EPIWEB v 4.11. As the test substance is a UVCB/mixture of different constituents, the BCF values were determined for representative constituents. SMILES notations were used as the input parameters for the program/software. The BCF value estimated using regression based method of BCFBAF v.3.02 for the representative constituents was 70.8 L/kg wet weight (US EPA, 2021). Given that the predictions of the individual constituents were completely within domain, the uncertainty in the accuracy of the QSAR predictions are overall considered to be low.

Key value for chemical safety assessment

BCF (aquatic species):

70.8 L/kg ww

Additional information

The BCF value of test substance was estimated through use of QSAR program BCFBAF v3.02 of EPIWEB v 4.11. As the test substance is a UVCB/mixture of different constituents, the BCF values were determined for representative constituents.SMILES notations were used as the input parameters for the program/software. Based on the BCF value estimation of individual constituents of test substance using BCFBAF v3.02 of EPIWEB v 4.11, the overall estimated BCF values for the test substance was considered to be 70.8 L/kgww (US EPA, 2021). Given that the predictions of the individual constituents were not completely within domain for the structural fragments, the uncertainty in the accuracy of the QSAR predictions are overall considered to be moderate.