N,N,N-tri-C8-C10-alkyl-N-methyl-1-aminium sulfate

Bioaccumulation: aquatic / sediment

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source and target substances have similar toxicological properties because
• they are manufactured from similar or identical precursors under similar conditions
• they share structural similarities with common functional groups: quaternary ammonium and saturated or unsaturated alkyl chains

The read-across hypothesis is based on structural similarity of target and source substances. The target and source chemicals have a similar structure in that they are comprised of a hydrophobic (alkyl) and hydrophobic (positively charged ammonium) end. Due to this motif they form micelles (colloidal dispersions) and have surfactant properties.

This read-across hypothesis corresponds to scenario 2 of the Read-Across Assessment Framework (RAAF), ECHA, March 2017 - different compounds have qualitatively similar properties - of the read-across assessment framework i.e. properties of the target substance are predicted to be quantitatively equal to those of the source substance. Namely, the structurally similar source substances DTDMAC , DODMAC, and DHTDMAC predict the ecotoxicological properties of the target substance Quaternary ammonium compounds, tri-C8-C10-alkylmethyl, Me sulfates.

Based on available experimental data, including key physicochemical properties and data from short-term aquatic ecotoxicity studies, the read-across strategy is supported by a similar ecotoxicological profile of the substances.

Therefore, read-across from the existing ecotoxicity, environmental fate and toxicity studies conducted with the source substances is considered as an appropriate adaptation to the standard information requirements of the REACH Regulation for the target substance, in accordance with the provisions of Annex XI, 1.5 of the REACH Regulation.

A justification for read-across is attached to IUCLID section 13.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
See justification for read-across attached to IUCLID section 13.

3. ANALOGUE APPROACH JUSTIFICATION
See justification for read-across attached to IUCLID section 13.

4. DATA MATRIX
See justification for read-across attached to IUCLID section 13.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across: supporting information

GLP compliance:

no

Nominal and measured concentrations:

Nominal concentration tested = 20 µg/L

Type:

BCF

Value:

256 L/kg

Basis:

non-edible fraction

Time of plateau:

14 d

Calculation basis:

steady state

Remarks on result:

other: Conc.in environment / dose:20 µg/L - Well water

Type:

BCF

Value:

94 L/kg

Basis:

non-edible fraction

Time of plateau:

49 d

Calculation basis:

steady state

Remarks on result:

other: Conc.in environment / dose:23 µg/L - River water

Type:

BCF

Value:

32 L/kg

Basis:

whole body w.w.

Time of plateau:

14 d

Calculation basis:

steady state

Remarks on result:

other: Conc.in environment / dose:20 µg/L - Well water

Key result

Type:

BCF

Value:

13 L/kg

Basis:

whole body w.w.

Time of plateau:

49 d

Calculation basis:

steady state

Remarks on result:

other: Conc.in environment / dose:23 µg/L - River water

Elimination:

yes

Parameter:

other: 93% of the test item was depurated after 14d

Depuration time (DT):

14 d

Validity criteria fulfilled:

not applicable

Conclusions:

The BCF values for bluegill were very low in river water (13 L/kg wwt), and slightly higher in well water (32 L/kg wwt). The BCF river water of 13 L/kg wwt was used in the EU Risk Assessment DODMAC (EU, 2002).
The relatively higher values in well water, whether based on residues in inedible tissue or in whole body, indicate the reduced bioavailability of the surfactants in surface water.

Reference 2

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

(Q)SAR

Adequacy of study:

supporting 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 limited documentation / justification

Justification for type of information:

1. SOFTWARE
EpiSuite v4.11

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

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CCCCCCCCN(H)(C)(CCCCCCCC)CCCCCCCC
CCCCCCCCCCN(H)(C)(CCCCCCCCCC)CCCCCCCCCC

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: BCF
- Unambiguous algorithm:
Ionic compounds are predicted as follows:
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)
- Defined domain of applicability: The BCFBAF method classifies a compound as either ionic or non-ionic. Ionic compounds include charged nitrogen compounds (nitrogen with a +5 valence such as quaternary ammonium compounds).
- Appropriate measures of goodness-of-fit and robustness and predictivity:
- Mechanistic interpretation:

5. APPLICABILITY DOMAIN
Currently there is no universally accepted definition of model domain. However, users may wish to consider the possibility that bioconcentration factor estimates are less accurate for compounds outside the MW and logKow ranges of the training set compounds, and/or that have more instances of a given correction factor than the maximum for all training set compounds. It is also possible that a compound may have a
functional group(s) or other structural features not represented in the training set, and for which no fragment coefficient was developed; and that a compound has none of the fragments in the model’s fragment library. In
the latter case, predictions are based on molecular weight alone. These points should be taken into consideration when interpreting model results.

As quaternary ammonium compounds are represented in the training set and the molecular weight of C12-18 alkyldimethyl ammonium chloride (ranging from 229.45 to 790.54) is within the range covered by the training set (minimum MW: 68.08, maximum MW: 991.80), the substance lies in the applicability domain of the model. Although the longer chain derivatives are outside of the range of log Kow of the training set (minimum LogKow: -6.50, maximum LogKow: 11.26), the major part of the constituents is within the applicability domain.

6. ADEQUACY OF THE RESULT
The results are considered appropriate to support the read-across approach.

Principles of method if other than guideline:

prediction of bioaccumulation using EpiSuite v4.11, BCFBAF v3.01

GLP compliance:

no

Type:

BCF

Value:

70.79 L/kg

Basis:

whole body w.w.

BCFBAF Program (v3.01) Results:

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

SMILES : CCCCCCCCN(H)(C)(CCCCCCCC)CCCCCCCC

CHEM  :

MOL FOR: C25 H55 N1

MOL WT : 369.72

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

Summary Results:

 Log BCF (regression-based estimate): 1.85 (BCF = 70.8 L/kg wet-wt)

 Biotransformation Half-Life (days) : 40.2 (normalized to 10 g fish)

 Log BAF (Arnot-Gobas upper trophic): 5.60 (BAF = 3.94e+005 L/kg wet-wt)

 

Log Kow (experimental): not available from database

Log Kow used by BCF estimates: 8.13

 

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 | 3 | Linear C4 terminal chain [CCC-CH3]      | 0.0341 | 0.1024

 Frag | 4 | Methyl [-CH3]                           | 0.2451 | 0.9804

 Frag | 21 | -CH2- [linear]                          | 0.0242 | 0.5079

 Frag | 1 | Quaternary amine                         | 0.0000 | 0.0000

 L Kow| * | Log Kow =  8.13 (KowWin estimate)       | 0.3073 | 2.4991

 MolWt| * | Molecular Weight Parameter               |        | -0.9481

 Const| * | Equation Constant                        |        | -1.5371

============+============================================+=========+=========

  RESULT  |       LOG Bio Half-Life (days)           |        | 1.6046

  RESULT  |           Bio Half-Life (days)           |        |  40.24

  NOTE    | Bio Half-Life Normalized to 10 g fish at 15 deg C  |

============+============================================+=========+=========

 

Biotransformation Rate Constant:

 kM (Rate Constant): 0.01723 /day (10 gram fish)

 kM (Rate Constant): 0.009687 /day (100 gram fish)

 kM (Rate Constant): 0.005447 /day (1 kg fish)

 kM (Rate Constant): 0.003063 /day (10 kg fish)

 

Arnot-Gobas BCF & BAF Methods (including biotransformation rate estimates):

  Estimated Log BCF (upper trophic) = 2.681 (BCF = 479.9 L/kg wet-wt)

  Estimated Log BAF (upper trophic) = 5.596 (BAF = 3.94e+005 L/kg wet-wt)

  Estimated Log BCF (mid trophic)  = 2.829 (BCF = 674.4 L/kg wet-wt)

  Estimated Log BAF (mid trophic)  = 5.511 (BAF = 3.242e+005 L/kg wet-wt)

  Estimated Log BCF (lower trophic) = 2.874 (BCF = 748 L/kg wet-wt)

  Estimated Log BAF (lower trophic) = 5.454 (BAF = 2.842e+005 L/kg wet-wt)

 

Arnot-Gobas BCF & BAF Methods (assuming a biotransformation rate of zero):

  Estimated Log BCF (upper trophic) = 3.468 (BCF = 2938 L/kg wet-wt)

  Estimated Log BAF (upper trophic) = 7.062 (BAF = 1.152e+007 L/kg wet-wt)

 

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

SMILES : CCCCCCCCCCN(H)(C)(CCCCCCCCCC)CCCCCCCCCC

CHEM  :

MOL FOR: C31 H67 N1

MOL WT : 453.89

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

Summary Results:

 Log BCF (regression-based estimate): 1.85 (BCF = 70.8 L/kg wet-wt)

 Biotransformation Half-Life (days) : 275 (normalized to 10 g fish)

 Log BAF (Arnot-Gobas upper trophic): 4.01 (BAF = 1.03e+004 L/kg wet-wt)

 

Log Kow (experimental): not available from database

Log Kow used by BCF estimates: 11.08

 

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 | 3 | Linear C4 terminal chain [CCC-CH3]      | 0.0341 | 0.1024

 Frag | 4 | Methyl [-CH3]                           | 0.2451 | 0.9804

 Frag | 27 | -CH2- [linear]                          | 0.0242 | 0.6531

 Frag | 1 | Quaternary amine                         | 0.0000 | 0.0000

 L Kow| * | Log Kow = 11.08 (KowWin estimate)       | 0.3073 | 3.4047

 MolWt| * | Molecular Weight Parameter               |        | -1.1639

 Const| * | Equation Constant                        |        | -1.5371

============+============================================+=========+=========

  RESULT  |       LOG Bio Half-Life (days)           |        | 2.4396

  RESULT  |           Bio Half-Life (days)           |        |  275.1

  NOTE    | Bio Half-Life Normalized to 10 g fish at 15 deg C  |

============+============================================+=========+=========

 

Biotransformation Rate Constant:

 kM (Rate Constant): 0.002519 /day (10 gram fish)

 kM (Rate Constant): 0.001417 /day (100 gram fish)

 kM (Rate Constant): 0.0007966 /day (1 kg fish)

 kM (Rate Constant): 0.000448 /day (10 kg fish)

 

Arnot-Gobas BCF & BAF Methods (including biotransformation rate estimates):

  Estimated Log BCF (upper trophic) = 0.565 (BCF = 3.677 L/kg wet-wt)

  Estimated Log BAF (upper trophic) = 4.012 (BAF = 1.028e+004 L/kg wet-wt)

  Estimated Log BCF (mid trophic)  = 0.691 (BCF = 4.913 L/kg wet-wt)

  Estimated Log BAF (mid trophic)  = 3.682 (BAF = 4805 L/kg wet-wt)

  Estimated Log BCF (lower trophic) = 0.731 (BCF = 5.382 L/kg wet-wt)

  Estimated Log BAF (lower trophic) = 3.440 (BAF = 2756 L/kg wet-wt)

 

Arnot-Gobas BCF & BAF Methods (assuming a biotransformation rate of zero):

  Estimated Log BCF (upper trophic) = 0.903 (BCF = 7.994 L/kg wet-wt)

  Estimated Log BAF (upper trophic) = 4.557 (BAF = 3.609e+004 L/kg wet-wt)

Conclusions:

The BCF of Quaternary ammonium compounds, tri-C8-C10-alkylmethyl, Me sulfates was predicted to be 70.79 L/kg (Episuite v4.11, BCFBAF v3.01).

Description of key information

BCF = 13 L/kg (river water); read-across from DODMAC and DTDMAC

Key value for chemical safety assessment

BCF (aquatic species):

13 L/kg ww

Additional information

No experimental data on bioaccumulation are available for Quaternary ammonium compounds, tri-C8-C10-alkylmethyl, Me sulfates. Data are, however, available for the closely related source substances DTDMAC and DODMAC. A justification for read-across is attached to IUCLID section 13.

 

Lepomis macrochirus was exposed to 14C-DTDMAC for 49 days in a continuous flow-through system in river water and laboratory water with mean concentrations in the test period of 18 μg/L and 16 μg/L respectively (no solvent carrier, Lewis & Wee, 1983). The river water was sampled at Town River, Massachusetts, and contained 2-84 mg/L suspended solids, 0.04-0.59 mg/L (methylene blue active substances) MBAS and 10-15 mg/l disulfine blue active substances (DBAS) (pH = 6.4-7.7; total hardness = 14-38 mg/L CaCO3). In river water, BCFs of 13 L/kg in the whole body and 94 in the inedible tissue (viscera) were estimated based on measured concentrations. When laboratory water was used, the respective BCFs were 32 and 256 L/kg. In both waters DTDMAC did not concentrate to a significant degree in edible tissue (BCF of the fillets < 5 L/kg). In a depuration phase in well water 93% of the accumulated radioactivity was eliminated from the inedible tissues after 14 days.

Overall, these results demonstrated that testing cationic surfactants under more realistic conditions (in river water) give lower bioavailability compared to studies using laboratory water.

Based on these test data, it can be concluded that DTDMAC does not accumulate in fish.

Juvenile fish (Pimephales promelas) were exposed to DODMAC for 24 h under flow-through conditions, followed by a depuration period of 72 h. Without Humic acid, a BCF of 103.8 L/kg could be calculated based on the uptake rate constant (k1) of 1.35 mg/g x h and the depuration rate constant (k2) of 0.013 mg/g x h. With the addition of 1 mg/L and 6.8 mg/L Humic acid, the BCF was 37.5 and 2.8 L/kg, respectively.

 

Low bioaccumulation potential of Quarternary ammonium compounds, tri-C8-C10-alkylmethyl, Me sulfates is also predicted by QSAR. The BCF of the substance was predicted to be 70.79 L/kg (Episuite v4.11, BCFBAF v3.01).