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Environmental fate & pathways

Bioaccumulation: aquatic / sediment

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Description of key information

Significant accumulation in organisms is not to be expected.

Key value for chemical safety assessment

Additional information

QSAR-disclaimer

In Article 13 of Regulation (EC) No 1907/2006, it is laid down that information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI (of the same Regulation) are met. Furthermore, according to Article 25 of the same Regulation testing on vertebrate animals shall be undertaken only as a last resort.

According to Annex XI of Regulation (EC) No 1907/2006 (Q)SAR results can be used if (1) the scientific validity of the (Q)SAR model has been established, (2) the substance falls within the applicability domain of the (Q)SAR model, (3) the results are adequate for the purpose of classification and labeling and/or risk assessment and (4) adequate and reliable documentation of the applied method is provided.

For the assessment of 2-ethyl-N,N-bis(2-ethylhexyl)hexylamine (CAS 1860-26-0) (Q)SAR results were used for aquatic bioaccumulation. The criteria listed in Annex XI of Regulation (EC) No 1907/2006 are considered to be adequately fulfilled and therefore the endpoint(s) sufficiently covered and suitable for risk assessment.

Therefore, and for reasons of animal welfare, further experimental studies on aquatic bioaccumulation are not provided.

Assessment: 

A log Kow of 10.13 was estimated for the uncharged molecule. In addition, based on water solubility (< 2 µg/L at 20°C and pH 5.9) and octanol solubility (ca. 900 g/L at 20°C), a log Kow value of > 8.7 at 20°C was calculated (BASF SE, rep. no.: 09L00246, 2010). Both values indicate potential for bioaccumulation. However, as described in Appendix R.11—1 Annex 1 “Indicators for limited bioconcentration for PBT assessment”, REACH Guidance Document R.11, based on the current limited knowledge (both with respect to measured Log Kow and BCFs), a calculated Log Kow of 10 or above is taken as an indicator for showing reduced bioconcentration. Therefore, the assessment of the bioaccumulation potential of the substance (CAS 1860-26-0) should be regarded as a worst-case scenario log Kow of 8.7 and a water solubility of 2 µg/L. Estimations of the BCF were performed with different calculation models. The results are evaluated in a weight-of-evidence approach.

Table. 1 BCF estimation data (AD = applicability domain)

Model

BCF (L/kg)

Remark

Log Kow = 8.7 (estimated, pH 5.9, 20 °C)

 

(BASF SE, rep. no.: 09L00246, 2010)

EPI Suite v4.11, BCFBAF v3.01: Meylan et al. (1997/1999)

495

Within the AD

EPI Suite v4.11, BCFBAF v3.01: Arnot-Gobas (2003): upper trophic level, incl. biotransformation of zero

26

Not within AD

EPI Suite v4.11, BCFBAF v3.01: Arnot-Gobas (2003): upper trophic level, incl. biotransformation

1251

Not within AD

Catalogic v5.13.1: BCF baseline model, without mitigating factors

2673

Within the AD

Catalogic v5.13.1: BCF baseline model, incl. all mitigating factors

8

Within the AD

Log Kow = 10.13 (estimated, KOWWIN v1.68

 

BASF SE, 2014

EPI Suite v4.11, BCFBAF v3.01: Meylan et al. (1997/1999)

98

Within the AD

EPI Suite v4.11, BCFBAF v3.01: Arnot-Gobas (2003): upper trophic level, incl. biotransformation of zero

3.4

Not within AD

EPI Suite v4.11, BCFBAF v3.01: Arnot-Gobas (2003): upper trophic level, incl. biotransformation

63

Not within AD

Catalogic v5.11.15: BCF baseline model, without mitigating factors

253

Within the AD

Catalogic v5.11.15: BCF baseline model, incl. all mitigating factors

7

Within the AD

US EPA TEST v4.2.1: Consensus method

163

Within the AD.

 

- Catalogic v5.13.1 – BCF base-line model v.03.10: Several BCF calculations using the CATALOGIC v.5.13.1 BCF base-line model v03.10 are available for tris-2-ethylhexylamine (CAS 1860-26-0). The BCF model calculates the BCF implicating the log Kow value and the water solubility. Furthermore, the influence of mitigating factors like ionization of the molecule, water solubility, size and metabolism are also considered by the model. Taking into account a calculated log Kow of 8.7 (BASF SE, 2010; report no.: 09L00246) and a measured water solubility of 0.002 mg/L (BASF SE, 2010; report no.: 09L00246), the BCF is reduced from 2673 to 8. Metabolism and molecular size and to a minor part also water solubility reduce the overall bioaccumulation. Taking into account a calculated log Kow of 10.1 (estimated with EPI Suite v4.11; BASF SE, 2014) and the measured water solubility of 0.002 mg/L, the BCF is reduced from 253 to 7 by the same mitigating factors.

In both cases the reduction of the BCF is mainly due to metabolism.

Besides metabolism also the low water solubility and the molecular size reduce the log BCF as estimated by the model. Both parameters are discussed within the literature whether certain threshold values are suitable as cut-off criteria for indication of limited bioaccumulation. Regarding molecular size, the PBT working group on hazardous substances discussed a maximum diameter of > 17.4 Å (Comber et al., 2006).The mean diameter of the test item is determined to be 16.5 Å. All in all, based on the predicted BCF of 7-8 L/kg significant bioaccumulations is not to be expected in animal tissues.

- EPISuite v4.11 - BCFBAFv3.01: According to Meylan et al. 1997/1999, a BCF value of 495 was estimated based on a log Kow of 8.7 and a water solubility of 2 µg/L. Using the Arnot-Gobas method including biotransformation, the BCF for the upper trophic level was estimated to be 26 (BASF SE, 2014). Using a log Kow of 10.1, the BCF values are 98 for the Meylan method and 3.4 for the Arnot-Gobas method (upper trophic level, biotransformation). The substance is within the applicability domain of the Meylan method, but as it appreciably ionizes at physiological relevant pH, it is not within the applicability domain of the Arnot-Gobas method; therefore the estimate may be less accurate.

- T.E.S.T. v4.1 (US EPA model): The Consensus method averages the reasonable results from all applicable models (<= 5). The model shows only results which are within the applicability domain. Based on a comparison of the mean absolute error between the entire dataset and a reduced dataset using only similar chemicals, the confidence in the results is evaluated. Following EPA, the Consensus method yields the best results in terms of prediction accuracy and coverage. Regarding the test item tris-2 -ethylhexylamine (CAS 1860-26-0), the BCF result of the Consensus method was 163 (BASF SE, 2019).

Following the calculated log Kow values of 10.13 (uncharged molecule) and >8.7 (estimation based on water and octanol solubility), bioaccumulation in organisms may not be excluded. However, according to the REACH Guidance Document R.11 (PBT Assessment), the BCF of substances with a log Kow of > 10 is probably lower than 2000 L/kg. The bioaccumulation is assessed based on a weight-of-evidence approach.

The different estimation models (CATALOGIC v5.13.1 BCF base-line model v2.08, BCFBAF v3.01 and T.E.S.T v4.2.1) calculated BCF values between 3.4 and 2673. The geometric mean was calculated based on environmentally relevant models which consider mitigating factors like biotransformation, molecular size and/or water solubility. In addition, only values from models was considered where the substance was within the applicability domain and the results seemed reliable.

Based on a log Kow of 8.7, the geometric mean of the BCF is 63 (BCFBAF – Meylan; BCF base-line model). Based on a log Kow of 10.1, the geometric mean of the BCF is slightly lower (BCF = 48; BCFBAF – Meylan; BCF base-line model, T.E.S.T. v4.2.1).

Assessment of relevant metabolites:

CATALOGIC 301C v11.15 (OASIS Catalogic v5.13.1) was used to predicted the ready biodegradability of the substance as well as to predict potential metabolites. The substance was completely within the applicability domain. The model predicted 33 metabolites, identifying 16 metabolites as relevant degradation products in terms of PBT/vPvB assessment, with an estimated quantity of ≥ 0.1% (equivalent to ≥ 0.001 mol/mol parent; for details see ‘Attached background material’ of the respective Endpoint Study Record). Nine metabolites have a log Kow > 3 and 7 metabolites have a log Kow ≤ 3. The log Kow of the relevant metabolites ranges from 0.9 to 7.9. The BCF model (CATALOGIC v.5.13.1 BCF base-line model v03.10) calculated the BCF values for the 33 predicted metabolites, described above. The BCF model (CATALOGIC v.5.13.1 BCF base-line model v03.10) calculates the BCF implicating the log Kow value and the water solubility. Furthermore, the influence of mitigating factors like ionization of the molecule, water solubility, size and metabolism are also considered by the model. Taking into account all mitigation factors the BCF values were reduced. Metabolism and molecular size and to a minor part also water solubility reduce the overall bioaccumulation. Overall the BCF values calculated for all relevant metabolites, except the relevant metabolite #2 (CCCCC(CC)CNCC(CC)CCCC), are < 500 L/kg indicating no significant accumulation in organisms. Considering the relevant metabolite #2 (CCCCC(CC)CNCC(CC)CCCC), the BCF value was estimated to be 631 L/kg including mitigations factors. This value is higher than 500 L/kg but it is lower than 2000 L/kg which is a criterion for “B” and “vB” substances. Based on the estimation data available for the modelled metabolites, all (relevant) metabolites of the substance are concluded to be “not B” and “not vB”.

 

 

 

 

Table. 1 The predicted metabolites for CAS 1860-26-0 from the CATALOGIC 301C v11.15 estimation model.

 

No 

Metabolite (no) 

  Smiles

Quantity

  LogKow

log BCF#

without mitigation##

log BCF#

combination of all factors##

BCF#

without mitigation##

BCF#

combination of all factors##

BOD

(% after 28 d)

parent

1

CCCCC(CC)CN(CC(CC)CCCC)CC(CC)CCCC

(mol/mol parent)

10.1

2.4

0.9

251

7.9

7

1

3

CCCCC(CC)C=O

1.01E-02

2.7

2.1

0.6

126

4.0

78

2

2

CCCCC(CC)CNCC(CC)CCCC

1.50E-02

6.6

4.5

2.8

31600

631

44

3

18

CCCCC(CC)CN(CC(CC)CCCC)CC(CC)CCCCO

9.61E-07

8.7

3.5

0.8

3160

6.3

24

4

29

CCCCC(CC)CN(CC(CC)CCCC)CC(CCCC)CCO

9.61E-07

8.7

3.5

0.9

3160

7.9

17

5

37

CCCCC(CC)CN(CC(CC)CCCC)C(O)C(CC)CCCC

1.17E-08

8.6

3.5

1.1

3160

12.6

47

6

4

CCCCC(CC)C(O)=O

3.12E-02

3.0

2.2

0.7

158

5.0

77

7

16

CCCCC(CC)CN

4.06E-02

2.7

2.1

1.6

126

39.8

40

8

19

CCCCC(CC)CN(CC(CC)CCCC)CC(CC)CCCC=O

9.61E-07

8.6

3.5

0.8

3160

6.3

24

9

30

CCCCC(CC)CN(CC(CC)CCCC)CC(CCCC)CC=O

9.61E-07

8.6

3.5

0.8

3160

6.3

17

10

5

CCCC=C(CC)C(O)=O

2.71E-02

2.9

2.2

1.0

158

10.0

67

11

20

CCCCC(CC)CN(CC(CC)CCCC)CC(CC)CCCC(O)=O

9.61E-07

5.7

4.2

0.9

15800

7.9

23

12

31

CCCCC(CC)CN(CC(CC)CCCC)CC(CCCC)CC(O)=O

9.61E-07

5.7

4.2

0.9

15800

7.9

16

13

6

CCCC(O)C(CC)C(O)=O

2.36E-02

1.4

1.3

0.6

20

4.0

66

14

21

CCCCC(CC)CN(CC(CC)CCCC)CC(CC)CC=CC(O)=O

9.61E-07

7.0

4.5

2.3

31600

200.0

23

15

32

CCCCC(CC)CN(CC(CC)CCCC)CC(O)(CCCC)CC(O)=O

3.08E-02

4.2

3.1

1.2

1260

15.8

15

16

13

CC(O)=O

7.71E-06

0.1

1.0

0.4

10

2.5

100

17

7

CCCC(O)=C(CC)C(O)=O

1.57E-06

2.0

1.6

0.6

39

4.0

91

18

22

CCCCC(CC)CN(CC(CC)CCCC)CC(CC)CC(O)CC(O)=O

9.61E-07

4.2

3.1

0.8

1260

6.3

22

19

33

CCCCC(CC)CN(CC(CC)CCCC)CC(=O)CCCC

5.41E-02

7.9

4.0

0.8

10000

6.3

4

20

8

CCCC(=O)C(CC)C(O)=O

2.05E-02

0.9

1.1

0.5

13

3.2

91

21

23

CCCCC(CC)CN(CC(CC)CCCC)CC(CC)CC(=O)CC(O)=O

9.61E-07

3.6

2.7

0.8

501

6.3

22

22

34

CCCCC(CC)CN(CC(CC)CCCC)CC(=O)CCCCO

2.24E-03

6.5

4.5

0.8

31600

6.3

22

23

35

CCCCC(CC)CN(CC(CC)CCCCO)CC(=O)CCCC

4.48E-03

6.5

4.5

0.8

31600

6.3

22

24

36

CCCCC(CC)CN(CC(CCCC)CCO)CC(=O)CCCC

4.48E-03

6.5

4.5

0.8

31600

6.3

13

25

9

CCCC(O)=O

2.72E-06

1.1

1.2

0.5

158

3.2

100

26

24

CCCCC(CC)CN(CC(CC)CCCC)CC(CC)CC(O)=O

9.61E-07

4.7

3.5

0.8

3160

6.3

16

27

10

CC=CC(O)=O

2.72E-06

0.9

1.1

0.5

13

3.2

100

28

25

CCCCC(CC)CN(CC(CC)CCCC)CC(O)(CC)CC(O)=O

3.08E-02

3.2

2.4

0.9

251

7.9

14

29

11

CC(O)CC(O)=O

2.72E-06

-0.5

1.0

0.3

10

2.0

100

30

26

CCCCC(CC)CN(CC(CC)CCCC)CC(=O)CC

5.62E-02

7.0

4.5

0.8

31600

6.3

4

31

12

CC(=O)CC(O)=O

2.72E-06

-1.0

1.0

0.4

10

2.5

100

32

27

CCCCC(CC)CN(CC(CC)CCCCO)CC(=O)CC

4.56E-03

5.5

4.1

0.7

12600

5.0

23

33

28

CCCCC(CC)CN(CC(CCCC)CCO)CC(=O)CC

4.56E-03

5.5

4.1

0.7

12600

5.0

13

  # BCF-estimate using CATALOGIC BFC base-line mode v.03.10 (OASIS CATALOGIC v5.13.1.156)) (input data: WS & log Kow: calculated by the model)

 ## Mitigating factors: acids, metabolism, phenols, molecular size, water solubility

(metabolites which are predicted at quantity >0.001 after 28 d are highlighted in grey and written in bold letters)

(no, metabolite no, smiles, quantity, log Kow, BOD prediction: according to (Q)SAR model CATALOGIC 301C v11.15 – July 2018 (OASIS CATALOGIC v5.13.1.156))

It can be concluded that based on the available estimated data for the substance itself along with its predicted metabolites bioacumulation of 2-ethyl-N,N-bis(2-ethylhexyl)hexylamine (CAS 1860-26-0) is not to be expected.