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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 Catalogic v5.14.1.5: BCF baseline model.

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)

Catalogic v5.14.1.5: BCF baseline model, without mitigating factors

2673

Within the AD

Catalogic v5.14.1.5: BCF baseline model, incl. all mitigating factors

8.5

Within the AD

Log Kow = 10.13 (estimated, KOWWIN v1.68)

 

BASF SE, 2014

Catalogic v5.14.1.15: BCF baseline model, without mitigating factors

240

Within the AD

Catalogic v5.14.1.15: BCF baseline model, incl. all mitigating factors

6.46

Within the AD

 

- Catalogic v5.14.1.5 – BCF base-line model v.04.11: Several BCF calculations using the CATALOGIC v.5.14.1.5 BCF base-line model v04.11 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 8.5 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 240 to 6.5 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 6.5 -8.5 L/kg significant bioaccumulations is not to be expected in animal tissues.

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.

Assessment of relevant metabolites:

CATALOGIC 301C v11.16(OASIS Catalogic v5.14.1.5) 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.5.14.1.5 BCF base-line model v04.11) calculated the BCF values for the 33 predicted metabolites, described above. The BCF model (CATALOGIC v.5.14.1.5 BCF base-line model v04.11) 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: QSAR prediction for CAS 1860-26-0 (Piperazine) using CATALOGIC 301C v11.16 (OASIS CATALOGIC v5.14.1.5; metabolites with a quantity > 0.001 mol/mol parent after 28 d are highlighted by grey background and bold type; metabolite no: according to (Q)SAR model Catalogic v11.16)

#

Metabolite
(no)

Smiles

Quantity
(mol/mol parent)

LogKow

BOD prediction
(% after 28 d)

BCF including mitigating factors

PBT-Assessment
(ECHA disseminated substances)

parent

1

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

0.701

10.1

7%

6.9

1

26

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

0.056

7.0

4%

5.4

not listed

2

33

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

0.054

7.9

4%

5.8

not listed

3

16

CCCCC(CC)CN / 2-ethylhexylamine / CAS 104-75-6

0.041

2.7

40%

33.9

not PBT/vPvB

4

4

CCCCC(CC)C(O)=O / 2-ethylhexanoic acid / CAS 149-57-5

0.031

3.0

77%

5.5

not PBT/vPvB

5

25

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

0.031

3.2

14%

8.7

not listed

6

32

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

0.031

4.2

15%

20.4

not listed

7

5

CCCC=C(CC)C(O)=O / 2-ethylhex-2-enoic acid / CAS 5309-52-4

0.027

2.9

67%

13.5

not listed

8

6

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

0.024

1.4

66%

3.2

not listed

9

8

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

0.020

0.9

91%

3.2

not listed

10

2

CCCCC(CC)CNCC(CC)CCCC / Bis(2-ethylhexyl)amine / CAS 106-20-7

0.015

6.6

44%

871

not PBT/vPvB

11

3

CCCCC(CC)C=O / 2-ethylhexanal / CAS 123-05-7

0.010

2.7

78%

3.8

not listed

12

27

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

0.005

5.5

23%

4.8

not listed

13

28

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

0.005

5.5

13%

4.8

not listed

14

35

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

0.004

6.5

22%

5.2

not listed

15

36

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

0.004

6.5

13%

5.2

not listed

16

34

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

0.002

6.5

22%

5.2

not listed

17

37

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

1.17E-08

8.6

47%

n.a. 

n.a. 

18

11

CC(O)CC(O)=O

0

-0.5

100%

n.a. 

n.a. 

19

12

CC(=O)CC(O)=O

0

-1.0

100%

n.a. 

n.a. 

20

10

CC=CC(O)=O

0

0.9

100%

n.a. 

n.a. 

21

9

CCCC(O)=O

0

1.1

100%

n.a. 

n.a. 

22

24

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

0

4.7

16%

n.a. 

n.a. 

23

30

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

0

8.6

17%

n.a. 

n.a. 

24

20

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

0

5.7

23%

n.a. 

n.a. 

25

19

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

0

8.6

24%

n.a. 

n.a. 

26

18

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

0

8.7

24%

n.a. 

n.a. 

27

29

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

0

8.7

17%

n.a. 

n.a. 

28

31

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

0

5.7

16%

n.a. 

n.a. 

29

22

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

0

4.2

22%

n.a. 

n.a. 

30

23

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

0

3.6

22%

n.a. 

n.a. 

31

7

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

0

2.0

91%

n.a. 

n.a. 

32

21

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

0

7.0

23%

n.a. 

n.a. 

33

13

CC(O)=O

0

0.1

100%

n.a. 

n.a. 

n.a.– not assessed. Metabolites with a quantity < 0.001 mol/mol parent after 28 d are not considered being relevant for the PBT/vPvB assessment and, therefore their PBT/vPvB status and BCF value were not assessed.

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.