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Environmental fate & pathways

Bioaccumulation: aquatic / sediment

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Description of key information

A significant accumulation in organisms is not 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.

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.

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.

Assessment:

The substance is an UVCB substance. In accordance with Annex IX, Section 9.3.2 and Section 9.2.1.2 the assessment of bioaccumulation or bioconcentration and biodegradation of each constituent and impurity present in concentrations at or above 0.1% (w/w) must be performed. Since the substance is a complex mixture of isomers and homologues components no purity (% w/w) can be stated. Therefore, the corrected area-% values of constituents were determined by gas chromatography with FID. The evaluated area-% values were corrected with the content of water.

The following five main constituents which concentrations at or above 10 area % along with two constituents with the highest and the lowest molecular weight were analytically determined:

1.    Constituent 1 (CCC(COC(=O)C=C)(COC(=O)C=C)COC(=O)C=C)

2.    Constituent 2 (CCC(COC(C)COC(=O)C=C)(COC(C)COC(=O)C=C)COC(=O)C=C)

3.    Constituent 3 (CCC(COCCOC(=O)C=C)(COC(C)COC(=O)C=C)COC(=O)C=C)

4.    Constituent 4 (CCC(COC(C)COC(=O)C=C)(COC(C)COC(=O)C=C)COC(C)COC(=O)C=C)

5.    Constituent 5 (CCC(COCCOC(=O)C=C)(COC(C)COC(=O)C=C)COC(C)COC(=O)C=C)

6.    Constituent 6 (CCC(COCCOC(=O)C=C)(COCCOC(=O)C=C)COC(C)COC(=O)C=C)

7.    Constituent 7 (CCC(COCCOCCOC(=O)C=C)(COC(C)COC(C)COC(C)COC(=O)C=C)COC(=O)C=C)

Constituent 2 and 3 were determined to have a concentration of 22.4 area %. Constituent 3, 4 and 5 were determined to have a concentration value of 19.9 area %. The constituent 1 has the lowest molecular weight of 296 g/mol and the concentration of 0.6 area %. The highest molecular weight was determined for the constituent 7 (547 g/mol) which concentration was at 2.9 area %.

Therefore, in order to assess the bioaccumulation potential of the substance (EC 601-566-7) a weight-of-evidence approach with seven constituents was performed. Due to the lack of the experimental data for the constituents, the assessment of bioaccumulation is based on one QSAR models of CATALOGIC, one QSAR model of BCFBAF and three QSAR model of VEGA.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.

The table below lists the applied (Q)SAR models, the estimated biodegradation rates and basic information on the applicability domain (AD) for the compound. Detailed information on the model’s results and the AD are given in the endpoint study records of IUCLID Chapter 5.2.1. The selected models comply with the OECD principles for (Q)SAR models.

The following table provides results for the seven main constituents of the substance: (AD = Applicability Domain)

Model

Constituent 1

Constituent 2

Constituent 3

Constituent 4

Constituent 5

Constituent 6

Constituent 7

AD

 

BCF [L/kg]

BCF [L/kg]

BCF [L/kg]

BCF [L/kg]

BCF [L/kg]

BCF [L/kg]

BCF [L/kg]

 

BCF KNN/Read-Across v1.1.0 (VEGA v1.1.3)

29

33.1

15.8

14.4

14.4

15

n.a.

No

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

4.22

6.24

4.05

6.39

4.24

3.57

3.43

No

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

78.7

151

58.4

209

80.9

31.5

27.1

No

CAESAR v2.1.14 (VEGA v1.1.3)

3

1

1

0.66

0.72

0.78

0.15

No

Meylan v1.0.3 (VEGA v1.1.3)

36

56

29

69

37

19

30

No

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

36

55.6

29.5

69.1

36.6

19.4

17.5

Yes

BCF baseline model v.02.09 (OASIS Catalogic v5.11.19): incl. mitigating factors

4.7

4.8

4.6

4.8

4.6

4.5

4.5

No

BCF baseline model v.02.09 (OASIS Catalogic v5.11.19): not considering mitigating factors

146

233

118

295

149

77.3

120

No

 

Considering all models applied constituents of the registration item are estimated to have BCF values range between 0.15 and 295 L/kg.

- 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 the substance. 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. Metabolism and molecular size and to a minor part also water solubility reduce the overall bioaccumulation. 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 average diameters of the molecules of the Constituents 4, 5, 6 and 7 are higher than the critical value (18063 - 22.492 Å) indicating the bioaccumulation potential of the substance possibly to be reduced as the molecules may pass less easily through cell membranes. All in all, based on the predicted BCF values significant bioaccumulation is not to be expected in animal tissues. The test substances don’t meet the structural domain requirements of the BCF baseline model. According to OECD 305 protocol, the transformation of the parent (i.e., parent quantity) is decisive for the effect of metabolism (i.e.. the reproduction of subsequent step is less critical for the prediction of BCF). Hence, the disappearance of parent could be assumed to be reflected adequately by the model

- EPISuite v4.11 - BCFBAFv3.01: According to Meylan et al. 1997/1999, the BCF values was estimated based on a log Kow and were in the range between 17.5 and 69.1. Using the Arnot-Gobas method including biotransformation, the BCF for the upper trophic level was estimated to be in the range between 27.1 and 209. (BASF SE, 2019). The substances were within the applicability domain of the Meylan and Arno t& Gobas models.

- VEGA v1.1.3. – BCF estimation modelsBCF KNN/Read-Across v1.1.0, CAESAR v2.1.14 and Meylan v1.0.3 were also used to calculate the BCF values for the seven constituents. The estimation models calculated for the constituents BCF values being in the range between 0.15 and 69 L/kg. The calculation of the BCF with KNN/Read-Across model was not applicable for the constituent 7. However, all substances were not within the applicability domains of the calculation models.

Hence, based on the available calculated data from the weight-of-evidence approach with main constituents, it is considered that the Laromer PO 33F (EC 601-566-7) is not expected to accumulate within aquatic organisms.

 

 

Assessment of relevant metabolites:

CATALOGIC BCF base-line model v03.10 (OASIS Catalogic v5.13.1)predicted for the constituents 32 metabolites, identifying all of them as relevant degradation products in terms of PBT/vPvB assessment, with an estimated quantity of ≥ 0.1% (for details see ‘Attached background material’ of the respective Endpoint Study Record).

From the 32 relevant metabolites 3 metabolites was identified for the constituent 1, 4 for the constituent 2, 5 for the constituent 3, 3 for the constituent 4, 4 for the constituent 5, 5 for the constituent 6 and 5 for the constituent 7.

All modelled degradation products of the test substances were estimated not to exhibit log Kow values of 4.5 (see Table 1). However, based on the available calculated log Kow values the predicted metabolites could not be considered as ‘’B’’ or ‘’vB’’, according to screening criterion for bioaccumulation (B/vB). The calculated log BCF values for the predicted metabolites range from 3.2 to 37 L/kg. Thus, they are clearly under 500, thereby not fulfilling the screening criteria for bioaccumulation (B/vB) as laid down in Section 3.1 of REACH Annex XIII.Based on the estimation data available for the modelled metabolites, all relevant metabolites of Laromer PO 33F are concluded to be “not B” and “not vB”.

Table 1.QSAR prediction for EC 601-566-7 using CATALOGIC BCF base-line model v03.10 – July 2018 (OASIS CATALOGIC v5.13.1; metabolites with a quantity > 0.001 mol/mol are highlighted by bold type;

#

Smiles

Quantity [mol/mol parent]

log Kow

BCF (max)

BCF (mitig. factors)

Constituent 1

[L/kg]

[L/kg}

1

CCC(COC(=O)C=C)(COC(=O)C=C)COC(=O)C=C (Parent)

2.2E-08

2.9

146

4.7

2

CCC(CO)(COC(=O)C=C)COC(=O)C=C

0.95

1.5

22

3.7

3

C=CC(O)=O

0.95

0.4

11

3.2

4

C=CC(=O)OCC(CCO)(COC(=O)C=C)COC(=O)C=C

0.05

1.4

20

3.9

 

Constituent 2

 

 

 

 

1

CCC(COC(C)COC(=O)C=C)(COC(C)COC(=O)C=C)COC(=O)C=C (Parent)

2.2E-08

3.1

233

4.8

2

CCC(CO)(COC(C)COC(=O)C=C)COC(C)COC(=O)C=C

0.32

1.8

31

3.7

3

C=CC(O)=O

0.95

0.4

11

3.2

4

CCC(COC(C)CO)(COC(C)COC(=O)C=C)COC(=O)C=C

0.63

1.8

31

3.7

5

CC(COC(=O)C=C)OCC(CCO)(COC(C)COC(=O)C=C)COC(=O)C=C

0.05

1.7

27

4.0

 

Constituent 3

 

 

 

 

1

CCC(COCCOC(=O)C=C)(COC(C)COC(=O)C=C)COC(=O)C=C (Parent)

2.2E-08

2.7

118

4.6

2

CCC(CO)(COCCOC(=O)C=C)COC(C)COC(=O)C=C

0.3

1.4

20

3.5

3

C=CC(O)=O

0.9

0.4

11

3.2

4

CCC(COCCOC(=O)C=C)(COC(C)CO)COC(=O)C=C

0.3

1.4

20

3.5

5

CCC(COCCO)(COC(C)COC(=O)C=C)COC(=O)C=C

0.3

1.4

20

3.5

6

CC(COC(=O)C=C)OCC(CCO)(COCCOC(=O)C=C)COC(=O)C=C

0.1

1.3

18

3.8

 

Constituent 4

 

 

 

 

1

CCC(COC(C)COC(=O)C=C)(COC(C)COC(=O)C=C)COC(C)COC(=O)C=C (Parent)

2.2E-08

3.3

295

4.8

2

CCC(COC(C)CO)(COC(C)COC(=O)C=C)COC(C)COC(=O)C=C

0.9

1.9

37

3.7

3

C=CC(O)=O

0.9

0.4

11

3.2

4

CC(COC(=O)C=C)OCC(CCO)(COC(C)COC(=O)C=C)COC(C)COC(=O)C=C

0.1

1.8

32

4.0

 

Constituent 5

 

 

 

 

1

CCC(COC(C)COC(=O)C=C)(COC(C)COC(=O)C=C)COC(C)COC(=O)C=C (Parent)

2.2E-08

3.3

149

4.6

2

CCC(COC(C)CO)(COC(C)COC(=O)C=C)COC(C)COC(=O)C=C

0.9

1.9

23

3.5

3

C=CC(O)=O

0.9

0.4

11

3.2

4

CC(COC(=O)C=C)OCC(CCO)(COC(C)COC(=O)C=C)COC(C)COC(=O)C=C

0.1

1.8

23

3.5

5

CC(COC(=O)C=C)OCC(CCO)(COCCOC(=O)C=C)COC(C)COC(=O)C=C

0.1

1.4

20

3.8

 

Constituent 6

 

 

 

 

1

CCC(COC(C)COC(=O)C=C)(COC(C)COC(=O)C=C)COC(C)COC(=O)C=C (Parent)

2.2E-08

3.3

149

4.6

2

CCC(COC(C)CO)(COC(C)COC(=O)C=C)COC(C)COC(=O)C=C

0.9

1.9

23

3.5

3

C=CC(O)=O

0.9

0.4

11

3.2

4

CC(COC(=O)C=C)OCC(CCO)(COC(C)COC(=O)C=C)COC(C)COC(=O)C=C

0.1

1.8

23

3.5

5

CC(COC(=O)C=C)OCC(CCO)(COCCOC(=O)C=C)COC(C)COC(=O)C=C

0.1

1.4

20

3.8

 

Constituent 7

 

 

 

 

1

CCC(COCCOCCOC(=O)C=C)(COC(C)COC(C)COC(C)COC(=O)C=C)COC(=O)C=C (Parent)

2.2E-08

2.7

121

4.5

2

CCC(CO)(COCCOCCOC(=O)C=C)COC(C)COC(C)COC(C)COC(=O)C=C

0.3

1.4

20

3.5

3

C=CC(O)=O

0.9

0.4

11

3.2

4

CCC(COCCOCCOC(=O)C=C)(COC(C)COC(C)COC(C)CO)COC(=O)C=C

0.3

1.4

20

3.5

5

CCC(COCCOCCO)(COC(C)COC(C)COC(C)COC(=O)C=C)COC(=O)C=C

0.3

1.4

20

3.5

6

CC(COC(C)COC(C)COC(=O)C=C)OCC(CCO)(COCCOCCOC(=O)C=C)COC(=O)C=C

0.1

1.3

18

3.7

Conclusion:

Summing up the available estimated data on the bioaccumulation potential of the parent constituents and their predicted metabolites evolving from bioaccumulation, and taking into consideration mitigation factors like metabolism by organisms and the molecular size of the target substance that additionally reduce the BCF, it can be concluded that significant bioaccumulation in organisms is not to be expected.