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Environmental fate & pathways

Bioaccumulation: aquatic / sediment

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Description of key information

The registration item and its relevant transformation products do not have a significant potential for bioaccumulation.


 


 

Key value for chemical safety assessment

Additional information

The test substance has a log Kow < 3 (0.42 -2.3 for representative structures of the UVCB, see chapter 4.7).Calculated solubilites in octanol of the three substructures range from 2.8 to 12.3 g/L (see chapter 4.9) and are therefore well below the "unlimited" solubility of oTDA-EO-PO in water. Therefore, bioaccumulation is not expected. This assumption was confirmed by different QSAR calculations.


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 polymer with ethoxylated and propoxylated components no purity (% w/w) can be stated. Therefore, the three representative chemical structures with three representative sizes (large, medium and small) were determined:



  1. Constituent 1 (CC(O)CNc1ccc(C)cc1NCCO), small size

  2. Constituent 2 (CC(CN(CCOCC(C)O)c1ccc(C)cc1N(CCOCC(C)O)CCOCC(C)OCC(C)O)OCC(C)O), medium size

  3. Constituent 3 (CC(CN(CCOCC(C)OCC(C)O)c1ccc(C)cc1N(CCOCC(C)OCC(C)O)CC(C)OCC(C)OCC(C)O)OCC(C)OCC(C)O), large size


 According to Regulation (EC) 1907 (2006) Annex IX, Section 9.3.2, Column 2, a study on bioaccumulation does not need to be conducted as the substance has a low potential for bioaccumulation (log Kow ≤3). However, no experimental data are available in order to assess the bioaccumulation potential of oTDA-EO-PO.


Therefore, in order to assess the biodegradation potential of oTDA-EO-PO (CAS 67800-94-6) a weight-of-evidence approach with the representative constituents was performed. Due to the lack of the experimental data for the constituents, the assessment of bioaccumulation is based on one QSAR model of CATALOGIC, three QSAR models of EPI Suite (BCFBAF) and three QSAR models 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 = within the Applicability Domain of the model)


 









































































































Model



Constituent 1



AD



Constituent 2



AD



Constituent 3



AD



 



BCF [L/kg]



 



BCF [L/kg]



 



BCF [L/kg]



 



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



186



No



2.63



No



Not calculated



No



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



1.03



Yes



0.96



Yes



1.37



No



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



1.4



Yes



1.26



Yes



3.55



Yes



CAESAR v2.1.14 (VEGA v1.1.3)



2



No



0.06



No



0.06



No



Meylan v1.0.3 (VEGA v1.1.3)



3



No



3



No



40



No



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



3.2



Yes



3.2



Yes



2.1



Yes



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



2.88



No



2.45



No



2.7



No



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



12.6



No



11.7



No



20



No



T.E.S.T. v4.2.1 (US EPA, 2016)



3.61



Yes



3.62



Yes



4.47



Yes



 


Considering all models applied constituents of the registration item are estimated to have BCF values range between 0.06 and 186 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 2 and 3 are higher than the critical value (19802 and 22.332 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 2.1 and 3.2. Using the Arnot-Gobas method including biotransformation, the BCF for the upper trophic level was estimated to be in the range between 0.96 and 1,37. (BASF SE, 2019). The constituents 1 and 2 were within the applicability domain of the Meylan and Arnot & Gobas models. The Constituent 3 was not within the applicability domain of Arnot & Gobas model.


- VEGA v1.1.3. – BCF estimation models BCF 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 constituents. The estimation models calculated for the constituents BCF values being in the range between 2.63 and 186 L/kg. The calculation of the BCF with KNN/Read-Across model was not possible for the constituent 3. However, all substances were not within the applicability domains of the calculation models.


- T.E.S.T. v4.2.1 (US EPA, 2016): The model is validated using statistical external validation using separate training and test data sets. The Consensus method averages the reasonable results from all applicable methods of T.E.S.T.: hierarchical clustering, single model, group contribution, FDA, and nearest neighbor. Regarding CAS 67800-94-6 the predicted BCF values from the Consensus method ranged from 3.6 to 4.5 L7kg (BASF SE, 2020). The confidence in the results is low and the substance is within the applicability domain of the model.


 


Hence, based on the available calculated data from the weight-of-evidence approach with main constituents, it is considered to be unlikely that the (CAS 67800-94-6) accumulates in aquatic organisms.


Assessment of relevant metabolites:


CATALOGIC BCF base-line model v03.10 (OASIS Catalogic v5.13.1) predicted no metabolites for the constituents.


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 of organisms and the molecular size of the target substance that additionally reduce the BCF, it can be concluded that the bioaccumulation of the substance in organisms is unlikely.