Reaction products of diphenylamine with nonene, branched

Bioaccumulation: aquatic / sediment

Description of key information

The constituents of this uvcb substance do not meet the criteria for bioaccumulation accoding to REACh. 

Key value for chemical safety assessment

BCF (aquatic species):

1 730 dimensionless

Additional information

The bioaccumulative potential of the substance was assessed in a weight of evidence approach including experimental data, several QSAR estimations and data on the molecular size and log Kow. The substance is an UVCB, therefore 3 probable structures were assessed by QSAR. The single results are summarized in the table below.

Overview on BCF Results

Model/endpoint	Monoalkylated (C9) DPA	Dialkylated (C9C9) DPA	Trialkylated (C9C9C9) DPA
SMILES	CCCC(C)CC(C)(C)c1ccc (Nc2ccccc2)cc1	CCCC(C)CC(C)(C)c1ccc (Nc2ccc(cc2)C(C)(C)CC(C)CCC)cc1	CCCC(C)CC(C)(C)c1ccc (Nc2ccc(C(C)(C)CC(C)CCC)cc 2C(C)(C)CC(C)CCC)cc1
Molecular weight Da	295	422	548
Episuite 4.11 (KOW v 1.68) logKow	7.6	11.9	16.17
Catalogic 5.11.19 (Bioaccumulation baseline model v2.09) BCF L/kg  Mitigating factors	831.76     Metabolism (0.5) and size (0.5)	7.58     Metabolism (0.6) and size (0.7)	7.76
BCFBAF v3.01, (regression-based estimate) BCF L/kg	6890	54.4	3.16
BCFBAF v3.01 including biotransformation, lower to upper trophic) BCF L/kg	1118 - 721.6	2.4 - 1.7	0.94- 0.89
Catalogic Diamax average	16.6Å	20Å	20.8Å
Experimental derived BCF	1730 L/kg

EXPERIMENTAL DATA

Experimental data on the C9 monoalkylated DPA (CAS 27177 -41 -9) are available.

This GLP study followed the procedures of the Chemical Substances Control Law of Japan and was performed with Cyprinus carpio as test species

(Mitsubishi Chemical Safety Institute 2000)

The exposure period was 42 days, the depuration period 42 days. The variations in the BCF on days 28, 35, and 42 were within 20%, indicating that the bioconcentration reached a steady state. The following BCF values were determined:

 

High exposure level:          0.10 mg/L            BCF  411             whole body w.w.

Low exposure level:           0.01 mg/L            BCF 1730           whole body w.w.

 

The low exposure level is in the solubility range of the substance. The BCF on whole body was 110-476 for the experiment at the high exposure level and 395-1870 for the experiment at the low exposure level. At depuration time 10 days the eliminated amount was 27%, at 20 days 66% and at 42 days 82% of the steady state concentration in the fish.

Dialkylated diphenylamine occurring as minor constituent in the test material could not be detected in fish indicating a lower bioaccumulation potential for these structures.

 

QSAR

The BCF base-line model integrated in Catalogic is a sophisticated model which takes into account different mitigating factors, i.e. acids, metabolism, phenols, size and water solubility. The three structures were inside the parametric and the mechanistic domains of the compound with 100% of the fragments of the target chemical being present in correctly predicted training chemicals. The result is regarded as reliable and suitable to be used in a weight of evidence approach together with the in vivo results. With mitigating factors applied the BCF is determined as 8 to 832 for these structures. Size and metabolism are the major mitigating factors for the representative structures.  

 

US EPA’s EPISuite includes the regression-based estimation and the Arnot-Gobas model which takes biotransformation processes into account. All three structures are within the applicability domain except dialkylated (C9C9) DPA and trialkylated (C9C9C9) DPA, which are within the molecular weight range but outside the log Kow range of both the regression-based estimation and the Arnot-Gobas model. The regression-based model predicted a BCF of > 2000 L/kg for the monoalkylated (C9) DPA. The Arnot-Gobas model predicted BCF value of 722 L/kg for the upper trophic level including biotransformation rate estimates and a BCF of 5810 with biotransformation rates of zero. As the values which are > 2000 are calculated without considering metabolism and biotransformation, these values are regarded as not relevant. However, from the results it can be concluded that the monoalkylated DPA represents the worst case regarding bioaccumulation potential. The EPISuite results were regarded as suitable in the weight of evidence approach.

 

INDICATIONS OF REDUCED BIOACCUMMULATION POTENTIAL

logKow and size

According to ECHA’s Guidance on Information Requirements and Chemical Safety Assessment chapter R.11 – PBT Assessment, compounds with an average maximum diameter of >1.7 nm together with molecular weight of greater than 1100 are unlikely to have a BCF of >2000. Although the three probable structures of the UVCB substance have a molecular weight of only 295 422 and 548g/mol the DiamMax-average ranges between 16 and 20.8 Angstrom. This indicates a limited bioavailability, especially for the dialkylated and trialkylated structures.

Furthermore, the aquatic BCF of a substance is probably lower than 2000 if the calculated logKow is higher than 10. The dialkylated structure has a calculated log Kow of > 11.9, whereas the trialkylated structure has a calculated log KOW of > 16.1.

Based on the QSAR data available, the monoalkylated (C9) DPA is better available than the di- and tri substituted DPA and represents a worst case regarding the bioaccumulation potential of these three structures.

 

Metabolism

The Arnot-Gobas model predicts significant biotransformation potential. In the OASIS BCF baseline v2.09 model metabolism is identified as main mitigating factor for reduced bioaccumulation.

 

Toxicological studies

The bioaccumulation potential for the UVCB substance is determined as low based on toxicological data (see IUCLID section 7.1 for further information).

 

Conclusion:

In summary, in a weight-of-evidence approach balancing different QSAR estimations and experimental data significant accumulation of the constituents of the UVCB substance in organisms are expected. However, all data on the constituents of the UVCB substance showed a BCF <2000. The monoalkylated constituent has BCF values > 2000 only based on the Meylan model. As this model does not consider metabolism, it can be anticipated that this model overestimates the bioaccumulation potential. This is supported by experimental data on the substance.

Considering the available experimental data and the QSAR data of the different models, the BCF based on experimental data is used as worst case to assess the bioaccumulation potential for monoalkylated (C9) DPA and used for the CSA: 1730 L/kg. Based on the available data dialkylated (C9C9) DPA and trialkylated (C9C9C9) DPA are not bioaccumulative and not very bioaccumulative.

Therefore, according to Annex XIII of regulation 1907/2006/EC and according to the Guidance on information requirements and chemical safety assessment Chapter R.11 (PBT assessment, May 2008) this UVCB substance and its constituents do not fulfil the criterion “bioaccumulative (B)” or “very bioaccumulative (vB)”.

 

 

 

 

 

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 the substance (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 bioaccumulation are not provided.