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Environmental fate & pathways

Bioaccumulation: aquatic / sediment

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Description of key information

Significant accumulation of the substance (represented by by its branched and linear isomers) 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 Di-tridecylamine, branched and linear (CAS 101012-97-9) (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.


 


Parent compound:


Di-tridecylamine, branched and linear (CAS 101012-97-9) is a mixture of (predominantly) di-alkyl amines with varying alkyl-chain length in a range between C24 and C27. The main fraction consists of isomers of di-tridecylamines (C26H55N). Secondary fractions were detected to have chain lengths of C13 and C39. The following structures and relative fractions were proposed:


 


Table 1: Composition of DTDA (CAS 101012-97-9) according to analytical report 17Y36412 (BASF SE, 2017)














































Isomers



Quantity



Secondary fraction: Isomers of tridecyl amines



 



Isomers of C13H29N



0.9 %



Main fraction: Homologues of Dialkyl amines



 



Isomers of C24H51N



< 0.1 %



Isomers of C25H53N



0.4 – 0.5 %



Isomers of C26H55N



92 – 94 %



Isomers of C27H57N



0.25 – 0.35 %



Secondary fraction: Homologues of trialkyl amines



 



Isomers of C39H79N and C39H81N



< 5.2 %



 


A study is not required for this tonnage band. However, data will be provided in order to discuss the bioaccumulation potential within the PBT assessment.


In order to assess the bioaccumulation potential of the mixture (CAS 101012-97-9), the BCF was calculated for representative linear and branched isomers with the BCF base-line model v4.11 of OASIS Catalogic v5.14.1.5.


 


Table 2: BCF values predicted using BCF base-line model v04.11 (November 2019; available in OASIS Catalogic v.5.14.1.5; AD = applicability domain)























































































Representative structures of isomers
(sorted by number of carbon atoms)



BCF values (considering all mitigating factors/ without considering mitigating factors)



 



linear



in AD



branched



in AD



Secondary fraction: Isomers of tridecyl amines



 



 



 



 



C13H29N



1549 / 7852



yes



661 / 6209



yes



Main fraction: Homologues of Dialkyl amines



 



 



 



 



C24H51N



7.4 / 107



yes



8.9 / 171



yes



C25H53N



7.2 / 51.2



yes



7.1 / 88.3



yes



C26H55N



7.1 / 27.2



yes



7.2 / 47.8



yes



C27H57N



7.1 / 16.9



yes



7.2 / 25.8



yes



Secondary fraction: Homologues of trialkyl amines



 



 



 



 



C39H79N



7.1 / 9.1



yes



7.1 / 9.2



no



C39H81N



7.1 / 9.1



yes



7.1 / 9.1



yes



 


Almost all structures were within the parametric, structural, mechanistic and metabolic applicability domain of the model (13 of 14 molecules). Only one molecule (C39H79N, branched) was out of the applicability domain of the model as it did not meet the requirements of the metabolic domain (87.5% fragments in correctly predicted training chemicals, 12.5% fragments not present in training set), but was to 100% within the other subdomains (parametric, structural, mechanistic domain). In addition, the BCF was very similar to the other predicted BCF values.


The BCF values as shown in Table 2 are predicted taking into consideration mitigating factors. In addition, BCF values without considering mitigating factors are presented. However, for the assessment of the bioaccumulation potential, only BCF values considering mitigating factors are relevant.


Molecular size and water solubility 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). In case of the representative structures of the Substance, the BCF of those molecules with up to 27 carbon atoms was reduced mainly by molecular size and metabolism. In case of the larger structures (C39), the BCF was mainly reduced by the water solubility. However, the mean diameter of these molecules is larger than the critical value as discussed by the PBT working group, thus reducing the bioaccumulation potential further.


All predicted BCF values, considering mitigating factors, are below the critical BCF of 2000; therefore, the representative structures do not fulfil the criteria of B nor vB substances (BCF < 2000 /kg). The majority of the structures (12 out of 14) yielded BCF values below 500 (7.1 to 8.9 L/kg) indicating that significant bioaccumulation is not to be expected. One structure has a BCF close to 500 L/kg (BCF = 661; C13H29N, branched). The maximum BCF was predicted for C13H29N, linear, which has a BCF of 1549 L/kg. However, it should be noted that both structures have a low typical concentration (< 0.9%); therefore, the overall bioaccumulation potential is not significant.


 


Therefore, it can be concluded that none of the representative components fulfil the criteria for B/vB substances. Significant accumulation of CAS 101012-97-9 in organisms is not to be expected.


 


 


Predicted metabolites of C26H55N linear and branched:


The biodegradability and the potentially forming metabolites of the Substance were predicted using the QSAR model CATALOGIC 301C v11.16 (December 2019; available in OASIS Catalogic v.5.14.1.5) for the isomer C26H55N, which represents the isomer with the highest percentage of the Substance (92 to 94%). In order to take account of the effect of linear and branched structures, a linear isomer (CAS 5910 -75 -8) and a highly branched molecule (no CAS, SMILES:CCCC(CNCC(CCC)CC(CC)CC(C)C)CC(CC)CC(C)C) were used for the prediction (see IUCLID Ch. 5.2.1). For detailed information of the bioaccumulation potential of the relevant metabolites of C26H55N branched, which have a critical combination of being not readily biodegradable (BOD < 60%) and have a logKow > 3 (highlighted by bold type in Table 4) the BCF was additionally calculated using the BCF base-line model v04.11 - November 2019 (OASIS CATALOGIC v5.14.1.5).


 


 


Table 3: QSAR prediction for CAS 101012-97-9 (isomer: C26H55N, linear) using CATALOGIC 301C v11.16 – December 2019 (OASIS CATALOGIC v5.14.1.5; only metabolites with a quantity > 0.001 mol/mol parent (> 0.1%) after 28 d are listed; BCF calculated using BCF base-line model v04.11 - November 2019 (OASIS CATALOGIC v5.14.1.5); metabolite no: according to (Q)SAR model Catalogic v11.16 – December 2019 (OASIS CATALOGIC v5.14.1.5))




























































#



Metabolite
No #



Name (CAS No., Smiles)



Quantity
(mol/mol parent)



BOD prediction
(% after 28 d)



LogKow



BCF     



parent



1



Tridecanamine, N-tridecyl-, branched and linear: C26H54-NH, linear (CCCCCCCCCCCCCNCCCCCCCCCCCCC)



0.0662



72



11.61



7.1



1



27



Tridecylamine (CAS 2869-34-3; CCCCCCCCCCCCCN)



0.27



73



5.26



1549     



2



51



3-(Tridecylammonio) propanoate (CCCCCCCCCCCCCNCCC(O)=O)



0.0997



76



2.266



4.68     



3



54



Ethylamine (CAS 75-04-7; CCN)



0.0340



63



-0.15



3.39     



4



52



N-Ethyl-1-tridecanamine (CAS 59570-06-8; CCCCCCCCCCCCCNCC)



0.0297



74



6.21



398         



 


The log Kow of the relevant metabolites and their BCF were predicted to assess their bioaccumulation potential (Table 3). The log Kow was > 3 for two of these metabolites indicating that bioaccumulation is possible; however, the predicted BCF were < 2000 L/kg with a maximum BCF of 1549. Three out of these four metabolites were within the applicability domain of the BCF model. The metabolite “CCN” was out of the AD; however, the substances log Kow is very low indicating no significant potential for bioaccumulation. Therefore, it can be concluded that these metabolites do not meet the criteria for B/vB substances.


 


 


Table 4: QSAR prediction for CAS 101012-97-9 (isomer: C26H55N, branched) using CATALOGIC 301C v11.16 – December 2019 (OASIS CATALOGIC v5.14.1.5; only metabolites with a quantity > 0.001 mol/mol parent (> 0.1%) after 28 d are listed; metabolites with a BOD < 60% (nRBD) and log Kow > 3 are highlighted by bold type; metabolite no: according to (Q)SAR model Catalogic v11.16 – December 2019 (OASIS CATALOGIC v5.14.1.5))
















































































































































































































































#



Metabolite
No #



Name (CAS No, Smiles)



Quantity
(mol/mol parent)



BOD prediction
(% after 28 d)



LogKow



BCF    



parent



1



Tridecanamine, N-tridecyl-, branched and linear: C26H54-NH, branched (CCCC(CC(CC)CC(C)C)CNCC(CCC)CC(CC)CC(C)C)



5.20E-05



51



11.17



7.2



1



16



CCC(CCCNCC(CC(CC)CC(C)C)C(O)=O)CC(C)C



0.1681



49



4.35



5.5



2



23



2-Ethyl-4-methylpentanoic acid (CAS 108-81-6; CCC(CC(C)C)C(O)=O)



0.1427



39



2.89



4.57



3



55



(2S,4S)-2-(Aminomethyl)-4-ethyl-6-methylheptanoic acid (CAS 849487-76-9; CCC(CC(C)C)CC(CN)C(O)=O)



0.1403



43



-0.38



3.47



4



24



(2Z)-2-Ethyl-4-methyl-2-pentenoic acid (CCC(=CC(C)C)C(O)=O)



0.1241



67



2.80



12.3



5



36



CCC(CCCN)CC(C)C



0.1148



43



3.63



107.15



6



25



 (2S,3S)-2-Ethyl-3-hydroxy-4-methylpentanoic acid (CAS 73199-02-7; CCC(C(O)C(C)C)C(O)=O)



0.1079



65



1.35



3.09



7



27



(2R,3S)-3-Hydroxy-4-methyl-2-vinylpentanoic acid (CAS 458523-92-7; CCC(C(=O)C(C)C)C(O)=O)



0.09375



56



0.84



3.09



8



15



CCC(CC(C)C)CC(CNCC(CC(CC)CC(C)C)C(O)=O)C(O)=O



0.06011



42



2.95



5.25



9



17



CCC(CCCNCCCC(CC)CC(C)C)CC(C)C



0.05012



47



8.37



16.21



10



8



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



0.01192



48



5.75



6.61



11



46



CCC(CC(C)C)CC(C(O)=O)C(O)=O



0.01037



67



2.46



4.07



12



39



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



0.007628



46



5.27



40.74



13



48



CCCC(CC(CC)CC(C)C)CN



0.007628



62



5.03



467.74



14



84



CCC(CC(C)C)CC(CNCCC(O)=O)C(O)=O



0.004622



46



-0.76



3.71



15



73



CCC(CC(C)C)CC(CNCC(CC(CC)CC(C)C(O)=O)C(O)=O)C(O)=O



0.002876



35



1.71



5.12



16



74



CCC(CC(C)C)CC(CNCC(CC(CC)C=C(C)C(O)=O)C(O)=O)C(O)=O



0.0025



38



1.63



4.79



17



85



CCC(CCCNCC(C(O)=O)C(O)=O)CC(C)C



0.002311



46



-0.76



3.72



18



75



CCC(CC(C)C)CC(CNCC(CC(CC)C(O)C(C)C(O)=O)C(O)=O)C(O)=O



0.002173



38



0.17



4.37



19



77



CCC(CC(C)C)CC(CNCC(CC(CC)C(=O)C(C)C(O)=O)C(O)=O)C(O)=O



0.001889



43



-0.34



4.37



20



78



CCC(CC(C)C)CC(CNCC(CC(CC)C(O)=O)C(O)=O)C(O)=O



0.001642



38



0.31



4.47



21



79



CCC(CC(C)C)CC(CNCC(C=C(CC)C(O)=O)C(O)=O)C(O)=O



0.001427



43



0.23



4.17



22



19



CCC(CCC(O)=O)CC(C)C



0.001318



52



3.87



8.32



23



80



CCC(CC(C)C)CC(CNCC(C(O)C(CC)C(O)=O)C(O)=O)C(O)=O



0.001241



43



-1.23



3.8



24



82



CCC(CC(C)C)CC(CNCC(C(=O)C(CC)C(O)=O)C(O)=O)C(O)=O



0.001078



48



-1.74



3.8



 


14 of the predicted metabolites for the branched isomer C26H55N have a log Kow < 3 (range: -1.7 to 2.9) as well as a low BCF (max. BCF = 5.25 L/kg). Six of these non-readily biodegradable metabolites (#8, #16, #17, # 19, #36, #39, Table 4) have a log Kow > 3; however, the BCF was predicted to be < 2000 (range: 5.5 to 107 L/kg). It should be noted that 3 (#8, #16, #39) out of these 6 metabolites were not within the applicability domain of the BCF base-line model. However, the deviation from the applicability domain is minimal. These metabolites were completely within the parametric, structural, and mechanistic subdomains. In case of the metabolic domain, 100% of the atom-centered fragments (ACF) were identified as fragments present in the training chemicals. More than 93% of the metabolites’ ACF were identified as “fragments in correctly predicted training chemicals” (93.3 to 96.3%) and only the remainder of the ACF were identified as “non-correctly predicted training chemicals” (3.7 to 6.7%). Therefore, the predicted BCF values can be regarded as sufficiently reliable for this screening assessment.