1,3,5-Triazine-2,4,6-triamine, N2,N2'-1,6-hexanediylbis[N4,N6-dibutyl-N2,N4,N6-tris(2,2,6,6-tetramethyl-4-piperidinyl)-

Endpoint summary

Description of key information

The bioaccumulation potential of the compound was assessed in a weight of evidence approach taking different QSAR calculations as well as physical-chemical parameters into account.

The following QSAR estimation tools were used.

-      OASIS Catalogic v5.11.19; BCF base-line model v.02.09

-      EPISuite v4.11; BCFBAF v3.01

o   Regression based estimate

o   Arnot-Gobas method including biotransformation rate estimates upper trophic level

As the molecule is too big for the tools, it was split in half for the tools. The underlying assumption is that the entire molecule is too big to accumulate and calculating the BCF for half of the molecule is therefore regarded as worst case condition. The smaller molecule is expected to easier pass biological cell membranes compared to the entire molecule. The calculations used the modeled logKow. The following molecule was considered:

CCCCN(Cc1nc(nc(n1)N(CCCC)C2CC(C)(C)NC(C)(C)C2)N(CCC)C3CC(C)(C)NC(C)(C)C3)C4CC(C)(C)NC(C)(C)C4

 

Table 1: Summary of the QSAR models and the results.

Model	BCF	Remarks
OASIS Catalogic v5.11.19; BCF base-line model v.02.09	7.8	·        In parametric domain. ·        69.57% correct fragments in structural domain. ·        In mechanistic domain.
EPISuite v4.11; BCFBAF v3.01	38.1 L/kg	regression-based estimate; in domain
	3.092 L/kg	Arnot-Gobas; including biotransformation rate estimates; upper trophic; outside of domain, result may be less accurate

 

 

OASIS Catalogic revealed a BCF of 7.8 with all mitigating factors applied. Out of the five mitigating factors taken into account by the model, molecular size and metabolism have the biggest influence on the result. Without considering any mitigating factor a BCF-max of 342.4 was estimated. The compound was inside the parametric and the mechanistic domain but only 69.57% of the fragments were found in correctly predicted training set compounds. However, the result is regarded as suitable in a weight of evidence approach.

The BCFBAF model integrated in the US EPA’s EPISuite encompasses two models. The regression based estimation according to the works of Meylan delivered a BCF of 38.1 with a calculated logKow of 9.91. The compound is inside of the applicability domain of the model. The other model integrated in the BCFBAF tool is based on the works of Arnot and Gobas and additionally considers biotransformation. Three different trophic levels are accounted for. For the upper trophic level the BCF was determined to be 3.092. However, the compound is outside of the applicability domain of the model. The result was not considered in the weight of evidence approach.

In addition to the QSAR estimations further information was used. According to ECHA’s Guidance on Information Requirements and Chemical Safety Assessment, chapter R.11: PBT/vPvB assessment the aquatic BCF of a substance is probably lower than 2000 if the calculated logKow is higher than 10. The entire molecule has a calculated logKow of 21.13. Furthermore, the capacity to cross biological membranes is highly dependent on the size of molecule. ECHA’s R.11 guidance states an average maximum diameter of > 1.7 nm and a molecular weight of greater than 1100 g/mol as a sign that the compound is not B as it is too bulky to cross biological membranes. The entire molecule has a molecular weight of 1408.31 g/mol. The average maximum diameter of the entire molecule is not known as it did not fit into Catalogic but half of the molecule already has an average maximum diameter of 1.9 nm. It can therefore easily be assumed that the entire molecule is definitely larger than 1.7 nm as stated in ECHA’s guidance document. Moreover, under environmentally relevant pH conditions (4 to 9) the compound is positively charged. It is known that the capacity to cross biological membranes of charged compounds is highly reduced due to hydration in aqueous media.

In summary, the compound is not expected to significantly accumulate in organisms. The valid QSAR estimations are well below the PBT trigger value of 2000. Furthermore, the calculated logKow is highly above 10 which is a clear sign that the compound has a BCF below 2000. Furthermore, it is not expected that the compound can cross biological membranes due to its molecular size, weight and hydration.

No significant accumulation in organisms is expected.