1,3,5-tris[[4-tert-butyl-3-hydroxy-2,6-xylyl]methyl]-1,3,5-triazine-2,4,6(1H,3H,5H)-trione

Endpoint summary

Description of key information

According to REACH Annex IX, bioaccumulation testing in aquatic species need not be conducted if the test material has a low potential for bioaccumulation or a low potential to cross biological membranes.

 

1,3,5-tris[[4-tert-butyl-3-hydroxy-2,6-xylyl]methyl]-1,3,5-triazine-2,4,6(1H,3H,5H)-trione is highly insoluble in water (< 0.00002 g/L). Therefore, the partition coefficient of the substance had to be estimated using QSAR rather than measured. The estimated log Kow is 15.28 (EPIWIN Software). The very high partition coefficient makes it very unlikely that the substance will be able to cross cell membranes. Another uptake mechanism than passive diffusion driven by hydrophobicity is not expected for the present substance. This is further supported by the lack of systemic toxicity in toxicity studies with mammals. 

 

Additionally, the potential for bioaccumulation was further investigated using different QSAR models. Although the predictions are more or less of good reliability, all results are presented. None of these models predict that the substance could have a bioaccumulation potential with the only model outputting reliable information predicting a BCF of 31.7 L/kg wet-weight (log BCF 1.501).

 

Software	Model	Prediction	In domain of applicability / Reliability
EPISuite v.4.11	BCFBAF model v3.01 1.Regression-based estimate 2.Arnot-Gobas BCF & BAF methods	1. Log BCF 0.5; BCF 3.16 L/kg ww 2. Biotransformation rate (kM) 0.00035 d (10g fish);  a) assuming biotransformation rate estimate: BCF upper trophic 0.893; BAF upper trophic 0.893; BCF mid trophic 0.9315; BAF mid trophic 0.9315; BCF lower trophic 0.9402; BAF lower trophic 0.9402 b) assuming a biotransformation rate of zero: BCF upper trophic 0.8934; BAF upper trophic 3.157	Out of domain (out of log Kow range, MW exceeds 600 g/mol)
T.E.S.T. v4.2.1	1.Consensus 2.Hierarchical clustering 3.Nearest neighbor	1. Log BCF 1.32; BCF 20.92 L/kg ww 2. Log BCF 0.22-2.99; BCF 1.65 - 971.69 L/kg ww 3. Log BCF 1.03; BCF 10.84 L/kg ww	Low reliability of the predictions (MAE precision > MAE sets) Out of domain for the other models in T.E.S.T.
ISIDA	Bioconcentration Factor	Log BCF 1.501 BCF 31.7 L/kg ww	In domain of 12/17 models Good reliability

 

ISIDA: Detailed information on the model for BCF can be found in F. Lunghini, G. Marcou, P. Azam, R. Patoux, M.H. Enrici, F. Bonachera, D. Horvath and A. Varnek, QSPR models for bioconcentration factor (BCF): are they able to predict data of industrial interest?, SAR QSAR Environ. Res. 30 (2019), pp. 507–524. The predictor tool is publicly available at http://infochim.u-strasbg.fr/cgi-bin/predictor_reach.cgi 

This model uses fragments as molecular descriptors and multiple algorithms to derive an estimation.

 

Conclusion

 

1,3,5-tris[[4-tert-butyl-3-hydroxy-2,6-xylyl]methyl]-1,3,5-triazine-2,4,6(1H,3H,5H)-trione has an estimated log Kow of 15.28 and predicted BCF values well below the 2000 threshold. It is generally accepted that substances with such a high log Kow are very unlikely to have the ability to cross cell membranes and therefore are very unlikely to accumulate in aquatic organisms (Guidance on IR&CSA, Chapter R.11). This is further supported by the lack of systemic toxicity in toxicity studies with mammals. 

 

Based on the information available and in accordance with the recommendations of Chapter R.7c of the Guidance on IR&CSA on applying a Weight-of-Evidence approach, it is concluded that the substance is not bioaccumulative or very bioaccumulative in aquatic organisms. The value of the only reliable QSAR prediction is used for the assessment, i.e. 31.7 L/kg ww.