2,5-thiophenediylbis(5-tert-butyl-1,3-benzoxazole)

Bioaccumulation: aquatic / sediment

Description of key information

The compound is not expected to significantly accumulate in organisms. 

Additional information

The bioaccumulative potential of EC 230-426-4 was assessed in a weight of evidence approach including several QSAR estimations and data on the molecular size.The single QSAR models and their results are summarized in the table below.

Model		BCF	LogBCF	Remarks
Catalogic v5.11.15		7.08	0.85	all mitigating factors applied; 19.35% in structural domain
T.E.S.T. v4.1		305.83	2.49	Consensus method; in domain
EPISuite v4.11	Regression-based estimate	2160	3.33	The substance is within the applicability domain.
	Arnot-Gobas upper trophic level; incl. biotransformation estimates	138.1	2.140	The substance is within the applicability domain.
	Arnot-Gobas upper trophic level; incl. biotransformation rate of zero	1454	3.163	The substance is within the applicability domain.
VEGA CAESAR v2.1.13		21	1.33	According to the model’s global AD index, the predicted substance is out of the Applicability Domain of the model.
VEGA Meylan v1.0.2		2160	3.33	According to the model’s global AD index, the predicted substance is out of the Applicability Domain of the model.
VEGA Read across v1.0.2		188	2.27	According to the model’s AD index, the read-across seems to be unreliable due to low similarity in found molecules.

 

Although the interpretation of the QSAR estimations is difficult it is not expected that the compound significantly accumulates in organisms. 

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 compound was inside the parametric and the mechanistic domains of the compound but only 19.35% of the fragments of the target chemical are present in correctly predicted training chemicals. Although this makes the prediction not very reliable the model delivers further useful information on the compounds bioaccumulative behavior, i.e. the DiamMax-average and the molecular length of the compound. Regarding the BCF value the model estimated a BCF of 7.08 with all mitigating factors applied. Metabolism and the size of the compound have the biggest influence on the bioaccumulative potential.

 

US EPA’s Toxicity Estimation Software Tool (T.E.S.T.) uses five submodels to estimate the BCF of the target chemical. These results are then averaged in the consensus approach to provide a higher reliability. With the exception of the Group Contribution Method, the target compound is inside of the applicability domain of the single submodels . However the confidence in the estimated BCF values of the single submodels is not optimal. The consensus model predicts the BCF by calculating the average of the predicted BCF values from the other QSAR methodologies while taking the applicability domain of the models into account. This method typically provides the highest prediction accuracy since errant predictions are dampened by the predictions from the other methods. In addition this method provides the highest prediction coverage because several methods with slightly different applicability domains are used to make a prediction. The averaged result of the consensus method was a BCF of 305.83.

 

US EPA’s EPISuite includes the regression-based estimation and the Arnot-Gobas model which takes biotransformation processes into account. The present chemical is within the molecular weight and the logKow ranges of both the regression-based estimation and the Arnot-Gobas model. The regression-based model did not take any correction factors into account and the prediction resulted in a BCF of 2160. For the determination of the biotransformation rate constant the model detected one fragment that exceeded the maximum number of instances of the training set. However, the result seems to be reliable and delivers useful information on the metabolic behavior of the compound. Without considering the biotransformation rate the Arnot-Gobas model predicted a BCF of 1454. However, taking the biotransformation rate into account which represents more realistic conditions the BCF is predicted with 138.1 for the upper trophic level. It has to be kept in mind that the model uses fish with higher lipid contents as 5% recommended in the OECD test guideline to build the single model. Taking the lipid content into account the BCF would be even lower. 

 

The VEGA package includes three different estimation tools with each of them providing detailed information on the applicability domain. Neither of the models delivered a reliable result. The domain score of the models delivered a bad assessment and consequently the models were not taken into account.

 

Although the results of the QSAR models are difficult to interpret the compound is not regarded to have a high potential to bioaccumulate. Above all the information on the mitigating effect of metabolism which was deduced by both Catalogic and the US EPA’s Arnot-Gobas model is a clear indicator that the compound does not significantly accumulate. This assumption is further supported by the compound’s dimension. 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 compound has a molecular weight of only 430 the DiamMax-average is 2.3 nm and even the DiamMax-Min is 2.2 nm. Therefore it can be assumed that the compound does not easily cross biological membranes.

 

In conclusion, the compound is not regarded to have a significant potential to accumulate in organisms.