2,4-di-tert-butylphenyl 3,5-di-tert-butyl-4-hydroxybenzoate

Bioaccumulation: aquatic / sediment

Description of key information

Significant accumulation in organisms is not to be expected. 

Additional information

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 CAS 4221-80-1 (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.

 

The bioaccumulative potential of EC 213-590-1 was assessed in a weight of evidence approach including several QSAR estimations and data on the molecular size and log Kow.The single QSAR models and their results are summarized in the table below.

Model		BCF	logBCF	Remarks
Catalogic v5.11.15		12.02 (corrected)	1.08	all mitigating factors applied; only 53.13% in domain
		297.65 (max)	2.4737	No mitigating factors applied; only 53.13% in domain
T.E.S.T. v4.1		2992.61	3.48	Consensus method; in domain; low reliability
EPISuite v4.11	Regression-based estimate	270	2.43	Within the applicability domain
	Arnot-Gobas upper trophic level; incl. biotransformation estimates	5.621	0.750	The substance is within the molecular weight range but outside the logKow range.
	Arnot-Gobas upper trophic level; incl. biotransformation rate of zero	84.13	1.925	The substance is within the molecular weight range but outside the logKow range.
VEGA CAESAR v2.1.13		22	1.34	According to the model’s global AD index, the predicted substance could be out of the Applicability Domain of the model.
VEGA Meylan v1.0.2		215	2.33	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		71	1.85	According to the model’s global AD index, the predicted substance is out of the applicability domain of the model.

 

According to the results of the models the compound does not have a bioaccumulative potential. 

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 53.13% of the fragments of the target chemical are present in correctly predicted training chemicals. Nevertheless, the result is regarded as reliable and suitable to be used in a weight of evidence approach. With all mitigating factors applied the BCF is determined as 12.02. The biggest influence on the bioaccumulative potential has the metabolism and the size both limiting the uptake. Furthermore, even without considering any mitigating factors the BCFmax is only at 297.65 L/kg.

 

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 than averaged in the consensus approach to provide a higher reliability. 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 low and the results are therefore questionable. 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 2992.61. Due to the low reliability of every single submodel the result of T.E.S.T was not taken into account in the weight-of-evidence approach.

 

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 applicability domain of the regression-based estimation and molecular weight range but outside the log Kow range of both the regression-based estimation and within the molecular weight range but outside the logKow range of the Arnot-Gobas model. The regression-based model predicted a BCF of 270 L/kg. Corrections for an tert-butyl ortho-phenol group were applied in the equation used for the estimation. The Arnot-Gobas model predicted BCF values of 5.621 and 84.83 L/kg for the upper trophic level including biotransformation rate estimates and biotransformation rates of zero. The EPISuite results were regarded as suitable in the weight of evidence approach.

 

The VEGA package includes three different estimations tools with each of them providing detailed information on the applicability domain. Each model was taken into account in the weight-of-evidence approach although the compound was out of the applicability domain of the Meylan and the Read-across model. Nevertheless, the different compounds detected by the single models for the assessment comprise key structures (two planar rings, polar groups, aliphatic side chains) which are relevant for bioaccumulation and which are also present in the target chemical. None of these compounds has experimentally significant BCF values and it was concluded that the target chemical is therefore not bioaccumulative. Moreover, several structural alerts usually present in non-bioaccumulative compounds have been detected which are also a sign that the target chemical has a low bioaccumulative potential. The BCF values of the CEASAR, Meylan and Read-across models were 22, 215, and 71, respectively.

 

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. The present compound has a DiamMax-average of 1.6709. Although the molecular weight is only 438.6 it can be concluded that the compound has a limited potential to cross biological membranes. Furthermore, the aquatic BCF of a substance is probably lower than 2000 if the calculated logKow is higher than 10. The present compound has a calculated logKow of 10.00.

 

In conclusion, with the exception of the data from T.E.S.T. which were excluded from the assessment all available estimations are extremely well in line and the BCF of the target compound is expected to be below 500.

Furthermore, the BCF values which were derived by models considering mitigating factors as size and metabolisme were < 100.