Diethyl [[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methyl]phosphonate

Bioaccumulation: aquatic / sediment

Description of key information

The compound is not expected to significantly accumulate in organisms. 

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 ofCAS 976-56-7 (Q)SAR results were used for 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 the compound was assessed in weight-of-evidence approach using data from the analogue substance CAS 65140-91-2 together with several QSAR calculations. A detailed read-across justification is attached to the endpoint study record.

 

The read-across substance was conducted at the Gakushuin University, Japan. Two concentrations were tested (3 mg/L and 0.3 mg/L). The BCF values were ≤ 20.6 in the higher concentration group and ≤ 52.3 in the lower concentration group. The study was conducted with the common carp in accordance with OECD guideline 305.

 

This result is supported by the QSAR estimations which are summarized in the table below.

 

Model		BCF	LogBCF	Remarks
Catalogic v5.11.16		295.1	2.47	all mitigating factors applied; 70.83% in structural domain
T.E.S.T. v4.1		171.1	2.23	Consensus method; in domain
EPISuite v4.11	Regression-based estimate	130.7	2.12	The substance is within the molecular weight and logKow ranges of the training set compounds. The maximum number of instances of one fragment was exceeded.
	Arnot-Gobas upper trophic level; incl. biotransformation estimates	121.1	2.083	The substance is within the applicability domain.
	Arnot-Gobas upper trophic level; incl. biotransformation rate of zero	1151	3.061	The substance is within the applicability domain.
VEGA CAESAR v2.1.14		32	1.51	According to the model’s global AD index, the predicted substance is out of the Applicability Domain of the model.
VEGA Meylan v1.0.3		1088	3.04	According to the model’s global AD index, the predicted substance is out of the Applicability Domain of the model.
VEGA Read across v1.1.0		371.5	2.57	According to the model’s AD index, the read-across seems to be unreliable due to low similarity in found molecules. The predicted substance is out of the Applicability Domain of the model.

 

According to the QSAR results the compound is not expected to significantly accumulate in organisms. The BCF is expected to be below 500.

 

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 and 70.83% of the fragments of the target chemical are present in correctly predicted training chemicals. The mitigating factors metabolism and size have the biggest influence on the bioaccumulative potential of the compound. The model determined a BCF of 295.1 with all mitigating factors applied. The result is regarded to be reliable and suitable in a weight-of-evidence approach.

 

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. The target compound is inside of the applicability domain of all 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 171.1. The result is regarded to be reliable and suitable in a 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 molecular weight and the logKow ranges of both the regression-based estimation and the Arnot-Gobas model. The regression-based model applied a correction factor for a tert-butyl ortho-phenol group. This group is present twice in the compound and thus the maximum number of fragments is exceeded. However, this is not regarded to have a significant effect on the outcome of the prediction as the additional tert-butyl group is expected to have a decreasing effect on the bioaccumulative potential due to sterical hindrance and limited uptake. The regression-based estimation methodology resulted in a BCF of 130.7. For the determination of the biotransformation rate constant and the BCF/BAF with the Arnot-Gobas method the compound was inside the applicability domain and the resulting BCF was 1151 for the upper trophic level with a biotransformation rate of zero. However taking the biotransformation rate into account which represents more realistic conditions the BCF was determined to be 121.1. 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. Therefore, the result can be regarded as worst case estimation.

 

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.

 

In conclusion, the bioaccumulative potential of the substance was assessed in a weight-of-evidence approach with data from an analogue substance (CAS 65140-91-2) and several QSAR estimations. The experimental data from the analogue compound is clearly supported by the valid QSAR results. The BCF of CAS 976-56-7 is expected to be clearly below 500 and accumulation in organisms is not expected.