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EC number: 247-952-5 | CAS number: 26741-53-7
Bioaccumulation: aquatic / sediment
Administrative data
Link to relevant study record(s)
Description of key information
A significant accumulation in organisms is not expected.
Key value for chemical safety assessment
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 the test substance (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 aquatic bioaccumulation are not provided.
Experimental data on the bioaccumulation behavior of the test substance are not available. However, the bioaccumulation potential of the test item is evaluated in a weight of evidence:
A low potential of bioaccumulation can be assumed since the calculated logKow of the test item is 10.9 and the molecular weight is above 500 g/mol (604.694 g/mol). According to the guidance on information requirements and chemical safety assessment Chapter R.11 - PBT Assessment - the aquatic BCF of a substance is probably lower than 2000 L/kg if the calculated log Kow is higher than 10. Furthermore, the maximum diameter of the molecule was calculated using CATALOGIC v5.11.19. It resulted in an average maximum diameter of 2.02 nm. According to the guidance on information requirements and chemical safety assessment Chapter R.11 another parameter that directly reflects the molecular size of a substance is the average maximum diameter (Dmaxaver). Very bulky molecules will less easily pass the cell membranes. This results in a reduced BCF of the substance. From a diverse set of chemicals it appeared that for compounds with a Dmaxaver larger than 1.7 nm the BCF value was less than 5000 L/kg. It can be assumed combining the high logKow, the maximum diameter of above 1.7 nm and the high molecular size of the test item that the test item will not easily pass the cell membranes, the uptake is reduced and bioaccumulation will not occur.
These findings are supported using four scientifically acceptable calculation models:
(1) Catalogic v5.11.19, BCF base-line model v02.09
(2) US EPA EPISuite v4.11, BCFBAF v3.01
(3) US EPA T.E.S.T. v4.2.1
(4) Vega v1.1.3 including CAESAR v2.1.14, Meylan v1.0.3 and Read-across/KNN v1.1.0
In regards to the reliability of the QSAR predictions the results from the models included in the Vega model were not taken into account for the general prediction because the substance was not within the applicability domain of all Vega models.
The domain of the BCF base-line model implemented in Catalogic is divided in three sub-domains. (1) The parameter domain which compares the logKow, water solubility and molecular size of the substance to the specific ranges of the training set, (2) the structural fragment domain which compares the atom-centered fragments of the substance to the ones from the training set and (3) the mechanistic domain which evaluates the general uptake mechanism of the compound as only such chemicals which are taken up by passive diffusion can be predicted. The current substance was within the parameter and the mechanistic domain of the model. In regards to the structural domain, 48.39 % of the fragments of the substance could be found in correctly predicted training chemicals. 25.81% of the fragments were not present in the training chemicals and 25.81% of the fragments were found in non-correctly predicted training chemicals. Principally, the substance is not completely within the domain of the model as not all atom-centered fragments could be found in correctly predicted training chemicals, however, the result is regarded as reliable and adequate for the use in a weight of evidence approach and support the overall conclusion. The predicted BCF value was determined to be 7.76 L/kg. Metabolism, size and to a minor extent water solubility were the most important mitigating factors decreasing the BCF value.
The US EPA’s EPISuite includes a regression-based BCF prediction and a prediction taking the biotransformation rate into account. Concerning the regression based prediction the compound was within the molecular weight and logKow ranges of the model. Furthermore, the maximum number of fragments was not exceeded. Therefore, the result of the regression-based estimation is reliable and is regarded as adequate in the weight of evidence approach. The model predicted the BCF with 164 L/kg.The second model takes the biotransformation of the compound into account. However, the test substance was not completely within the applicability domain of the model. The molecular weight was within the range of the training set, but exceeded 600 g/mol. Furthermore, the logKow was outside the range of the training set. Therefore, the estimate may be less accurate. A BCF of 10.36 L/kg (upper trophic level) was estimated. Even though the result may be less accurate, it supports the overall conclusion in this weight of evidence approach and is regarded as acceptable.
US EPA’s T.E.S.T. model combines 5 methods in the consensus approach. The model only delivers results if the substance is in the applicability domain of the respective model. No results were calculated for the hierarchical clustering, the single model and the group contribution. The FDA method determined a BCF of 170.74 and the nearest neighbor method resulted in a BCF of 29.98. Therefore, the consensus method gave a BCF of 71.55. However, the confidence of the results is low due to the mean absolute error of the single results. Nevertheless, the results are regarded as reliable in a weight of evidence approach since the similarity coefficient is close to the limit values.
In conclusion, in the weight of evidence approach using all available data, it can be concluded that the test substance does not significantly accumulate in organisms.
Since it can be expected that the test substance undergoes a very slow process of hydrolysis and formation of hydrolysis products cannot be excluded, the bioaccumulation potential of the hydrolysis products is also considered:
The hydrolysis products would be 2,4-di-tert-butylphenol, pentaerythritol and phosphorous acid that will be oxidized to phosphoric acid.
2,4-di-tert-butylphenol was already evaluated by the PBT Working Group in 2008 (ECB Summary Fact Sheet; PBT List No. 12). The PBT working group concluded that 2,4-di-tert-butylphenol has a moderate bioaccumulation potential with a BCF of 128 – 436 and does not meet the B criterion.
Additionally, 2,4-di-tert-butylphenol was evaluated in 2015 (PACT). It was also concluded, that 2,4-di-tert-butylphenol does not fulfil the B criterion. Both experimental and predicted BCF-values are well below the cut-off value for bioaccumulation for aquatic organisms as given in Annex XIII of REACH. This conclusion applies for the parent compound and it is reasonable to expect that also the transformation products do not meet the definitive B-criteria.
Therefore, 2,4-di-tert-butylphenol does not significantly accumulate in organisms.
Pentaerythritol was evaluated in an OECD SIDS dossier in 1998 (SIDS Initial Assessment Report for 8th SIAM). It was concluded that the bioaccumulation potential is very low (BCF 0.3 – 2.1; logKow < 0.3). Therefore, pentaerythritol does not meet the B-criteria and does not significantly accumulate in organisms.
Concerning phosphoric acid an OECD SIDS dossier exists also (SIDS Initial Assessment Report for SIAM 28, 2009). The bioaccumulation potential seems to be low based on a BCF value of 3.162 estimated with BCFWIN (from the US EPA EPI Suite). Furthermore, bioaccumulation is not anticipated for inorganic compounds that are miscible with water such as phosphoric acid.
Hence, in overall conclusion, the potential hydrolysis products do not significantly accumulate in organisms and the B criterion is not met.
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