Phenol, 2-[4,6-bis([1,1'-biphenyl]-4-yl)-1,3,5-triazin-2-yl]-5-[(2-ethylhexyl)oxy]-

Bioaccumulation: aquatic / sediment

Description of key information

The test substance does not 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 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.

In a bioaccumulation study according to OECD 305, Carp (Cyprinus carpio) were exposed to two concentrations of the test substance for a period of 4 weeks. The determined bioconcentration factor was <9. Despite the use of an emulsifier the test is regarded as valid since the high (0.2 mg/L) and the low exposure level (0.02 mg/L) are below the determined water solubility (< 0.73 mg/L).

However, the results are supported by the calculated logPow of 10.7 and the molecular weight (605.78 g/mol) of the test item. 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 v5.11.1. It resulted in a maximum diameter of 2.17 to 2.6 nm. The Dmax Average was calculated to be 2.35 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.

Additionally, to support these findings four QSAR calculations have been conducted. The single models and their results are summarized in the table below:

Model		BCF	LogBCF	Remarks
Catalogic v5.11.19		7.41	0.87	all mitigating factors applied; 75 % in domain
T.E.S.T. v4.01		26.28	1.42
EPISuite v4.11	Regression-based estimate	63.8	1.8	The substance is within the applicability domain of the BCFBAF submodel: Bioconcentration factor
	Arnot-Gobas upper trophic level	6.93	0.841	Including biotransformation rate estimates; MW is within the range of training set, but exceeds 600 g/mol. And Log Kow is outside of the range. Therefore, the estimate may be less accurate
	Arnot-Gobas mid trophic level	9.52	0.979	Including biotransformation rate estimates; MW is within the range of training set, but exceeds 600 g/mol. And Log Kow is outside of the range. Therefore, the estimate may be less accurate
	Arnot-Gobas lower trophic level	10.51	1.021	Including biotransformation rate estimates; MW is within the range of training set, but exceeds 600 g/mol. And Log Kow is outside of the range. Therefore, the estimate may be less accurate
VEGA CAESAR v 2.1.14		7	0.87	The test substance is out of model Applicability Domain

 

 Regarding the results of the model calculation, the calculated BCF values range from 6.93 (Arnot-Gobas upper trophic level) to 63.8 (EPISuite v4.11).

Of these models, Catalogic, VEGA CAESAR and the Arnot-Gobas model from EPISuite v4.11 take into account mitigating factors, e.g. metabolism, water solubility and/or size.

Catalogic revealed a corrected BCF of 7.41 and the compound is 75% within the model’s applicability domain.

The Arnot-Gobas model from the EPISuite takes into account the biotransformation rate of the compound and calculates BCF values for the upper, mid and lower trophic levels. The values for the present compound range from 6.93 (upper trophic level) to 10.51 (lower trophic level). The model assumes default lipid contents of 10.7%, 6.85% and 5.98% for the upper, middle and lower trophic levels, respectively. Usually, in the context of REACH a default lipid value of 5% is assumed which represents the average lipid content of the small fish used in OECD 305 studies. Thus, the higher lipid values of the Arnot-Gobas model can be regarded as reasonable worst-case scenarios as higher lipid contents are usually associated with a higher potential for bioaccumulation. However, the MW is within the range of training set, but exceeds 600 g/mol. And Log Kow is outside of the range. Therefore, the estimate may be less accurate.

The regression-based estimate from the EPISuite revealed a BCF value of 63.8 based on a calculated logKow of 10.68 and the test substance is in the applicability domain of the model.

The T.E.S.T. package from the US EPA estimates BCF values using several different advanced QSAR methodologies. The recommended model of the T.E.S.T. package is the consensus method since it provides the most accurate prediction. This model estimates the BCF by taking an average of the predicted BCF values from the other applicable QSAR methods of the package. For the present substance the consensus method averaged the results from (1) the hierarchical clustering method, (2) the single model method, (3) the group contribution method, (4) the FDA method and (5) the nearest neighbor method. The resulting BCF value is 26.28.

The VEGA model was developed with several descriptors and is based on a dataset of 473 compounds. It offers detailed information on the applicability domain. In the present case, the calculation gave a BCF value of 7. Since the Global AD Index was calculated to be 0 the substance is out of the Applicability Domain of the model.

However, even though the test substance was out of the Applicability Domain of some programs, the QSAR results support the overall conclusion that the test substance is not bioaccumulative, since all QSAR models give a value far below a BCF of 2000 and the results of the models were the applicability domain is met are consistent with the results of all models.

Furthermore, regarding the toxicokinetics, there were no studies available in which the toxicokinetic properties of the test substance were investigated. However, based on the large molecular size, the absence of adverse findings in toxicity studies, and the presence of functional groups for metabolism, a potential for bioaccumulation is unlikely. Further details for the toxicokinetc assessment are given in the chapter 7.1.

In overall conclusion, considering the test results, the logPow > 10, the high molecular weight, the high average maximum diameter, the QSAR calculations and the toxicokinetics conclusion it can clearly be stated that test substance is not bioaccumulative according to PBT-criteria.