2-(4,6-bis(2,4-dimethylphenyl)-1,3,5-triazin-2-yl)-5-(3-((2-ethylhexyl)oxy)-2-hydroxypropoxy)phenol

Bioaccumulation: aquatic / sediment

Description of key information

The test substance does not significantly accumulate in organisms.

Additional information

The bioaccumulation potential of the test substance was tested in a guideline study according to OECD 305C with Japanese carp (Institute of Ecotoxicology, Gakushuin University 1997). A BCF below 11 was measured after 8 weeks of exposure and the test substance does not significantly accumulate in fish. Despite the use of an emulsifier the test is regarded suitable in a weight of evidence since the low exposure level (0.05 mg/L) is below the determined water solubility (< 0.1 mg/L) and within the range of solubility that was determined in the test media in the aquatic toxicity tests on algae, daphnia and fish (mean measured: 0.029 - 0.062 mg/L). Thus the BCF value of < 11 is regarded as reliable.

However, the results are supported by the calculated logPow of 9.6, the molecular weight (583.771 g/mol) and the maximum diameter of the molecule that was calculated using CATALOGIC v 5.13.1.156. It resulted in an average maximum diameter (Dmax_aver) of 2.2 nm. According to the guidance on information requirements and chemical safety assessment Chapter R.11 - PBT Assessment - another parameter that directly reflect the molecular size of a substance is the average maximum diameter (Dmax_aver). 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 Dmax_averlarger than 1.7 nm the BCF value was less than 5000 L/kg. It can be assumed combining 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. Furthermore, the aquatic BCF of a substance is probably lower than 2000 L/kg if the calculated log Kow is higher than 10.

Additionally, four different calculations were conducted to support these results.

Model		BCF	Log BCF	Remarks
Catalogic v5.13.1.156		8.91	0.95	all mitigating factors applied; 80.95 % in domain
T.E.S.T. v4.01		43.74	1.64
EPISuite v4.11	Regression-based estimate	120	2.08	The substance is within the applicability domain of the BCFBAF submodel: Bioconcentration factor
	Arnot-Gobas upper trophic level	2.548	0.406	Including biotransformation rate estimates; MW is within the range of training set. Log Kow outside of range of training set. Therefore, the estimate may be less accurate.
	Arnot-Gobas mid trophic level	3.207	0.506	Including biotransformation rate estimates;MW is within the range of training set. Log Kow outside of range of training set. Therefore, the estimate may be less accurate.
	Arnot-Gobas lower trophic level	3.449	0.538	Including biotransformation rate estimates;MW is within the range of training set. Log Kow outside of range of training set. Therefore, the estimate may be less accurate.
VEGA CAESAR v2.1.14		2	0.27	The test substance is outside the Applicability Domain of the model

Regarding the results of the model calculation, the calculated BCF values range from 2 (VEGA) to 120 (Regression-based estimate).

Of these models, Catalogic, VEGA CAESAR and the Arnot-Gobas model from EPISuite v4.10 take into account mitigating factors, e.g. metabolism, water solubility and/or size.

Catalogic revealed a corrected BCF of 8.91 and the compound is 80.95% 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 2.548 (upper trophic level) to 3.449 (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, only the MW is within the range of training set.  

The Log Kow is outside of the range of training set. Therefore, the estimate may be less accurate. Nevertheless, since it is a worst-case consideration, the values can be used in the weight of evidence.

The regression-based estimate from the EPISuite revealed a BCF value of 120 based on a calculated logKow of 9.6 and the test substance is in the applicability domain of the model. However, for the regression based estimate mitigating factors are not taken into account and, therefore, this value is an absolute worst-case and more realistic BCF values according to the Arnot-Gobas model are definately lower.

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 43.74.

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 2. 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 where the applicability domain is met are consistent with the results of all models.

In overall conclusion, regarding all available information the test item does not significantly accumulate in organisms.

QSAR-disclaimer

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 not entirely fulfilled, but deemed sufficiently covered for a weight-of-evidence approach.Therefore, and for reasons of animal welfare, further experimental studies on aquatic bioaccumulation are not provided.