2-(4,6-diphenyl-1,3,5-triazin-2-yl)-5-((hexyl)oxy)phenol

Bioaccumulation: aquatic / sediment

Description of key information

Does not significantly accumulate in organisms.

Additional information

The bioaccumulation potential of the substance was tested in a guideline study following OECD 305 (Institute of Ecotoxicology, Gakushuin University 1994b). Japanese carp (Cyprinus carpio) were exposed to the substance for 8 weeks. The determined bioconcentration factor was <8.1 and thus it was concluded the test item does not significantly accumulate in fish. However, both test concentrations were tested above the measured water solubility using an emulsifier. Therefore, the determined BCF value is less reliable. To strengthen the assessment an extensive weight of evidence approach has been conduted to draw a conclusion about the bioaaccumulation potential:

Regarding the bioaccumulation potential, the maximum diameter of the molecule is taken into consideration, as the diameter of the molecule may hinder the uptake of the substance (as reported in R.11 - PBT Assessment). From a diverse set of molecules it has been determined that substances with a Dmax[aver] larger than 1.7 nm, have BCF values of less than 5000 L/kg. The average maximum diameter of 2-(4,6-diphenyl-1,3,5-triazin-2-yl)-5-((hexyl)oxy)phenol (Dmax[aver]) was calculated with CATALOGIC software and determined to be 1.96 nm. Based on the calculated Dmax[aver], it can be assumed that the test item will not easily pass cell membranes, that update 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	Log BCF	Remarks
Catalogic v5.11.19		66.07	1.82	all mitigating factors applied; 66.67 % in domain
T.E.S.T. v4.01		95.42	1.98
EPISuite v4.10	Regression-based estimate	1850	3.27	The substance is within the applicability domain of the BCFBAF submodel: Bioconcentration factor
	Arnot-Gobas upper trophic level	117.8	2.071	Including biotransformation rate estimates; MW and logKow is within the range of training set.
	Arnot-Gobas mid trophic level	119.3	2.077	Including biotransformation rate estimates;MW iand logKow is within the range of training set.
	Arnot-Gobas lower trophic level	161.5	2.208	Including biotransformation rate estimates;MW and logKow is within the range of training set.
VEGA CAESAR v2.1.13		11	1.05	The test substance is out of model Applicability Domain

 

Regarding the results of the model calculation, the calculated BCF values range from 11 (VEGA) to 1850 (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 66.07 and the compound is 66.67% 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 117.8 (upper trophic level) to 161.5 (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. The MW and logKow is within the range of training set.

The regression-based estimate from the EPISuite revealed a BCF value of 1850 based on a calculated logKow of 6.24 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 and below 200.

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 95.42.

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 11. Since the Global AD Index was calculated to be 0.462 the substance isout 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.

 

Finally, bioaccumulation of the test substance is considered unlikely, due to the fact that the test item is most likely not absorbed from the gastrointestinal system (mammalian toxicity data). Based on the low water solubility and large molecular weight of the test substance, only a small amount of the article is expected to adsorb. The majority of ingested test item is expected to pass the intestines unchanged and to be excreted directly. Toxicokinetic studies on an analogue showed that the compound is not detectable in the blood and demonstrated a very low level of distribution after single oral administration. 96h after dosing, less than 0.01% of the analogue was found in the tissue.

 

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 of2-(4,6-diphenyl-1,3,5-triazin-2-yl)-5-((hexyl)oxy)phenol (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.