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

Endpoint summary

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

There were no studies available in which the toxicokinetic properties of the test substance were investigated. 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 this assessments are given below.

Chemistry

The test substance (CAS 204583-39-1) (molecular weight of 609 Da) is a slightly yellow powder whose water solubility (deionised water) is < 0.74 mg/L and its fat solubility is 14.7 g/L (CIBA Specialty Chemicals, 2002).The calculated log Pow is 10.3.

Absorption

In an acute oral and dermal toxicity study, respectively, rats were administered to the test substance. No mortalities or clinical signs of toxicity were observed in doses of 2000 mg/kg bw, indicating primarily a low level of oral and dermal toxicity (RCC Ltd, 2002, see chapter 7.2.1 acute oral toxicity and 7.2.2 acute dermal toxicity). The NOAEL in male and female rats in a subacute oral repeated dose study is 1000 mg/kg bw (RCC Ltd, 2002, see chapter 7.6.1).The rigid triazine core determines the bulky shape of the molecule. In regard of the poor water solubility and the absence of hydrolysable groups, the test substance cannot undergo pH-dependent hydrolysis in the stomach. As it does not bear resemblance to fatty acids, uptake via micelles with bile acids is unlikely. The calculated dimensions for the equilibrium conformation of the test substance are in the range of 19 to 22 Å (CIBA Inc., 2009). For hydrophobic substances, a diameter of 9.5 Å was identified as a threshold for loss of membrane permeation (Opperhulzen, et al., 1985). Therefore, the large diameter supports the assessment of a low level of uptake, even though a molecular weight of more than 1100 Da is given as an additional criterion for limited bioaccumulation potential (Brooke and Cronin, 2009). Bulky substances may be taken up via Peyer’s Patches in the small intestine. However, this generally leads to their destruction in the macrophages. Skin penetration can be excluded based on model calculation (Fitzpatrick, et al., 2004). The test substance has a comparably very low vapour pressure. It was estimated to be 5.4E-22 Pa at 25 °C based on the boiling point calculated and using the Modified Watson Correlation (RCC Ltd, 2002); subsequently, the calculated vapour saturation threshold at 25°C is ca. 1.35E-22 mg/L. This indicates that absorption of the substance via vapour inhalation is not relevant.

Metabolism

Oral administration of the test substance to Wistar rats at doses of 50, 200 and 1000 mg/kg/day, for 28 days resulted in no test item-related effects upon mortality and no differences in food consumption or body weight development (RCC Ltd, 2002). The hematology, clinical biochemistry and urinalysis parameters did not show test item-related differences when compared with those of the controls. Organ weights of test item-treated animals were unaffected, and macroscopical/microscopical findings were of no toxicological relevance. There was a transient minor reduction of locomotor activity in both sexes treated with 1000 mg/kg/day. This finding was not considered to be adverse and does not indicate systemic availability. Based on the results of this study, 1000 mg/kg/day was considered to be the no observed- adverse-effect-level (NOAEL). No indication of uptake or chemical reactivity was observed in any study, including acute studies, irritation, sensitization and genotoxicity in vitro as well as the above described subacute study. In the unlikely case of uptake, potential metabolism might involve oxidative O-dealkylation and phase-II conjugation (glucuronidation or sulfonation) of aromatic alcohols. The test substance is not expected to accumulate in the body.

Excretion 

Due to a likely metabolism throughoxidative O-dealkylation and phase-II conjugation of aromatic OH-groups it isexpected that the test substance might be excreted predominantly via the urine.The alkyl chain would be degraded via β-oxidation. Overall, the test substance is not expected to accumulate in the body.

Used references:

Brooke, D. and Cronin M. (2009). Calculation of Molecular Dimensions Related to Indicators for Low Bioaccumulation Potential.,Environment Agency

Ciba Inc., 2009: Equilibrium conformation calculated with AM1/MMFF94 (Merck Molecular Force Field, within Spartan ’04, Wavefunction Inc.) by Hugo Camenzind, Innovation Process Support, CH-4002 Switzerland, performed August 3, 2009, project no. Teubner_W_040809

Fitzpatrick, D., et al. (2004). "Modelling skin permeability in risk assessment-the future." Chemosphere 55 (10): 1309-14.

Opperhulzen, A., et al. (1985). "Relationship between bioconcentration in fish and steric factors of hydrophobic chemicals." Chemosphere 17: 1871- 1896.

RCC Ltd, (2002):Calculation of the vapour pressure of CGX UVA-006 (TKA 40256). RCC Ltd. Report no.: 842513,Owner company: BASF SE, Report date:20.03.2002