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EC number: 606-251-8 | CAS number: 1917-44-8
Endpoint summary
Administrative data
Link to relevant study record(s)
Description of key information
Key value for chemical safety assessment
Additional information
Assessment of the toxicokinetik behaviour of test substance (CAS 1917-44-8):
There were no studies available in which the toxicokinetic properties of the test substance were investigated.
The test substance (molecular weight of 249.21 g/mol) consists of white crystals (Ciba-Geigy, 1993) with a log Pow of 1.8 (RCC, 2003a) a water solubility of 0.8 mg/L (RCC, 2003b).
Absorption
In an acute toxicity study in rats no mortality were observed after oral administration of test substance (Ciba-Geigy Ltd., 1993). Various clinical signs as hunched posture, piloerection and dyspnea were observed. These symptoms were not very specific and could not be seen as substance-related without doubts. Thus, no conclusion can be drawed regarding systemic distribution of the test substance. Generally the smaller the molecule the more easily it may be taken up. Molecular weights below 500 g/mol are favourable for absorption; molecular weights above 1000 do not favour absorption (ECHA GD 7c, 2008). Based on molecular weight the test substance could be absorbed in the gastrointestinal tract. Another important factor is the water solubility, which is low for the test substance.Water-soluble substances will readily dissolve into the gastrointestinal fluids. Absorption of very hydrophilic substances by passive diffusion may be limited by the rate at which the substance partitions out of the gastrointestinal fluid. Passage through aqueous pores is not very likely to happen, due to the molecular weight which should be <200 g/mol (ECHA GD 7c, 2008).
Furthermore, passive diffusion is possible because of the moderate log P (1.8). The compound may not be taken up by micellular solubilisation, a mechanism which is of particular importance for highly lipophilic compounds (log P >4), particularly those that are poorly soluble in water (1 mg/l or less) (ECHA GD 7c, 2008).
No information from acute or repeated dose toxicity or sensitization studies are available, which could provide information about the systemic distribution of the test substance after dermal exposure. Highly lipophilic substances (log P 4-6) that come into contact with the skin can readily penetrate the lipid rich stratum corneum but are not well absorbed systemically. Although they may persist in the stratum corneum, they will eventually be cleared as the stratum corneum is sloughed off. For a log P of 1-4 dermal absorption is favored, especially when the substance is soluble in water. Furthermore, chemicals with a molecular weight <100, dermal uptake is favored, while chemicals with a molecular weight >500, dermal uptake is not favored (ECHA GD 7c, 2008). In conclusion, a dermal absorption of the test substance seems not very likely, based on the log P and the water solubility which is proposed to result in a low dermal uptake.
No information from acute or repeated dose toxicity studies are available, which could provide information about the systemic distribution of the test substance after inhalation. The test substance itself has a very low vapor pressure of <0.01 Pa at 25°C (RCC, 2003c). Therefore, a low potential of toxicity of the substance vapor via the inhalative route is considered. No information on particle size distribution is availabale. Thus, the absorption of dust via the inhalative route can not be assessed.
Metabolism
Using the OECD toolbox vs. 2.0, the liver metabolism simulator provided 32 potential metabolites, and the skin simulator 2 potential metabolites (OECD toolbox vs.2.0, 2010). In general, the liver simulator predicted hydroxylation of the aromatic rings and of the heterocyclic ring, leading to an opening of the triazine moiety. Additionally some epoxides were predicted for the aromatic ring system. A study on genotoxicity (Ames-Test) gave no indication of a reactivity of the substance or its metabolites under the test conditions. Furthermore, the skin simulator predicted 2 metabolites where the aromatic ring was hydroxylated (OECD toolbox vs.2.0, 2010).
Excretion
The parent compound and the potential metabolites have a molecular weight a lower than 300 g/mol and were considered as soluble in water. Thus, they are expected to be excreted predominantly via the urine (ECHA GD 7c, 2008).
References
RCC Ltd. (2003a) Determination of the partition coefficient (N-octanol/water) of TKA 40280, Study number 845917
RCC Ltd. (2003b) Determination of the water solubility of TKA 40280, Study number 845916
RCC Ltd. (2003c) Calculation of the vapour pressure of TKA 40280, Study number 845914
European Chemicals Agency (2008) Guidance on information requirements and chemical safety assessment. Chapter R.7c: Endpoint specific guidance
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