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Description of key information

Key value for chemical safety assessment

Additional information

Assessment of the toxicokinetic behavior of test substance:

There were no studies available in which the toxicokinetic properties of the test substance were investigated. The test substance (molecular weight of 331.5 g/mol) is a white to reddish-yellow solid powder (Ciba-Geigy, 1974) with a log Pow of 8.2 (EPI Suite, 2012) and a water solubility of 1.7 µg/L (BASF, 2012). The vapor pressure was determined at 0.0000014 Pa at 20°C (Ciba-Geigy, 1986).

Absorption

In an acute toxicity study in rats no mortality and no systemic findings were observed after oral administration of test substance (Ciba-Geigy Ltd., 1974). Therefore no conclusion can be drawn regarding systemic distribution. Generally the smaller the molecule, the more easily it may be taken up. Molecular weights below 500 g/mol are favorable for absorption; molecular weights above 1000 g/mol do not favor absorption (ECHA GD 7c, 2008). Based on molecular weight the test substance could be absorbed in the gastrointestinal tract. However, the water solubility of the test article is very low, thus not favoring the substance to be readily dissolved in gastrointestinal fluids. Furthermore, passive diffusion is also not very likely to happen because of the high log P (> 4) of the test substance. To summarize, based on the physico-chemical parameters, the potential for absorption through the gastrointestinal tract is considered to be low but cannot be entirely be ruled out. In a subacute repeated dose toxicity study (WIL, 2012), no toxicological relevant effects were reported up to the highest dose tested (1000 mg/kg). No indications of systemic availability could be obtained in this study. The bioaccumulation potential is therefore regarded as low.

For chemicals with a molecular weight < 100 dermal uptake is favored, while chemicals with a molecular weight > 500 have low potential to penetrate the skin (ECHA GD 7c, 2008). 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. In conclusion, systemic availability of the test article after dermal exposure is expected to be low. This is in line with the available guinea pig maximization test (Stillmeadow, 1994). None of the tested animals were sensitized after dermal exposure, therefore no indications for dermal penetration were evident in this study.

No data from acute or repeated dose toxicity studies by the inhalation route are available which could provide information about the systemic distribution of the test substance after inhalation. Inhalative exposure to vapors is not of relevance as the substance has a very low vapor pressure (0.0000014 Pa at 25°C). The test article agglomerates and therefore exposure to dust particles is expected to be low.

Metabolism

Using the OECD toolbox v. 3.0, the liver metabolism simulator provided 4 potential metabolites. In general, the liver simulator predicted hydroxylation of the aromatic ring and of the nitrogen atom. Studies on genotoxicity (Ames-Test, chromosome aberration assay) gave no indications of a reactivity of test substance or its metabolites under the test conditions (i.e. no increased mutagenicity or cytotoxicity in treatments with metabolic activation).

 

Excretion

The excretion pathway is largely dependent on molecular size, polarity and water solubility. The parent compound is expected to be excreted mainly via feces. Potential metabolites are either excreted via feces or urine, depending on their molecular size and water solubility after phase II metabolism.