1,1'-[(6-phenyl-1,3,5-triazine-2,4-diyl)diimino]bisanthraquinone

Endpoint summary

Additional information

Assessment of the Toxicokinetic Behavior

The test substance is a yellow powder with a density of 1880 g/cm³at 23°C and a molecular weight of 600 g/mol. Based on the melting point of > 400°C, the vapor pressure was not determined, but it is anticipated to be very low. The test item is furthermore characterized by very low solubility in both water (< 0.01 mg/l at 23°C) and fat (19 µg/l in n-Octanol). The log P_ow of 0.3 was determined at 23°C and pH 6.4. No studies are available investigating the toxicokinetic properties of the test substance. The toxicokinetic behavior is therefore assessed based on physic-chemical properties and on available toxicity studies performed with the test article.

Absorption

Based on the very low water solubility and the low solubility in n-octanol (i.e. fat), bioavailability of the test substance is generally not expected. This is supported by the available toxicity studies. In an acute oral toxicity study male and female rats were given a single oral dose (gavage) of the test article at a concentration of 6000 mg/kg body weight (BASF, 1973). None of the animals died during the exposure period. Clinical signs included sedation, dyspnoe and ruffled fur and curved body position, being common symptoms in acute tests. No abnormal findings were made at necropsy. In a recent combined repeated dose toxicity study with the reproduction / developmental toxicity screening performed with the test article, no toxic effects were observed up to the highest dose level tested (Charles River, 2015). These results support the assumed low bioavailability due to low absorbance. Accumulation of the test article in the body is therefore not expected.

Dermal absorption is equally unlikely based on the test compound’s very low solubility properties in both water and fat. In a dermal toxicity study no signs of toxicity were observed with the limit dose of 2000 mg/kg, indicating a low systemic availability after dermal exposure (Bioassay, 2013). In conclusion, based on the low water solubility together with the results of acute dermal toxicity studies, dermal absorption of the test article is not expected.

No valid inhalation study is available with the test article. Particle size distribution analysis showed that 100% of the analyzed material was smaller than 100 µm and 14% of the substance was found in particles smaller than 10 µm. These data demonstrate that the test substance can be inspired and may reach the alveolar region upon dust inhalation, at least to some extent. However, since the test article is neither soluble in water nor soluble in fat, absorption and systemic availability after inhalation is not expected. Particles deposited in the nasopharyngeal region will most likely be coughed or sneezed out and particles deposited in the trachea-bronchial region will be cleared by mucocilliary mechanisms and swallowed. Dust particles reaching the alveolar region will mainly be engulfed by alveolar macrophages and cleared via the ciliated airways or the lymphatic drainage. In conclusion, the test article can be inspired in the form of dust, however, based on the very low solubility, particles are expected to be not absorbed and not bioavailable.

Metabolism

Based on the low solubility property in both water and fat, the substance is most likely not absorbed and excreted unchanged. The substance was tested negative in various genotoxicity tests, i.e. there is no indication of a reactivity of the test substance or its metabolites with biomacromolecules under the chosen test conditions.

 

Excretion

Since the test article is not soluble in water and fat, excretion is expected to occur via the feces. Accumulation of test material within the body is not expected.