Registration Dossier

Administrative data

Link to relevant study record(s)

Description of key information

No expected bioavailability neither orally, dermally nor inhalative was suggested. No bioaccumulation potential assumed. The test substance is expected not to be metabolized in the body due to low solubility in both water and fat. Further, excretion was concluded to occur via feces. However, no experimental data concerning absorption, distribution, and metabolism have been conducted.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
0
Absorption rate - dermal (%):
0
Absorption rate - inhalation (%):
0

Additional information

Assessment of the Toxicokinetic Behavior

The test substance is a red-violet solid dyestuff with a density of 1.584 g/cm3 at 20°C and a molecular weight of 390 g/mol. The test article has a low vapor pressure of < 0.000001 hPa at 20°C and is characterized by very low solubility in both water (0.01 mg/l at 20°C) and organic solvents (n-octanol: < 70 µg/L). The log Pow of 0.85 could only be calculated due to the lack of solubility. No studies are available investigating the toxicokinetic properties of the test substance. The toxicokinetic behavior is therefore assessed based on physico-chemical properties and on available toxicity studies performed with the test article and with other members of the category (for category justification refer to the attached document).

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 10,000 mg/kg body weight (BASF, 1978). None of the animals died during the exposure period. Clinical signs included agonal respiration at the beginning of the observation period. No abnormal findings were made at necropsy. Similar results were obtained in a second acute oral toxicity study during which rats (5/sex/dose) were administered the test substance at a single dose of 10,000 mg/kg body weight by gavage (BASF, 1976). None of the animals died during the exposure period. Clinical signs included dark red coloring of the skin and dark red coloring of the feces. No abnormal findings were made at necropsy. The results of both studies do not indicate any systemic availability of the test substance upon oral ingestion. In a recent reproduction / developmental toxicity screening study performed with the test article, no toxic effects were observed up to the highest dose level tested (1000 mg/kg bw). This result supports the proposed lack of absorbance. The observation of colored feces indicates that the substance is excreted unchanged. 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 performed with a structural analogue, no signs of toxicity were observed with the limit dose of 2500 mg/kg, indicating a low systemic availability after dermal exposure. 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 indications for absorption after inhalation are given from the available toxicity data and the physico-chemical properties of the test article. In two inhalation risk tests, the toxicity of an atmosphere that has been saturated at 20 °C with dust of the compound was investigated. Two groups of rats (3/sex/group) were exposed sequentially to the dusts for 7 to 8 h. None of the animals died during the exposure period and no abnormal clinical signs were reported. Body weights and gross pathology were normal (BASF, 1978 and 1976). Particle size distribution analysis showed that 64% of the analyzed material was smaller than 100 µm and 18% 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. 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, as indicated by the acute inhalation toxicity study and based on the very low solubility, particles are expected to be not absorbed and not bioavailable.

Metabolism

Considering the chemical structure of the test article, Cytochrome P450 linked oxidations of the aromatic ring systems are possible steps in the metabolism of the test article. However, based on the low solubility property in both water and fat, the substance is most likely not absorbed and excreted unchanged. This is supported by the observation of colored feces in toxicity studies. The substance was tested negative in genotoxicity tests (Ames test, Hoechst, 1983, HPRT, BASF, 2012), 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. This assumption is strengthened by the observation of colored feces in the toxicity studies. Overall, accumulation of test material within the body is not expected.