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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 black solid dyestuff with a relative density of 1.427 at 20°C and a molecular weight of 598 g/mol. The test article has a vapor pressure of < 0.000001 hPa at 20°C and is characterized by very low solubility in both water (< 2 µg/l at 20°C) and organic solvents (n-octanol: 86 µg/L). The log Pow of 1.6 at 23°C was calculated on the basis of the solubility in water and octanol. 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 other members of the category (for category justification see 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 oral toxicity study, rats (5/sex/dose) were treated with the test substance at a dose level of 5000 mg/kg bw by single dose (gavage) followed by a 14-day observation period (BASF AG, 1979). None of the animals died during the exposure period. All animals showed normal body weight gains and no abnormal findings were observed regarding clinical signs and at necropsy. In a 28-day oral repeated dose study (OECD guideline 407 and GLP), Sprague-Dawley rats (5/sex/dose) were administered the test substance at 750, 3750 and 15000 ppm in the diet (Safepharm Laboratories Ltd, 1990). None of the animals died during the study. No clinically observable signs of toxicity were noted in test or control animals throughout the study. Black feces were common to all treatment groups. Bodyweight gain in all test animals was comparable with that seen in controls. There were no treatment-related changes in food consumption and food efficiency during the study. Some changes in clinical chemistry were noted, but these changes were either slight, not dose related or within the historical controls. No treatment-related differences in organ weight were detected between test and control animals. The NOAEL was therefore set at the highest dose level, i.e., at 15000 ppm / 1573 mg/kg and 15000 ppm / 1501 mg/kg bw/day for male and female rats, respectively. The lack of systemic toxicity in these studies suggests poor bioavailability upon oral ingestion. As a result an accumulation of the test article in the body is not expected.

 

Dermal absorption is equally unlikely based on the test compound’s very low solubility properties in both water and fat. In addition, substances with a molecular weight of greater than 500 may be too large for dermal uptake. In a dermal toxicity study performed with a structure 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 physic-chemical properties of the test article. In an inhalation risk test performed with the test substance (BASF, 1978), the toxicity of an atmosphere that has been saturated at room temperature with dust of the compound was investigated. Two groups of rats (3/sex/group) were exposed sequentially to the dusts for 7 h. None of the animals died during the exposure period and no abnormal clinical signs were reported. Body weights and gross pathology were normal. Particle size distribution analysis showed that 100% of the analyzed material was smaller than 100 µm and 61.8% 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. However, based on the low solubility property in both water and fat, the substance is most likely not absorbed and excreted unchanged, supported by the observation of colored feces. Studies on genotoxicity (Ames assays, BASF, 1991, Litron, 1985 and in vitro cytogenetics, BASF, 1989) were negative, 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 predominantly via the feces. This assumption is strengthened by the observation of dark colored feces in the toxicity studies. Overall, accumulation of test material within the body is not expected.