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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 1.47 at 20°C and a molecular weight of 630.7 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: 40 µg/L). The log Pow of 1.3 at 20°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 physic-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 oral toxicity study comparable to OECD guideline 401, five Wistar rats per sex were treated with the test article at a single dose of 5000 mg/kg bw by gavage followed by a 14-day observation period (BASF AG, 1982). None of the animals died during the exposure period. At day 1 and 2 of the observation period the feces were blue. The animals showed a normal body weight gain. No abnormal findings were observed at necropsy. Therefore, based on the results of this study, the LD50 was determined at greater than 5000 mg/kg body weight. This result does not indicate any systemic availability of the test substance upon oral ingestion. In addition, various oral toxicity studies with repeated administration have been performed with structural analogues of the same category. None of them revealed any toxicity up to the highest dose levels tested (1000 mg/kg bw and up). These results support the proposed lack of absorbance for the members of this category. 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 toxicity study comparable to OECD guideline 403, Wistar rats (10/sex) were exposed to the test article as dust for 4 hours at a measured concentration of 5.4 mg/L followed by a 14-day observation period (BASF, 1983). None of the animals died during the study period. Clinical signs included erratic breathing, slight nasal excretion and ragged fur during the first 4 days of the observation period, no abnormal findings were observed from day 5 onward. No abnormal findings were noted at necropsy. The mass median aerodynamic diameter (MMAD) was 1.9 µm (GSD: 3.9), which is well within the respirable range. An additional particle size distribution analysis showed that 83.2% of the analyzed material was smaller than 100 µm and 4.3% 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. This is supported by the observation of colored feces in toxicity studies. Studies on genotoxicity (Ames assays, BASF, 1981 and 2008) 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 colored feces in the toxicity studies. Overall, accumulation of test material within the body is not expected.