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EC number: 266-564-7
CAS number: 67075-37-0
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.
Assessment of the
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).
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.
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.
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.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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