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EC number: 225-590-9
CAS number: 4948-15-6
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
solid dyestuff with a density of 1.415 g/cm³
at 20°C and a
molecular weight of 599 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 (1.4 µg/l at 20°C) and organic solvents (n-octanol: 1.9
µg/L). The log Pow of
0.13 could only be calculated (based on the low solubilites). 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 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
ten female albino rats were treated with the test article at 15,000
mg/kg bw by single oral dose (gavage) followed by a 7-day observation
period (Hoechst AG, 1967). None of the animals died during the exposure
period. No abnormal clinical observations were observed; the pigment was
excreted via the feces. In another study ten female Wistar rats were
treated with the test article at 5000 mg/kg bw by single oral dose
(gavage) followed by a 14-day observation period (Hoechst AG, 1982).
None of the animals died during the exposure period. No abnormal
clinical observations were observed; the pigment was excreted via the
feces. A normal weight gain was observed and no abnormal findings were
made at necropsy. The subchronic toxicity of the test substance was
tested in crossbred albino rats in a 90 -day feeding trial. Three groups
Sprague-Dawley rats (15/sex/dose) were administered the test article at
0 (group III), 10,000 (group II) and 50,000 ppm (group I) in the diet
(Hoechst AG, 1967). The general behavior in groups I and II was normal
throughout the entire trial period and did not differ from that of the
control animals. None of the experimental animals showed signs of a
toxic effect. The test article was excreted via the feces. The food
consumption and the weight gains of the treated rats were normal and did
not differ from that of the control rats. The hematological
investigations revealed no pathological findings. Investigation of the
urine showed no pathological findings which could be attributed to the
test article administered. Macroscopic and microscopic examination
revealed no pathological organ damage. The lack of systemic toxicity in
these studies suggests poor absorption resulting in low or no
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 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 physic-chemical properties of the test article. In an inhalation
toxicity study according to OECD guideline 403, Wistar rats (5/sex) were
exposed to the test article as dust for 4 hours at a measured
concentration of 5.2 mg/L followed by a 14-day observation period (BASF
AG, 1989). None of the animals died during the study period. Clinical
signs included irregular, accelerated and/or intermittent respiration,
flight behavior and discolored fur. From day 7 of the observation period
onward, no abnormalities, except discolored fur, were detected in the
animals. The body weight gain of male and female rats in the test group,
compared with a historical control collective, was not affected by the
substance over the total observation period. No pathologic findings were
noted during gross pathology. Cascade impactor measurements performed
during this inhalation study resulted in a particle size distribution
with a mass median aerodynamic diameter (MMAD) of 3 µm (GSD: 3.6), which
is well within the respirable range. An additional particle size
distribution analysis showed that 99.3% of the analyzed material was
smaller than 100 µm and 14.9% 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 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
substance was tested negative in genotoxicity tests (Ames tests,
Hoechst, 1982 and BASF, 1998), 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
observations made during toxicity tests (colored feces). 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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