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EC number: 474-260-2 | CAS number: 22841-92-5
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- other information
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 007
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: 96/54/EG, B.7; OECD 407 (1995) Siehe Bemerkungen.
- GLP compliance:
- yes
- Limit test:
- no
Test material
Constituent 1
Test animals
- Species:
- other: rat, Crl:CD(SD)
- Sex:
- male/female
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: 0,5 % Methylcellulose
- Details on oral exposure:
- Method of administration:
gavage - Duration of treatment / exposure:
- Test duration: 28 days
- Frequency of treatment:
- Dosing regime: 7 days/week
- No. of animals per sex per dose:
- Male: 5 animals at 5 mg/kg bw/day
Male: 5 animals at 15 mg/kg bw/day
Male: 5 animals at 50 mg/kg bw/day
Male: 5 animals at 100 mg/kg bw/day
Female: 5 animals at 5 mg/kg bw/day
Female: 5 animals at 15 mg/kg bw/day
Female: 5 animals at 50 mg/kg bw/day
Female: 5 animals at 100 mg/kg bw/day
Results and discussion
Results of examinations
- Details on results:
- Clinical observations:
Test substance-related death occurred at 100 mg/kg bw/d.
The 100 mg/kg bw/d dose group was terminated on day 17 due
to the test substance-related mortality and clinical signs
of severe toxicity within the group. Two males were found
dead on days 12 and 16, and one female was sacrificed in
extremis on day 13. Two females were accidentally killed,
one on day 2 (immediately after dosing), and one on day 3
(found dead), due to a dosing accident. The remainder three
males and two females were sacrificed on day 17 because of
severe toxic signs.
Clinical signs were noted approximately 1-3 hours post-
dosing on day of sacrifice or found dead and included
aggressive behaviour, convulsions, hypersensitivity,
hyperreactivity, salivation, and tremors. Test substance-
related adverse decrease in food consumption in animals at
100 mg/kg bw/d corresponded to reduced body weights and
mean body weight gains in animals treated at this dose
level. At 50 mg/kg bw/d adverse test substance-related
decreases (compared to controls) in mean body weights
(males / females: 6 - 13 % / 8 - 10 %), mean body weights
gains (males / females: 30 - 50 % / 29 - 60 %), and food
efficiency (males / females: 20 - 30 % / 30 - 40 %) were
observed in males and females. Food consumption was not
affected at this dose level.
No test substance-related effects were detected during
functional observational battery and motor activity
measurements in males and female receiving 50 mg/kg bw/d
and below.
Laboratory findings:
Haematology revealed statistically significant decreased
red blood cell counts (RBC), haemoglobin and hematocrit
values in parallel to significantly increased reticulocyte
counts for males and females at 15 and 50 mg/kg bw/d (except
for RBC, not significant in 15 mg/kg bw/d males; except for
reticulocyte count, not significant in 15 mg/kg bw/d
females). In males, statistically significant decreased
haemoglobin and hematocrit values were also noted at
5 mg/kg bw/d. Furthermore, statistically significant
decreased MCHC values were seen for males at 50 mg/kg bw/d
and for females at 15 and 50 mg/kg bw/d; statistically
significant increased red cell distribution width (RDW) was
determined for males at 15 and 50 mg/kg bw/d and for females
at 50 mg/kg bw/d. These haematology findings correlated with
histopathological findings of erythrocytic hyperplasia in
the bone marrow, and increased extramedullary haematopoiesis
in the spleen and liver.
Test substance-related adverse changes of clinical
biochemistry parameters suggestive of decreased glomerular
filtration in the kidney were present in males and/or
females treated with 50 mg/kg bw/d. These were statistically
significant increased urea nitrogen (males: 133 % of
controls), increased creatinine (males / females: 136 % /
126 % of controls), and increased inorganic phosphorous
(males / females: 124 % / 119 % of controls). In addition,
statistically significant decreased calcium values (92 % of
controls) in males and increased chloride values in males
and females (102 % / 103 % of control) were noted at
50 mg/kg bw/d. Bilirubin was statistically significant
increased (158 % and 150 % of control, respectively) in
males and females at 50 mg/kg bw/d, and was also
statistically significant increased in females treated at
5 and 15 mg/kg bw/d.
Urinalysis revealed statistically significant increased
total protein values for males treated at 50 mg/kg bw/d.
Effects in organs:
Test substance-related effects were noted in organ weights
and gross as well as microscopic examination in liver,
kidneys, spleen and bone marrow in both sexes.
The assessment of organ weights showed statistically
significant increases in absolute and relative liver
(50 mg/kg bw/d), kidney (50 mg/kg bw/d males;
>= 15 mg/kg bw/d females) and spleen (>= 15 mg/kg bw/d)
weights in animals of both sexes.
At necropsy discolouration of the kidneys (>= 15 mg/kg bw/d
males, 100 mg/kg bw/d females) and discolouration and
enlargement of the spleen (>= 50 mg/kg bw/d males,
100 mg/kg bw/d females) were observed that correlated with
microscopic findings in these organs.
Microscopy revealed test substance-related effects in the
kidney, spleen, liver and bone marrow:
Kidney: Renal cortical tubular degeneration and/or necrosis
with regeneration (i.e., renal cortical nephrosis) was
observed in all male and female rats given >= 15 mg/kg bw/d
and in 4/5 females given 5 mg/kg bw/d. The severity was
dose-related and females were more affected than males.
The nephrosis was characterized by degeneration and necrosis
of individual or clusters of epithelial lining cells in
the proximal convoluted tubules of the renal cortex.
Evidence of a regenerative response included increased
mitotic figures, hypercellular tubules with cytoplasmic
basophilia (basophilic tubules), and karyomegaly.
Spleen:
Increased extramedullary haematopoiesis was observed in
males and females given >= 15 mg/kg bw/d. Both the
incidence and severity were dose-related. An increase in
the amount of hemosiderin pigment was present in all
10 rats given 50 mg/kg bw/d, and in 4/5 females given
15 mg/kg bw/d. Congestion of the red pulp was apparent in
males and females dosed with >= 15 mg/kg bw/d.
Liver: Centrilobular hepatocellular hypertrophy was
observed in 5/5 males and 5/5 females dosed with
50 mg/kg bw/d. Extramedullary haematopoiesis was observed
in 2/5 males and 2/5 females given 50 mg/kg bw/d. Increased
hemosiderin pigment in Kupffer cells was noted in 3/5 males
and in 5/5 females at 50 mg/kg bw/d.
Bone marrow:
An increase in erythrocytic hyperplasia was seen in
4/5 males and in 5/5 females at 50 mg/kg bw/d. The
hyperplasia correlated with increased red blood cell
haematopoiesis in spleen and liver as well as
haematology findings.
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- Classified as R48/25 - STOT RE1, H372
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.
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