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EC number: 233-296-7 | CAS number: 10108-64-2
- 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: other routes
Administrative data
- Endpoint:
- sub-chronic toxicity: other route
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- no information
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Reliable with restriction. Well documented. Not according to GLP nor to specific test guideline
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to other study
Data source
Reference
- Reference Type:
- publication
- Title:
- Cadmium-induced osteomalacic and osteopetrotic lesions inovriectomised rats
- Author:
- Katsuta O, Hiratsuka H, Matsumoto J, Iwata H, Toyota N, Tsuchitani M, Umemura T and Marumo F
- Year:
- 1 994
- Bibliographic source:
- Toxicol. Appl. Pharmacol.126:58-68
Materials and methods
- Principles of method if other than guideline:
- The repeated exposure effect of the test material on the bones of rats were determined. Young, ovariectomised, growing female rats were administered cadmium chloride intravenously (1.0 or 2.0 mgCdCl2/kg, 5 d/wk during 13 wk). General clinical observations, body weights and relevant serum levels were measured. Femurs and humerus were examined upon autopsy.
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- Cadmium chloride
- EC Number:
- 233-296-7
- EC Name:
- Cadmium chloride
- Cas Number:
- 10108-64-2
- Molecular formula:
- CdCl2
- IUPAC Name:
- cadmium(2+) dichloride
- Details on test material:
- -Name of test material-CdCl2
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Japan, Kanagawa, Japan
- Age at study initiation: 4 wk
- Housing: polycarbonate cage in a barrier system
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-25
- Humidity (%): 40-70
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- intravenous
- Vehicle:
- physiological saline
- Details on exposure:
- None
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 13 wk
- Frequency of treatment:
- 5 d/wk
Doses / concentrations
- Remarks:
- Doses / Concentrations:
1 and 2 mg/kg/d
- No. of animals per sex per dose:
- 18
- Control animals:
- yes
- Details on study design:
- Post-exposure period: 4, 8 and 13 wk after the treatment was commenced; 6 animals per group were sacrificed
Examinations
- Observations and examinations performed and frequency:
- PARAMETERS ASSESSED DURING THE STUDY
- Clinical observations performed and frequency: body weight frequency: weekly
- Autopsy: microscopic and macroscopic examination: femur, humerus - Statistics:
- Dunnett's t test multiple comparisons test
Results and discussion
Results of examinations
- Clinical signs:
- not specified
- Mortality:
- not specified
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- effects observed, treatment-related
- Behaviour (functional findings):
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- not specified
- Details on results:
- TOXIC RESPONSE/EFFECTS BY DOSE
- Body weight: In 2.0 mg/kg group growth retardation was prominent from 2 to 13 wk consistently, weight loss clear from 8 wk. In the 1.0 mg/kg group, decrease of body weight from 10 wk
- Food/water consumption: no information
- Description, severity, time of onset and duration of clinical signs: no information
- Ophthalmologic findings incidence and severity: no information
- Haematological findings incidence and severity: no information
- Clinical biochemistry findings incidence and severity:
* Blood: decreased hematocrit, Hb, MCV, MCH in the 2.0 mg/kg group at 8 and 13 wk. Increases of AST, ALT in the 2.0 mg/kg group at 13 wk, increase in total protein from 4 to 13 wk. Increases in serum concentrations of Ca and inorganic P in the 2.0 mg/kg group at 8 and 13 wk. Those changes were less pronounced in the 1.0 mg/kg group.
* Urine: Increase of water consumption and urine volume. NAG and gamma-GT values were markedly increased in treated rats as was the Ca excretion. No dose-dependent change between the 2 dose groups.
* Hormone assays: serum levels of PTH and BGP were not significantly different between treated and control animals
- Mortality and time to death: no information
- Gross pathology incidence and severity: mild fibrosis of the liver and foci of scarring on the kidney found in the 2.0 mg/kg group. No significant difference between the 2 groups in femur length
- Organ weight changes: no information
- Histopathology incidence and severity: Cd –treated rats
Kidneys: vacuolations of proximal convoluted tubular epithelium, single-cell necrosis and/or regeneration of the epithelial cells observed in teh outer cortical zone at 4 wk. Thereafter, multifocal lesions of tubular atrophy with interstitial fibrosis were distributed throughout this zone. Increased number of coagulating necrotic cells and hypertrohy of collecting tubular epithelium at 13 wk. Incidence and severity of these changes more pronounced in the 2.0 mg/kg group.
Bone: lesions were restricted to the distal portion of the femur and in the proximal portion of the tibia. Cortical bone: dilated haversian canals and surrounded by an increased amount of uncalcified matrix: osteoid seams.
Thickness of the cortical bone was almost normal. In the metaphysis of Cd-treated rats cancellous bone mass increased with time. Trabeculae were thickened and cohered to each other and formed an increased opacity beneath the metaphyseal plates. Changes were more frequent and more severe in the 2.0 mg/kg group. In the 2.0 mg/kg group a slight increase of osteoid seams was also observed in the trabecular bone of the lumbar vertebra of 2 rats at 13 wk.
Liver: diffuse increase of hepatocytic eosinophilia and a few foci of single-cell necrosis of hepatocytes at 4 wk. At a later stage, periportal hepatitis was detected with piecemeal necrosis in the limiting plate, especially in the 2.0 mg/kg group.
No lesions detected in the control rats
Cd, MT, Ca and P contents of organs: hepatic and renal concentrations of Cd and MT increased with dose dependency at 4 wk and the concentrations were not much different between the 2 dose groups. Cd absent in organs of control group. Bone content of Cd increased gradually until termination of the experiment. Concentrations of Cd and P in controls and exposed rats were not different.
Effect levels
- Dose descriptor:
- NOAEL
- Basis for effect level:
- other: Bone toxicity at high dose. Results do not allow discrimination of whether bone effects are due to direct action of cadmium on bone tissue or are a consequence of kidney damage
- Remarks on result:
- not determinable
- Remarks:
- no NOAEL identified
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
None
Applicant's summary and conclusion
- Conclusions:
- Although an involvement of the indirect action of Cd through renal failure could not be ruled out in this experiment, the biochemical and pathological data suggested that osteomalacia was induced by a direct action of Cd on the bone through abnormal calcium homeostasis
- Executive summary:
The repeated exposure effect of the test material on the bones of rats were determined.
Young, ovariectomised, growing female rats were administered cadmium chloride intravenously (1.0 or 2.0 mg CdCl2/kg, 5 d/wk during 13 wk).
This treatment produced severe nephropathy evidenced pathologically by tubular atrophy and interstitial fibrosis as well as clinically by enzymuria and polyuria. The skeletal changes were detected mainly in the femur and tibia where osteomalacic and osteopetrotic changes were detected. Relevant serum hormone levels were not modified by the treatment.
Overall, this study demonstrates the bone toxicity of very high doses of Cd. The results do not allow discriminating whether the bone effects observed are due to a direct action of Cd on the bone tissue or are an indirect consequence of kidney damage (renal osteodystrophy).
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