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EC number: 231-166-4 | CAS number: 7440-58-6
- 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
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
Data source
Reference
- Reference Type:
- publication
- Title:
- The metabolism of radiohafnium in marmosets and hamsters
- Author:
- Taylor DM, Siedel A, Doerfel H
- Year:
- 1 985
- Bibliographic source:
- International Journal of Nuclear medecine and biology, 12 (5): 387-391
Materials and methods
- Objective of study:
- toxicokinetics
- GLP compliance:
- yes
Test material
- Reference substance name:
- Hafnium
- EC Number:
- 231-166-4
- EC Name:
- Hafnium
- Cas Number:
- 7440-58-6
- Molecular formula:
- Hf
- IUPAC Name:
- hafnium
- Details on test material:
- For Chinese hamsters: 181Hf from Amersham, Buchler, Braunschweig FRG 40 kBq (ca. 1 MBq/kg)
For marmosets: 181Hf-citrate form Amersham, Bh=uchler, Braunschweig FRG 3 kBq (ca. 10 kBq/kg)
Constituent 1
- Radiolabelling:
- yes
- Remarks:
- 181Hf
Test animals
- Species:
- other: Chinese hamsters and marmosets
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Chinese hamsters were bred in the institute for breeding pairs obtained from the Bundesforschungsandstalt für Ernährung, Karlsruhe FRG. They were maintained on a pellet diet, with food and water provided ad libitum.
Marmosets (Callithrex jacchus) came fromthe breeding stock of the Institute of Human Genetics, University of Heidelberg FRG. The animals were between 4 and 9 years old, they were maintained on marmosets pellets and various fresh fruits.
Administration / exposure
- Route of administration:
- other: hamsters: oral and subcutaneous / marmosets: intramuscular
- Vehicle:
- not specified
- Details on exposure:
- Hamsters: radiohafnium was administered orally by placing 10 µL of solution on the back of the tongue or subcutaneously by injection of 0.2 cm3 of solution under the skin of the back.
Marmosets were injected intramusculary into the right thigh with 3 kBq of 181Hf-citrate. - Duration and frequency of treatment / exposure:
- the four marmosets were studied by whole body counting for up to 182 days after injection
Doses / concentrations
- Remarks:
- Doses / Concentrations:
For Chinese hamsters: 40 kBq (ca. 1 MBq/kg)
For marmosets: 3 kBq (ca. 10 kBq/kg)
- No. of animals per sex per dose / concentration:
- marmosets: 2 males and 2 females
hamsters: not mentioned - Details on dosing and sampling:
- Measurement of radioactivity in marmosets
The in vivo measurements were realised in the human whole bidy counter. This device consists of four 20 cm dia. x 10 cm thick NaI (Tl) scintillation detectors set up in pairs above and below a stretcher. In order to achieve standard measuring conditions, the animals were counted insteel cages, positioned in the geometrical centre between the detectors and counted for 10 min each. For determination of the 181Hf activity, the predominant 482keV gama peak was evaluated. The measuring device was calibrated with 181Hf standard sources positioned at representative places within the steel cages, this calibration showed the lower detection limit to be about 30Bq 181Hf. The error due to the calibration and the positioning of the animals is about +/- 15 %.
Measurement of radioactivity in rats
The measurements of whole body radioactivity in the hamsters were made in a small-animal-whole-body counter consisting of two opposing 13 cm dia. 10 cm thick NaI(Tl) crystal detectors contained in a lead and steel shield.
Each animal was counted first within 30 min of radionucleide injection and at daily or longer intervals thereafter. On each occasion, an aliquot of the injection solution was counted in order to correct for radioactivity decay and small changes in the efficiency of the counter. The initial count on each animal was taken as 100 % for the purpose of calculating the percentage retention at later times.
Measurement of radioactivity in tissue samples
Tissue samples from marmosets and hamsters were assayed by scintillation counting in an automatic gama scintillation counter.
Results and discussion
- Preliminary studies:
- During the course of the study, 2 animals (1 male and 1 female marmosets) became ill and had to be humanely killed at 13 and 97 day post injection, the nature of the progressive disease which appeared to involve a fatty degeneration of the liver has not been established.
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- Absorption was calculated by using a correction factor for excretion based on the whole body retention of 71 % +/- 1 % in 10 rats given 181Hf citrate by sc injection 7 days previously.
Absorption (%) of 135+181Hf from the gastro-intestinal tract of Chinese hamster
- Hf chloride pH6, 1 µg/kg, fasted 18h: between 0.05 and 0.09 % dose +/- 0.01 %
- Hf chloride in 0.2 M HCl (1 µg/kg pH2): 0.13 % +/- 0.01 %
- Hf in "orange juice" (1 µg/kg pH4): 0.05 % +/- 0.01 %
- Hf citrate (1 µg/kg pH 7): 0.09 % +/- 0.01 % - Details on distribution in tissues:
- Distribution
- Details on excretion:
- The retention data for the marmosets could be fitted to a two component exponential function
R = 42 exp-0.39t + 66exp-0.0021t
where t is the time after injection in days, and R the amount of 181Hf retained in per cent of the injected dose.
Whole body retention in hamsters was measured in the whole body counter at daily or longer intervals for 28 days at which time the animals were killed and the retention in the various organs and tissues was measured: 4.7 % +/- 0.2 in liver, 0.76 % +/- 0.05 in kidneys, 0.18 % +/- 0.02 in spleen, 3.5 % +/- 0.3 in muscle, 12 % +/- 2 in skin and 25 % +/- 2 in skeleton, total body 62.6 % +/- 2.8.
Metabolite characterisation studies
- Metabolites identified:
- not measured
Any other information on results incl. tables
Distribution of intramuscularly injected 181Hf in the organs of marmosets, values represent percent of dose which was resorbed form injection site until day of sacrifice
day of | liver | femur | kidneys | spleen | lungs | ||||||
sacrifice | sex | % of dose | % /g | % of dose | % / g | % of dose | % / g | % of dose | % / g | % of dose | % / g |
13 | male | 8.3 | 0.5 | 1.1 | 0.9 | 4.3 | 1.9 | 0.2 | 0.2 | 0.3 | 0.8 |
97 | female | 12.1 | 0.7 | 0.7 | 0.7 | 1.5 | 0.8 | 0.2 | 0.7 | 0.3 | 0.2 |
Applicant's summary and conclusion
- Executive summary:
Hf is poorly soluble in water or saline solutions: thus, it is not absorbed efficiently by ingestion. This study, realized with radiohafnium, found an oral absorption ranging between 0.04 and 0.13 % of the ingested dose in Chinese hamsters. It can be absorbed by inhalation only under its aerosol form.
In hamsters, radiohafnium was administered subcutaneously by injection of 0.2 cm3of the solution (40 kBq) under the skin of the back. The radiohafnium organ distribution was skeleton greater than skin greater than liver greater than muscle, at about 7 days post injection.
Four marmosets, 2 females (aged 4 and 8 years) and 2 males (aged 6 and 9 years), exposed to radiohafnium, were also studied. They were injected intramuscularly into the right thigh with 3 kBq. For males and females, sacrificed respectively after 13 and 97 days, the following percentages of doses found in different organs were: in liver,8.3-12.1 % of the dose injected, bones around 1 % measured in the femur; in the kidneys, 1.5-4.3 %; and in a lesser extent in spleen and lung.
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