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Diss Factsheets

Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
no data available
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well documented and scientifically acceptable.

Data source

Reference
Reference Type:
publication
Title:
Kinetics of calcium, strontium, barium, and radium in rats
Author:
Domanski, T.; et al.
Year:
1969
Bibliographic source:
In: Mays, C.F.; et al. (Eds.): Delayed Effects of Bone-Seeking Radionuclides, Univ. of Utah Press, 79-94

Materials and methods

Objective of study:
distribution
excretion
other: retention
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The distribution, retention and excretion of different radionuclides administered in a single i.v. dose per test animal were determined.
GLP compliance:
no

Test material

Constituent 1
Reference substance name:
Calcium
EC Number:
231-179-5
EC Name:
Calcium
Cas Number:
7440-70-2
IUPAC Name:
calcium
Details on test material:
- Name of test material (as cited in study report): Calcium ion (unspecified)
No further details are given.
Radiolabelling:
yes
Remarks:
45Ca radioisotopes

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 8 months old
- Diet: For several weeks before and throughout the experiment, the rats were fed a diet containing 0.5 % Ca and 0.5 % P.
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
No further details are given.

Administration / exposure

Route of administration:
intravenous
Vehicle:
other: acetate buffer solution of pH 4
Details on exposure:
no data
Duration and frequency of treatment / exposure:
single administration
Doses / concentrations
Remarks:
Doses / Concentrations:
Group I: 16 µCi of 45Ca and 5 µCi of 85Sr;
Group II: 0.8 µCi 85Sr and 1.7 µCi 133Ba;
Group III: 0.75 µCi 226Ra.
No. of animals per sex per dose / concentration:
120 albino rats were used in total.
Control animals:
not specified
Positive control reference chemical:
No positive control substance was tested.
Details on study design:
- Dose selection rationale: no data
- Rationale for animal assignment (if not random): no data
Details on dosing and sampling:
PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: urine, faeces, blood, plasma and other tissues, bones
- Time and frequency of sampling: The animals were sacrificed serially in ether narcosis at 1, 2, 4, 6, 12, 18, 24, 48, 96 and 408 or 432 hours after administration of the isotopes. Blood was withdrawn at death, and the plasma was obtained by centrifugation in the presence of heparin.
From each animal at least one femur and one tibia were sampled for calcium assay and activity measurements.
Urine and faeces were collected quantitatively in metabolic cages in selected 20 hour periods from the first through the sixteenth day after injection of the radionuclides.
- Other: Plasma, bones, urine, faeces and in some cases whole carcasses were wet ashed with nitric acid and hydrogen peroxide, diluted to a constant volume, and appropriate aliquots analysed for stable calcium by the method of Bett and Fraser. The total and specific activity of 45Ca in the whole body was determined from beta-counting of the wet-ashed bones and the residual carcasses, corrected for self-absorption and radioactive decay.

METABOLITE CHARACTERISATION STUDIES
not examined
Statistics:
no data

Results and discussion

Preliminary studies:
not performed

Toxicokinetic / pharmacokinetic studies

Details on absorption:
not examined
Details on distribution in tissues:
The calcium concentration in plasma was close to 100 µg/mL (mean value of 100.4 µg/mL for all groups). It appears that 24 hours after injection, the radioactivity per g Ca in the plasma fell off exponentially.
One day after injection, the retention of the 3 elements Ca, Ba, and Sr was almost identical; later, however, the strontium tracer disappeared from the body faster than did those of calcium and barium.
After 96 hours the highest retention in the bones was that for 133Ba with values for the other isotopes in the decreasing order 45Ca > 226Ra > 85Sr. At that time, levels in the tibiae were consistently lower than in the femora, by 10 to 35 % for all the elements studied. The relative retention for the different radionuclides in single bones is similar to that for whole-body retention.
Details on excretion:
The average urinary excretion of calcium over a 16 day period was 0.044, 0.062 and 0.058 mg/hour in group I, II and III, respectively.
The corresponding values for the total faecal calcium were 1.42, 1.02 and 1.47 mg/hour. The endogenous faecal calcium in group I was 0.05 mg/hour.

Metabolite characterisation studies

Metabolites identified:
not measured
Details on metabolites:
not examined

Applicant's summary and conclusion