Registration Dossier

Diss Factsheets

Toxicological information

Basic toxicokinetics

Currently viewing:

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:
Dynamics of 241Am in the skeleton of the rat: A study of the relationsship betwenn behavior of bone-seeking elements and bone-growth status
Author:
Durbin, P.W.; et al.
Year:
1969
Bibliographic source:
In: Mays, C.F.; et al. (Eds.): Delayed Effects of Bone-Seeking Radionuclides, Univ. of Utah Press, 137-156

Materials and methods

Objective of study:
distribution
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Behaviour of 241Am and 45Ca in the skeleton and growth and senescence of the skeleton of female rats.
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

Test animals

Species:
rat
Strain:
other: CRCD
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: rats free of disease raised by Charles River Breeding Laboratories, North Wilmington, Massachusetts
- Age at study initiation: 11 days
- Individual metabolism cages: yes
No further details are given.

Administration / exposure

Route of administration:
intramuscular
Vehicle:
other: isotonic sodium citrate
Details on exposure:
Isotopes were diluted with isotonic sodium citrate and administered to rats.
Duration and frequency of treatment / exposure:
single exposure; effect observations: 180 days after injection
Doses / concentrations
Remarks:
Doses / Concentrations:
241Am: 0.1 µCi/rat;
45Ca: 10 µCi/rat
No. of animals per sex per dose / concentration:
45Ca: 8 female rats housed in individual cages
241Am: 4 groups of rats (three rats per cage)
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 and other tissues
- Time and frequency of sampling: excreta were collected from Ca-injected rats.
Soluble soft tissue ash was removed from insoluble bone ash by gentle rinsing with alkaline water. Rinse from each rat carcass was analysed as a separate sample designated "soft tissue balance".
- Other: Three radiochemical procedures were used: a) 45Ca and 241Am in ashed excreta were precipitated as oxalates according to the method of Comar. b) Bone and tissue ash were evaporated on glass plates as Ca3(PO4)2, according to the method of Barr. c) When Am levels in excreta were very low, Am was first concentrated by the oxalate method, then redissolved and coprecipitated with LaF3 as described by Scott et al.
Bones were fixed in 80% alcohol, sawed, dehydrated in alcohol and acetone, and embedded in Bioplastic. Autoradiographs were prepared by exposure to X-ray film, NTA plates and spectrographic plates.

METABOLITE CHARACTERISATION STUDIES
not examined
Statistics:
no data

Results and discussion

Preliminary studies:
not performed

Toxicokinetic / pharmacokinetic studies

Details on absorption:
no data
Details on distribution in tissues:
45Ca kinetics: After 45Ca injection 4 general processes were identified - their rates were sufficiently different to be distinguishable:
- Component A1 (T1/2 = 2 to 4 days) was attributed to early exchange loss of diffuse label;
- Component A2 (T1/2 = 20 to 30 days) was associated with resorption during growth remodeling;
- Component A3 (t1/2 = 150 to 300 days) was related to slow growth remodeling as in rip and mandible and maintenance remodeling in long bones and vertebrae;
- Component A4 (T1/2 = 2600 days) was associated with cortical bone remodeling and structural loss in very old age.
The recirculation of 45Ca is demonstrated by continued deposition in incisors and in metaphysal trabeculae formed during the first 180 days PI. When 45Ca enters bone, it partitions between diffuse deposition in pre-existing bone and concentrated deposition in regions of new bone formations.
Details on excretion:
no data

Metabolite characterisation studies

Metabolites identified:
not measured
Details on metabolites:
not examined

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): bioaccumulation potential cannot be judged based on study results
Early exchange loss of diffuse label, resorption during growth remodeling,
Redistribution trend of Ca was mainly towards new bone formation in temporary bony structures

Categories Display