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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Long-term data on toxicokinetics for slags, ferronickel-manufg. is not available for the whole substance and is impossible to derive because of the nature of the substance. Being a UVCB, it consists of a number of different substances (mainly metals and metal oxides) that are bound together in a number of phases. Therefore it was attempted to identify possible adverse effects based on data for its recognised constituents, even though the results cannot be applied directly, due to the way the constituents are bound in the matrix of the substance and are not as bioavailable as the free substances that are examined (it is also supported by the low water solubility). So, the results must be taken into consideration with care. The object of this paper was to summarise the general principles and scope for the application of 26Al as a tracer to investigate human or animal biochemistry.

Data source

Reference
Reference Type:
publication
Title:
Biological chemistry of aluminium studied using 26Al and accelerator mass spectrometry
Author:
J.P. Day, J. Barker, S.J. King, R.V. Miller, J. Templar, J.S. Lilley, P.V. Drumm, G.W.A. Newton, L.K. Fifield , J.O.H. Stone , G.L. Allan , J.A. Edwardson , P.B. Moore, I.N. Ferrier, N.D. Priest, D. Newton, R.J. Talbot, J.H. Brock , L. S5nchez , C.B. Dobson, R.F. Itzhaki, A. RadunoviC and M.W.B. Bradbury.
Year:
1994
Bibliographic source:
Nuclear Instruments and Methods in Physics Research B, vol.92 (1994), pp. 463-468

Materials and methods

Objective of study:
other: absorption, distribution, excretion
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
A particular Test Guideline was not specified in the study.
GLP compliance:
not specified
Remarks:
Not applicable

Test material

Constituent 1
Reference substance name:
Aluminium
EC Number:
231-072-3
EC Name:
Aluminium
Cas Number:
7429-90-5
IUPAC Name:
aluminum
Details on test material:
Aluminium 27 isotope
Radiolabelling:
yes

Test animals

Species:
human
Strain:
not specified
Sex:
not specified
Details on test animals or test system and environmental conditions:
Studies on human volunteers.

Administration / exposure

Route of administration:
other: orally or via injection
Vehicle:
other: in excess of stable isotope and citrate solutions
Details on exposure:
i) ingestion of 26Al with excess amounts of the stable isotope 27Al and citrate carriers. Blood samples taken sequentially for determination of maximum plasma levels, gastrointestinal uptake factor, speciation in blood. 26Al measured by accelerator mass spectrometry ii) injection of 26Al in citrate solution. Whole body measurements by gamma spectroscopy for determination of retention t1/2, volume of distribution
Duration and frequency of treatment / exposure:
single exposure, no further data
Doses / concentrations
Remarks:
Doses / Concentrations:
no information
No. of animals per sex per dose / concentration:
no information
Control animals:
no
Positive control reference chemical:
not applicable
Details on study design:
i) ingestion of 26Al with excess amounts of the stable isotope 27Al and citrate carriers. Blood samples taken sequentially for determination of maximum plasma levels, gastrointestinal uptake factor, speciation in blood. 26Al measured by accelerator mass spectrometry ii) injection of 26Al in citrate solution. Whole body measurements by gamma spectroscopy for determination of retention t1/2, volume of distribution
Details on dosing and sampling:
i) ingestion of 26Al with excess amounts of the stable isotope 27Al and citrate carriers. Blood samples taken sequentially for determination of maximum plasma levels, gastrointestinal uptake factor, speciation in blood. 26Al measured by accelerator mass spectrometry ii) injection of 26Al in citrate solution. Whole body measurements by gamma spectroscopy for determination of retention t1/2, volume of distribution
Statistics:
no data

Results and discussion

Preliminary studies:
not applicable
Main ADME resultsopen allclose all
Type:
absorption
Results:
maximum plasma levels after ingestion within 1 h, Gastrointestinal uptake factor: 1.2 (in healthy population).
Type:
distribution
Results:
Speciation in blood: 80% bound to transferrin at 1 h. Volume of distribution: 10 L (equal to extracellular fluid)

Toxicokinetic / pharmacokinetic studies

Details on absorption:
About 1.2 % of ingested 26Al was absorbed. Absorption was highly affected by excess of citrate, nosological entities, added silicate.
Details on distribution in tissues:
80% of absorbed 26Al bound to transferrin at 1 h. Volume of distribution: 10 L (equal to extracellular fluid)
Details on excretion:
Rapid urinary excretion (80% of dose excreted in 10 days). Whole body measurements show retention of 4% of dose with residual half-life more than 6 years

Metabolite characterisation studies

Metabolites identified:
no
Details on metabolites:
not applicable, no metabolites were identified

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study results About 1.2 % of ingested 26Al was absorbed and absorption was highly affected by a variety of parameters. l elimination is characterized by a rapid phase of the most part of the dose and a slow phase of the remaining 4% of the dose.
Administration of 26Al orally or via injection is a reliable way of measuring kinetic parameters for Al via accelerator mass spectrometry. Experiments with either oral or injection administration of the isotope showed that about 1.2 % of ingested 26Al was absorbed and absorption was highly affected by a variety of parameters. Most of absorbed 26Al is bound to transferrin this is verified by the volume of distribution of Al which is equal to the volume of extracellular fluid. Al elimination is characterized by a rapid phase of the most part of the dose and a slow phase of the remaining 4% of the dose
Executive summary:

Administration of26Al orally or via injection is a reliable way of measuring kinetic parameters for Al via accelerator mass spectrometry. Experiments with either oral or injection administration of the isotope showed that about 1.2 % of ingested26Al was absorbed and absorption was highly affected by a variety of parameters. Most of absorbed26Al is bound to transferrin this is verified by the volume of distribution of Al which is equal to the volume of extracellular fluid. Al elimination is characterized by a rapid phase of the most part of the dose and a slow phase of the remaining 4% of the dose

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