Slags, ferronickel-manufg.

Basic toxicokinetics

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

Test material information

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 results

Main ADME results 1

Type:

absorption

Results:

maximum plasma levels after ingestion within 1 h, Gastrointestinal uptake factor: 1.2 (in healthy population).

Main ADME results 2

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