Aluminium sulphate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Reliable without restrictions.Well-presented study, with relevant measurement of chemical concentrations

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Materials and methods

Objective of study:

excretion

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPPTS 870.8500 (Toxicokinetic Test)

Principles of method if other than guideline:

Method other:
Calculation of the filtered load of aluminum which was obtained from measurements of the filter ability of aluminum from the plasma and the glomerular filtration rate.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Aluminium sulphate

EC Number:

233-135-0

EC Name:

Aluminium sulphate

Cas Number:

10043-01-3

Molecular formula:

Al.3/2H2O4S; General formula Al2(OH)x(SO4)(3-x/2), with x=0 and x=3 and x ranging from 0 to 3.

IUPAC Name:

Aluminium sulphate

Details on test material:

up to 800 micrograms of aluminum-sulfate (10043013) or aluminum-citrate (31142560)

Radiolabelling:

not specified

Test animals

Species:

rat

Strain:

not specified

Sex:

not specified

Administration / exposure

Route of administration:

intravenous

Vehicle:

other: intravenously

Duration and frequency of treatment / exposure:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
25 micrograms to 800 micrograms of aluminum-sulfate (10043013) or aluminum-citrate (31142560)

Control animals:

yes

Positive control reference chemical:

no

Details on study design:

Aluminum reabsorption by the kidney of rats treated with up to 800 micrograms of aluminum-sulfate (10043013) or aluminum-citrate (31142560) was determined by calculation of the filtered load of aluminum which was obtained from measurements of the filter ability of aluminum from the plasma and the glomerular filtration rate. The excretion of aluminum-citrate was found to be markedly higher than that of aluminum-sulfate. A decrease in the percentage of ultrafilterable aluminum was seen with increasing plasma aluminum concentrations.
The percentage of ultrafilterable aluminum-citrate was considerably higher than that seen for aluminum-sulfate over the range of plasma aluminum concentrations.
The excretion of aluminum-citrate, however, for any given filtered load, was not significantly different from the excretion of aluminum-sulfate.

Results and discussion

Preliminary studies:

Aluminum reabsorption by the kidney of rats treated with up to 800 micrograms of aluminum-sulfate (10043013) or aluminum-citrate (31142560) was determined by calculation of the filtered load of aluminum which was obtained from measurements of the filter ability of aluminum from the plasma and the glomerular filtration rate. The excretion of aluminum-citrate was found to be markedly higher than that of aluminum-sulfate. A decrease in the percentage of ultrafilterable aluminum was seen with increasing plasma aluminum concentrations. The percentage of ultrafilterable aluminum-citrate was considerably higher than that seen for aluminum-sulfate over the range of plasma aluminum concentrations. The excretion of aluminum-citrate, however, for any given filtered load, was not significantly different from the excretion of aluminum-sulfate.

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Aluminum reabsorption by the kidney of rats treated with up to 800 micrograms of aluminum-sulfate (10043013) or aluminum-citrate (31142560)

Details on distribution in tissues:

kidney, blood

Transfer into organs

Test no.:

#1

Transfer type:

blood/placenta barrier

Observation:

distinct transfer

Remarks:

aluminium excretion by exploiting the normal renal handling of aluminium.

Details on excretion:

The excretion of aluminum-citrate was found to be markedly higher than that of aluminum-sulfate. A decrease in the percentage of ultrafilterable aluminum was seen with increasing plasma aluminum concentrations. The percentage of ultrafilterable aluminum-citrate was considerably higher than that seen for aluminum-sulfate over the range of plasma aluminum concentrations. The excretion of aluminum-citrate, however, for any given filtered load, was not significantly different from the excretion of aluminum-sulfate.

Toxicokinetic parameters

Test no.:

#1

Toxicokinetic parameters:

half-life 1st: 2 h

Metabolite characterisation studies

Metabolites identified:

not measured

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results aluminum-sulfate exposure may be a form of aluminum-citrate which is then easily reabsorbed and that aluminum removal by the body may be enhanced by preventing the tubular reabsorption of this easily filtered aluminum species.
The authors conclude that the aluminum filtered following aluminum-sulfate exposure may be a form of aluminum-citrate which is then easily reabsorbed and that aluminum removal by the body may be enhanced by preventing the tubular reabsorption of this easily filtered aluminum species.

Executive summary:

The known toxicity of aluminium, and the toxicity of agents (such as desferrioxamine) used to remove aluminium from the body, has prompted us to investigate whether there may be ways of enhancing aluminium excretion by exploiting the normal renal handling of aluminium.

Aluminium (as sulphate or citrate) was administered intravenously to conscious rats at doses ranging from 25 micrograms (0.93 mumol) to 800 micrograms (29.6 mumol) aluminium, and aluminium excretion was monitored over the following 2 h.

 Measurements of the filterability of aluminium from the rat plasma, and the glomerular filtration rate (inulin clearance), enabled us to calculate the filtered load of aluminium, and hence determine aluminium reabsorption.

 At all doses of administered aluminium, that administered as sulphate was excreted less effectively than that administered as citrate.

This difference was attributable to the much greater filterability of aluminium administered as citrate. However, for any given filtered load, the excretion of aluminium administered as citrate was not significantly different (in either fractional or absolute terms) from the excretion of aluminium administered as sulphate.

 It seems likely that, following aluminium sulphate administration, the filtered aluminium may be an aluminium citrate form which is then reabsorbed in the same way as aluminium administered as citrate. It is thus apparent that aluminium removal from the body could be further enhanced if it were possible to prevent the tubular reabsorption of the aluminium species which is so effectively filtered following aluminium citrate administration.