Aluminium chloride

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: basic information given

Data source

Reference

Reference Type:

publication

Title:

Absorption and Disposition of Aluminium in the Rat.

Author:

Gupta, S.K., Waters, D.H., Gwil, P.R.

Year:

1986

Bibliographic source:

J. Pharmaceutical Sciences 75, 5, 586 - 589

Materials and methods

Objective of study:

toxicokinetics

Principles of method if other than guideline:

Kinetic analyses of aluminium in the rat following intravenous and oral doses of aluminium chloride.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Aluminium chloride

EC Number:

231-208-1

EC Name:

Aluminium chloride

Cas Number:

7446-70-0

Molecular formula:

AlCl3

IUPAC Name:

trichloroalumane

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

The rats (weighing 250 - 350 g) were exposed to a 12-h light: 12-h dark cycle and were housed three per cage. The average aluminium content of food and water was determined to be 0.1 mg/E; and 3 μg/10 mL, respectively. A chronic indwelling catheter was placed in the right jugular vein under light ether anesthesia. Animals were allowed to recover at least 4 8 h following surgery.

Administration / exposure

Route of administration:

other: i.v. and oral

Details on exposure:

Six rats received intravenous doses of aluminium chloride, and then oral doses following a two-week washout period.
The dose equivalent to 8.1 mg/kg elemental aluminium was prepared by dissolving 1.45 g of AlCl3 x 6H20, which is equivalent to 162.0 mg of elemental aluminium, in enough saline to give 10 mL of solution. Following light ether anesthesia, 0.5 mL/kg of the aluminium chloride solution was infused into the dorsal tail vein at a rate of 1 mI/min. Following an overnight fast, the oral dose of aluminium chloride was administered by intubation. Six additional rats were given an identical intravenous dose. Urine and feces were collected for 4 d following dose administration and blood was sampled for 10 h.
Sample Collection: Treated rats were placed in plastic metabolism cages and blood samples (0.1 mL) were drawn at 0, 5, 10, 15, and 30 min and 1, 2, 3, 4, 5, 6, 8, and 10 h following intravenous administration, and at 0, 15, and 30 min and 1, 2, 3, 4 , 5, 6, 8, and 10 h following oral administration. Urine and feces were collected for 4 d and refrigerated until time of assay.
Blood samples were collected in heparinized glass scintillation vials, which had been sequentially acid-washed, and rinsed with a Na2-EDTA solution and deionized distilled water. The vials containing blood samples were refrigerated until the time of assay.
Analytical Procedure: All aluminium standards were prepared by dissolving 8.95 mg AlCl3 x 6H20 in water to make 1 L of solution and using this stock solution to produce final aluminium concentrations of 0, 0.02, 0.04, 0 .06, 0.08 , and 0.1 μg/mL in samples of 0.1-mL control blood, 0.1-mL control urine, or 0.1-g control feces.
Analyses were performed using an atomic absorption spectrophotometer with a hollow cathode lamp as the light source. Measurements were recorded. Both standards and samples were assayed in triplicate.
Base-line correction: On the day prior to each treatment, five 0.1-mL blood samples were drawn periodically from each rat to determine background aluminum concentrations. These values were used for the base-line correction. The base-line correction for aluminum in urine and feces was made in a similar manner. Urine and fecal matter for each rat was collected over a 24-h period prior to aluminum chloride administration. The average aluminum concentration in the urine and feces was calculated from the pooled 24-h samples. This value was then subtracted from the concentration of aluminum in each urine and fecal sample obtained following aluminum chloride administration .
Blood and Plasma Protein Binding Studie: A small volume of a concentrated aluminium chloride solution was added to 6 mL of heparinized whole rat blood to produce blood concentrations of 110, 220, and 440 ug/mL, which were equivalent to aluminium concentrations in the blood immediately following intravenous bolus administration. The cells were assayed for aluminium, and protein binding studies were performed on plasma, using ultrafiltration.
Kinetic Analysis: Individual blood aluminium concentration-time data were analyzed using both compartmental and noncompartmental methods. For the compartmental analysis, initial estimates of the parameters and compartmental configuration were evaluated.

Doses / concentrations

Remarks:

Doses / Concentrations:
Intravenous bolus and oral doses of 8.1 mg/kg of aluminium as the chloride salt.

No. of animals per sex per dose / concentration:

6

Results and discussion

Toxicokinetic / pharmacokinetic studies

Toxicokinetic parameters

Toxicokinetic parameters:

other: Aluminium did not significantly penetrate the cellular components of blood.

Applicant's summary and conclusion

Conclusions:

It was found that aluminium did not significantly penetrate the cellular components of blood. Plasma protein binding was determined to be about 98%. Sixty percent of the intravenous dose was excreted in the urine and the remaining 40% was excreted in the faeces.