Phosphinic acid, aluminum salt (3:1)

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1986

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1986

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Absorption and distribution of aluminium following and intravenous + oral administration.

GLP compliance:

no

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

IUPAC Name:

aluminum trichloride

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

- Weight: 250-350 g.
- Housing: three per cage.
- Photoperiod: 12h light + 12 h dark cycle.

Administration / exposure

Route of administration:

other: intravenous dose followed by oral administration

Vehicle:

water

Details on exposure:

Intravenous dose followed by oral administration by gavage of a saline solution equivalent to 8.1 mg/kg Al.

Duration and frequency of treatment / exposure:

Two days: the intravenous dose was administered on Day 1 and the oral dose was administered on Day 2.

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

8.1 mg/kg bw/day (nominal)

Remarks:

oral dose

Doses / concentrations 2

Dose / conc.:

8.1 mg/kg bw/day (nominal)

Remarks:

intravenous dose

No. of animals per sex per dose / concentration:

Six animals per sex per dose

Control animals:

no

Details on dosing and sampling:

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 Na2EDTA solution and deionized distilled water. The vials containing blood samples were refrigerated until the time of assay.

Results and discussion

Main ADME results

Main ADME results 1

Type:

absorption

Results:

27% from oral

Main ADME results 2

Type:

distribution

Results:

plasma

Main ADME results 3

Type:

metabolism

Results:

none

Main ADME results 4

Type:

excretion

Results:

60 % in the urine and the remaining 40 % into feces.

Toxicokinetic / pharmacokinetic studies

Details on absorption:

The degree of aluminum absorption in animals depends on a number of parameters, including pH, aluminum speciation and dietary factors. More aluminum is absorbed at low pH than at neutral or high pH. Aluminum absorption does not appear to occur in the stomach, where most aluminum is converted to soluble monomolecular species at low pH. However, in the intestine, at near-neutral pH, most of the aluminum changes into insoluble form and is not available for uptake.
The small portion that remains available for transport is the fraction that has been complexed with organic molecules in the stomach, allowing it to remain soluble at the higher pH of the small intestine.
The composition of the food eaten in conjunction with drinking water that contains aluminum has a strong effect on the absorption of aluminum.

Details on distribution in tissues:

Once absorbed into the bloodstream, aluminum binds to certain plasma proteins, in particular albumin and transferrin. In the tissues, aluminum is nearly always found in association with iron.
The highest levels of aluminum in mammalian tissues are found in the skeleton, lungs, kidneys, spleen, thyroid and parathyroid glands. Experience with dialysis patients has shown that aluminum has the potential to accumulate in the skeleton and brain.

Toxicokinetic parameters

Toxicokinetic parameters 1

Test no.:

#1

Toxicokinetic parameters:

half-life 1st: 5.3

Remarks:

following intravenous dosing

Toxicokinetic parameters 2

Test no.:

#1

Toxicokinetic parameters:

half-life 1st: 4.9

Remarks:

following oral dosing

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

There is no metabolites.

Applicant's summary and conclusion

Conclusions:

Interpretation of results: low bioaccumulation potential based on study results.
The Aluminium fraction absorbed following intravenous and oral administration remains in the plasma bound to proteins, with no apparent penetration into organs or blood cells. Excretion occur in the urine. Non absorbed Al is excreted through the faeces.
No metabolism and no bioaccumulation is detected.

Executive summary:

The kinetics of aluminum were determined in the rat. Intravenous bolus and oral doses of 8.1-mg/kg of aluminum as the chloride salt were administered to six rats. Serial blood samples and total urine and feces were collected and assayed for aluminum by atomic absorption spectrophotometry. It was found that aluminum 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 feces. The half-life of aluminium in rat was 5.3 h (intravenous administration) and 4.9 h (oral administration).