Aluminium tributanolate

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:

test procedure in accordance with national standard methods with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1984

Materials and methods

Objective of study:

distribution

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Male Sprague-Dawley rats were treated daily by gastric intubation (6 days/wk) with 100 mg aluminium/kg body weight in the form of aluminium hydroxide (9 wk) or with tap-water (control, 9 wk). Young adult and aged Wistar rats were treated with 100 mg aluminium/kg body weight as aluminium hydroxide or with carboxymethylcellulose (vehicle controls). The cerebral cortex, hippocampus, cerebellum and samples of bone from each rat were analysed for aluminium, after digestion with nitric acid, using graphite furnace atomic absorption spectroscopy.

Test material

Test material information

Constituent 1

Reference substance name:

Aluminium hydroxide

EC Number:

244-492-7

EC Name:

Aluminium hydroxide

Cas Number:

21645-51-2

Molecular formula:

AlH3O3

IUPAC Name:

aluminum trihydroxide

Radiolabelling:

no

Test animals

Species:

rat

Strain:

other: Sprague-Dawley and Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: male Sprague Dawley from Anticimes Solantuna Sweden, male and female Wistar rats from Möllegaard Ejby Denmark
- Age at study initiation: young no data; aged 2 years
- Weight at study initiation: young males 140 g, females 300 g; aged no data
- Housing: no data
- Diet standard pellet diet (Astra Ewos, Södertälj Sweden) ad libitum
- Water: tap water ad libitum

ENVIRONMENTAL CONDITIONS: no data

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Duration and frequency of treatment / exposure:

young rats: 9 weeks, daily, 6 days/week
aged rats: 4 weeks, daily, 6 days/week

Doses / concentrations

Dose / conc.:

100 mg/kg bw/day (nominal)

Remarks:

as Al

No. of animals per sex per dose / concentration:

8 males Sprague Dawley for controls and 9 male Sprague Dawly at 100 mg/kg bw
No data on Wistar rats

Control animals:

yes, concurrent vehicle

Statistics:

Kruskal-Wallis, Mann-Whitney U-test, student t-test

Results and discussion

Main ADME results

Type:

distribution

Results:

no increases of aluminium concentration compared to control was found in the brain or the bone. No difference was established between young and aged rats

Metabolite characterisation studies

Metabolites identified:

no

Any other information on results incl. tables

No accumulation of aluminium was seen.

Sprague Dawley	Average concentration aluminium in µg/g wet weight
	cortex	hippocampus	cerebellum	bone
controls	0.0013	0.0014	0.0022	0.355
Al(OH)3	0.0013	0.0014	0.0011	0.410

 

Applicant's summary and conclusion

Conclusions:

No accumulation of aluminium in the brain or bones is seen in rats treated with Al(OH)3 for 9 weeks. No difference was observed between aged and young rats

Executive summary:

Male Sprague-Dawley rats were treated daily by gastric intubation (6 days/wk) with 100 mg aluminium/kg body weight in the form of aluminium hydroxide (9 wk) or with tap-water (control, 9 wk). Young adult and aged Wistar rats were treated with 100 mg aluminium/kg body weight as aluminium hydroxide or with carboxymethylcellulose (vehicle controls). The cerebral cortex, hippocampus, cerebellum and samples of bone from each rat were analysed for aluminium, after digestion with nitric acid, using graphite furnace atomic absorption spectroscopy. The mean aluminium concentrations detected in the control Sprague-Dawley rats were 0.013-0.022 microgram/g wet weight in the various brain regions and 0.355 microgram/g in the bone. No significant increase in tissue aluminium concentrations was observed in Sprague-Dawley or Wistar rats after treatment with aluminium hydroxide.