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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics
Type of information:
experimental study
Adequacy of study:
key study
Study period:
06 December 2005 - 11 June 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study was conducted according to OECD 417 and under GLP conditions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report date:
2007

Materials and methods

Objective of study:
absorption
excretion
Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 417 (Toxicokinetics)
Deviations:
no
Principles of method if other than guideline:
Not relevant
GLP compliance:
yes

Test material

Constituent 1
Test material form:
solid: granular
Remarks:
white crystalline granules
Details on test material:
- Name of test material (as cited in study report): Aluminium Sulphate
- Molecular formula: Al2(SO4)3, 14.5 H2O
- Molecular weight: 603,36
CAS Number: 16828-12-9 or 10043-01-3
- Substance type: Aluminium salt
- Physical state: Solid
- Storage condition of test material: At room temperature in the dark
Specific details on test material used for the study:
- Stability under test conditions: Stable for at least 48 hours
Radiolabelling:
no

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: Approx. 9 weeks
- Weight at study initiation: Within 20% of the sex mean (OECD 417)
- Fasting period before study: Approx. 18h prior to and for approx. 4h after dose administration (water ad libitum)
- Housing: Individually
- Individual metabolism cages: yes
- Diet (e.g. ad libitum): Ad libitum, standard pelleted laboratory animal diet
- Water (e.g. ad libitum): Ad libitum, tap-water
- Acclimation period: At least 5 days before study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.6-22.0
- Humidity (%): 23-63
- Air changes (per hr): Approx. 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:
Test substance was homogenised to a visually acceptable level. No adjustment was made for specific gravity of the test substance. pH value of the ready to use solution was measured (pH value = 3.34)

HOMOGENEITY AND STABILITY OF TEST MATERIAL:
Formulation analysis was performed and reported.
Duration and frequency of treatment / exposure:
Single dose
Doses / concentrations
Remarks:
Doses / Concentrations:
0447 mg (Al content equimolar to 200 mg/kg AlCl3)
No. of animals per sex per dose / concentration:
4
Control animals:
no
Positive control reference chemical:
Not relevant
Details on study design:
- Dose selection rationale: Dose level should be high enough to ensure measurable differences in absorption and excretion between the three components without doing physical harm to the test animals. The highest level tested in a subchronic test was 1600 mg/l aluminium chloride in drinking water (around 180 mg/kg/day). At that dose level, measurable differences in a neurobehavioural test battery were found, but no signs of distress or any clinical observable adverse effects (Zheng & Liang, 1998). In a short-term study, no adverse effects were expected of a slightly higher dose. Aluminium chloride is generally considered to be the most easily absorbed aluminium salt, therefore the others were expected to have no adverse effects either.
- Rationale for animal assignment (if not random): Random
Details on dosing and sampling:
PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: urine, faeces
- Time and frequency of sampling: Predose and at 24-hours intervals after dosing until 120 hours.

Concentration data of aluminium obtained after dosing were corrected for the predose sample (outside sources)

Absorption:
Only urinary data was taken into account for calculating the oral absorption of aluminium. The animals in which the predose concentration was zero (below the LOQ) in the urine were not taken into account in calculating the percentage of absorption.

Urine and faeces analysis by ICP-MS
Statistics:
Mean and standard deviation were appropriate

Results and discussion

Preliminary studies:
Not relevant

Toxicokinetic / pharmacokinetic studies

Details on absorption:
The average oral absorption of aluminium was 0.037% for the males and 0.001% for the females after dosing Aluminium chloride basic. This indicates that absorption is very low and more or less similar between the compounds. There seems to be a gender difference in the absorption of Aluminium Sulphate, with the males having the higher absorption.
Details on distribution in tissues:
Not relevant
Details on excretion:
Urine:
The excretion of aluminium in urine was very low, <0.5% for all three compounds and both sexes. Excretion occurred mainly in the first 24 hours after dosing.

Faeces:
Significant aluminium concentrations were present predose. Most of the aluminium was excreted in the faeces (corrected for predose sample), probably indicating that aluminum is not absorbed after oral administration. In general, excretion took place during the first 24 hours after dosing. In some cases, the percentage of aluminium excreted was >100% (outside sources).

Metabolite characterisation studies

Metabolites identified:
no
Details on metabolites:
Not relevant

Any other information on results incl. tables

Baseline aluminium concentration

A significant difference in predose aluminium concentrations was shown for the different animals. For some animals significant aluminium concentrations were present predose, while for other animals these concentrations were below the LOQ. This indicates that aluminium exposure can also occur from external sources, outside dosing alone. Therefore, concentration data of aluminium obtained after dosing were corrected for the predose sample (outside sources).

Observations

- No mortality was observed in the study

- No clinical signs were observed

- Body weights at day of treatment were within 20% of the mean sex body weight.

Applicant's summary and conclusion

Conclusions:
Interpretation of results: very low oral absorption
This toxicokinetic study (OECD 417) in Wistar rats revealed that oral absorption of 200 mg/kg bw AlCl3 molar equivalents Aluminium Sulphate was very low (0.037% in males, 0.001% in females). A gender difference in the absorption of test article was observed, with the males having the higher absorption.
Executive summary:

Absorption and excretion of Aluminium Sulphate was tested in the Wistar rat based on OECD guideline 417. The test substance was administered once in a dose level of 200 mg/kg AlCl3 (= 445 mg of test article). The following parameters were evaluated: Mortality, clinical signs, body weights. Urine and faeces were collected and weighed at predose and at 24 hours intervals after dosing until 120 hours.

No mortality was observed in the study. No treatment related findings were noted.

Significant aluminium concentrations were present predose, in urine as well as faecal samples (although predose concentrations were very variable for the urine data). This indicates that aluminium exposure can also occur from external sources, outside dosing alone. Therefore, concentration data of aluminium obtained after dosing were corrected for the predose sample.

The excretion of aluminium in urine was very low, <0.5% in both sexes. Excretion occurred mainly in the first 24 hours after dosing. Most of the aluminium was excreted in the faeces, indicating that aluminium is not absorbed after oral administration. In general, excretion took place during the first 24 hours after dosing. In some cases, the percentage of aluminium excreted in faeces was >100%. This is due to the fact that animals can also be exposed to aluminium from outside sources.

The average oral absorption was 0.037% for males and 0.001% for females. This indicates that absorption is very low . There seems to be a gender difference in the absorption of Aluminium Sulphate, with the males having the higher absorption.

This toxicokinetic study revealed that oral absorption of 200 mg/kg bw AlCl3 molar equivalents Aluminium sulphate was very low.