Reaction mass of aluminium hydroxide and aluminium nitrate and aluminium sulphate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

6 Dec 2005 - 11 Jun 2006

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

GLP - Guideline study tested with the source substance CAS 1327-41-9. According to the ECHA guidance document “Practical guide 6: How to report read-across and categories (March 2010)”, the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance

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

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Aluminium chloride basic

IUPAC Name:

Aluminium chloride basic

Constituent 2

Reference substance name:

Aluminum chloride, basic

EC Number:

215-477-2

EC Name:

Aluminum chloride, basic

Cas Number:

1327-41-9

IUPAC Name:

aluminum trichloride

Details on test material:

- Name of test material (as cited in study report): aluminium chloride basic
- Substance type: aluminium salt
- Physical state: liquid (yellow)
- Analytical purity: not reported
- Composition of test material, percentage of components: confidential information
- Lot/batch No.: confidential information
- Expiration date of the lot/batch: confidential information
- Stability under test conditions: ctable
- Storage condition of test material: at room temperature in the dark

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: standard pelleted laboratory animal diet, ad libitum
- Water: tap-water, ad libitum
- 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:

unchanged (no vehicle)

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 = 0.55)

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:
0.450 g solution/kg bw (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.

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

Toxicokinetic / pharmacokinetic studies

Details on absorption:

The average oral absorption of aluminium was 0.028% for the males and 0.026% for the females after dosing aluminium chloride basic. This indicates that absorption is very low and more or less similar between the compounds.

Details on distribution in tissues:

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

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 (migrated information): other: 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 chloride basic was very low (0.028% in males, 0.026% in females).

Executive summary:

Absorption and excretion of aluminium chloride basic was tested in Wistar rats according to OECD guideline 417. The test substance was administered once in a dose level of 200 mg/kg AlCl3 (= 0.450 g of test solution/kg bw). The following parameters were evaluated: mortality, clinical signs, and 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 0.028% for males and 0.026% for females. This shows that absorption is very low.

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