Aluminum chloride, basic, reaction products with silica

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

12/1974 - 10/1977

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study preceded guidelines and GLP but was audited at ICI to standards equivalent to GLP. Compared to OECD 453 this study lacked clinical pathology in the context of information available from other studies any deficiencies do not materially limit the utility of this study.

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Objective of study:

distribution

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: OECD 453

Deviations:

not applicable

Principles of method if other than guideline:

Feeding study not primarily for toxicokinetic purposes but distribution of fibres was extensively studied.

GLP compliance:

no

Remarks:

study preceded introduction of GLP

Test material

Test material information

Constituent 1

Reference substance name:

oxo[(oxoalumanyl)oxy]alumane

EC Number:

614-074-2

Cas Number:

675106-31-7

Molecular formula:

UVCB

IUPAC Name:

oxo[(oxoalumanyl)oxy]alumane

Details on test material:

2 batches ASK619-625 , ASK627-632 milled, median diameter by TEM was 2.05 microns and length 18 microns, purity assumed to be 100%

Radiolabelling:

no

Test animals

Species:

rat

Strain:

other: Alpk/AP Wistar derived

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Source: Bred at ICI CTL
- Age at study initiation: 8 weeks at delivery
- Weight at study initiation: Males: 200g +/- 20% , female: 185g +/-20%
- Housing: per cage in suspended wire cages
- Individual metabolism cages: no
- Diet cubed powder 'O' incorporated into 2.5% w/v aqueous agar, ad libitum
- Water : municipal drinking water ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 oC +/- 2 oC
- Humidity (%): not controlled
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 hours light , 12 hours dark.

IN-LIFE DATES: From: December 1974 To: October 1977

Administration / exposure

Route of administration:

oral: feed

Vehicle:

other: agar gel

Details on exposure:

Groups of 64 rats per sex given diet as follows:

Group 1 control agar diet
Group 4 experimental fibre at 0.025 % in diet w/w
Group 5 experimental fibre at 0.25 % in diet w/w
Group 6 experimental fibre at 2.5 % in diet w/w

Duration and frequency of treatment / exposure:

All rats exposed for 2 years or after 70% overall mortality

Doses / concentrations

Remarks:

Doses / Concentrations:
Group 1 control agar diet
Group 4 experimental fibre at 0.025 % in diet w/w
Group 5 experimental fibre at 0.25 % in diet w/w
Group 6 experimental fibre at 2.5 % in diet w/w

No. of animals per sex per dose / concentration:

64

Control animals:

yes, concurrent vehicle

Positive control reference chemical:

UICC chrysotile asbestos at 0.025 and 1.25 %

Details on study design:

- Dose selection rationale:
Following a short preliminary study the highest concentration of alumina fibre was selected so that the received dose was more than 1g/kg
This dose did not meet the normal criteria for maximum tolerated dose in that there were only minor effects on body weight

Details on dosing and sampling:

Lungs, livers, alimentary canal and remaining carcass were examined for fibre and aluminium contents.

Statistics:

Data from males and females were analysed separately. For body weights, food consumption, tissue analysis and alumina fibre in ashed residues were compared to the control values using Student's t test (2 sided). Organ weights were examined by analysis of variance and covariance of body weight. Tumour incidence : Fisher's exact test. Mortality was analysed using the NCI programme were appropriate a test for trend was included.

Results and discussion

Main ADME results

Type:

other: absorption and distribution cannot be distinguished.

Results:

absorption and distribution cannot be distinguished.: Fibres measured as fibres or as aluminium, largely remained in the alimentary canal. This is complicated by the difficulty of measuring aluminium in biological material.

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Not quantified

Details on distribution in tissues:

See table below

Transfer into organs

Test no.:

#1

Transfer type:

other: Unknown

Observation:

other: elemental and fibre analysis

Details on excretion:

Not measured

Metabolite characterisation studies

Metabolites identified:

no

Details on metabolites:

This material is not metabolised, aluminium found outside the gut is of an unknown speciation.

Any other information on results incl. tables

Distribution of Aluminium in some organs after feeding on alumina fibres

		control	0.025% alumina fibre	0.25% alumina fibre	2.5% alumina fibre
Lungs (mg Al/organ)	Mean S D	2.97 3.73	3.94 1.77	3.08* 1.22	3.70* 1.91
Lungs (mg Al/organ (excluding 2 outliers)	Mean S D	1.69 1.04	3.36** 0.69
LiversµgAl /organ Males (excluding outliers)	Mean S D	38.9 34.2	36.8 29.9	22.2 7.3	15.3 9.0
LiversµgAl /organ Females (excluding outlier)	Mean S D	12.7 4.2	67.5 56.2	62.2 33.4	53.3 61.7
Aluminium in carcass (µgAl/g wet weight), sexes combined	Mean S D	13.5 23.5	9.2 11.5	9.7 12.9	9.6 14.8
Fibres in Alimentary tract (total) Males	Mean S D	119 109	167 71	97 33	237 73
Fibres in Alimentary tract (total) Females	Mean S D	292 337	393 353	432 168	132 126

* Significantly different at 5% level

**Significantly different at 1% level

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): low bioaccumulation potential based on study results
Ther was no evidence of systemic toxicity resulting from administration of the fibre and no evidence that the material penetrated the gastrointestinal tract in fibrous form. Aluminium could be absorbed in small quantities but did not accumulate in the organs or carcass on prolonged administration.

Executive summary:

There was a very small accumulation of aluminium of dubious statistical significance in the lungs of animals fed alumina fibre.