Aluminum chloride, basic, reaction products with silica

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: This is not a guideline study so there is no standard against which it can be directly assessed. When compared to OECD 407 the investigation lacked clinicla pathology, behaviour and eye examination and had a very restricted tissue list.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1976

Report date:

1976

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Deviations:

not specified

GLP compliance:

no

Remarks:

Study preceded introduction of GLP

Limit test:

no

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:

- Name of test material: Saffil alumina fibre
- Substance type: White milled fibre
- Physical state: solid
- Analytical purity: assumed to be 100%
- Lot/batch No.: Bag 3
- Expiration date of the lot/batch: indefinitely stable
- Stability under test conditions: indefinitely stable
- Storage condition of test material: ambient

Test animals

Species:

rat

Strain:

other: Alpk/ AP (Wistar derived)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: bred at ICI CTL
- Age at study initiation: not specified
- Weight at study initiation: males 165- 174 g females 161- 164 g (inferred from data)
- Housing: Controls and tests Sub groups A suspended wire cages Sub groups B individual metabolism cages
- Diet: cubed powder 'O' incorporated into 2.5% w/v aqueous agar ad libitum
- Water : municipal drinking water ad libitum

ENVIRONMENTAL CONDITIONS :
not specified

IN-LIFE DATES:
not stated

Administration / exposure

Route of administration:

oral: feed

Vehicle:

other: 2.5% agar mixture with diet

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS:

DIET PREPARATION
- Rate of preparation of diet : not stated
- Mixing appropriate amounts with: cubed powder 'O' and 2.5 % agar
- Storage temperature of food: not stated

VEHICLE
- Justification for use and choice of vehicle : palatability study
- Concentration in vehicle: 2.5% and 10%

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

6 weeks

Frequency of treatment:

continuous

Doses / concentrations

Remarks:

Doses / Concentrations:
2.5 % and 10%
Basis:
nominal in diet

No. of animals per sex per dose:

2 per sex in control group, 3 per sex in test groups

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: Palatability
- Rationale for animal assignment (if not random): Not stated

Positive control:

None

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS:
- Time schedule: Daily

BODY WEIGHT: Measured weekly

FOOD CONSUMPTION AND COMPOUND INTAKE
- Food consumption for each animal in a metabolism cage was measured daily together with urine and faecal output

URINALYSIS: Aluminium content only
- Metabolism cages used for collection of urine: Yes
- Animals fasted: No

Sacrifice and pathology:

GROSS PATHOLOGY: Not studied
HISTOPATHOLOGY: Not studied

Statistics:

Analysis of variance

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

effects observed, treatment-related

Description (incidence and severity):

Aluminium in urine rose in proportion to dose ingested

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

not examined

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Details on results:

CLINICAL SIGNS AND MORTALITY: None

BODY WEIGHT AND WEIGHT GAIN: See table

FOOD CONSUMPTION: See table

Aluminium balance: see table

Effect levels

Dose descriptor:

NOAEL

Effect level:

> 4 000 mg/kg bw (total dose)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: overall effects mortality; body weight; food consumption

Remarks on result:

not determinable

Remarks:

no NOAEL identified

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Table 1 Body weight, Food intake and excretion

	Males			Females
	Control	2,5% SAFFIL	10% SAFFIL	Control	2,5% SAFFIL	10% SAFFIL
Dry matter intake (g/wk)	153.2	157.0	180.5	140.4	159.9	161.6
Dry matter intake of Oakes diet (g/wk)	145.7	144.9	154.7.	133.0	143.0	138.5
SAFFIL intake (g/wk)	0	4.0	17.2	0	4.0	15.4
Faeces weight (g/wk)	4205	49.0*	62.1**	36.1	42.4**	54.2**
Urine volume (ml/wk)	144.9	94.9*	126.1	128.6	134.4	168.7
Bodyweight at week 6 (g)	393	364	371	263	275	279
Wk 6 bodywt (% initial wt)	226.	220	222	163	168	171

*Significantly different from control at the 5% level

**Significantly different from control at the 1% level

 

Chemical analysis 

The aluminium balance is shown in Table 2. There was a small increase in urinary aluminium excretion but essentially all of the ingested aluminium is recovered in the faeces

 

The ingested aluminium was shown to be excreted rapidly when the subgroups ’b’ were fed control diet during week 7 when >90% of excess aluminium was recovered in the faeces within 24 hours

 

 Aluminium content of tissues was not significantly increased, except for the residual carcasses, where there was a significant increase at week 6 in rats fed 10% SAFFIL in the diet. The difference was no longer significant at week 7 after 1 week on control agar diet.

 

 

Table 2 Aluminium balance (mg Al /week )

	Control	2.5% SAFFIL	!0% SAFFIL
Males
Mean intake	25 +/-5	1935 +/-112	8079+/-313
Mean in faeces	38+/-3	2135 +/-80	8039 +/-409
Mean in Urine	0.052 +/-0.01	0.16 +/-0.047	0.245 +/-0.025
Mean balance	150%	110%	101%
Females
Mean intake	23 +/-5	1912+/-31	7231 +/-188
Mean in faeces	28 +/-13	1915 +/-47	6980 +/-193
Mean in Urine	0.098+/-0.039	0.249 +/-0.041	0.496 +/-0.077
Mean balance	122%	100%	97%

 

Applicant's summary and conclusion

Conclusions:

Administration of the test substance in diet at the highest level that could be incorporated corresponded to a daily intake in excess of 6 g/ kg / day. The lower dose was considered to be the maximum that could be used for long term studies. The aluminium retention by the rats was minimal, urinary excretion of aluminium corresponded to about 50% of that which can be extracted in 5 % acetic acid.
It was concluded that the LD50 for Saffil fibres was not less than that for calcined alumina and in excess of 4g/kg.

Executive summary:

This study did not raise any concerns on the oral toxicity of the test article. The lack of absorption indicates that no further activity is to be expected.