Aluminium fluoride

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented, according to accepted guidelines

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

- reliability scoring based on 1981 guideline

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Version / remarks:

- 1998

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: EEC (Annex II, point 5.2.3)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: J-MAFF test guidelines for acute inhalation studies

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Aluminium fluoride

EC Number:

232-051-1

EC Name:

Aluminium fluoride

Cas Number:

7784-18-1

Molecular formula:

AlF3

IUPAC Name:

aluminum trifluoride

Details on test material:

- Name of test material (as cited in study report): ALF3, Aluminium fluoride
- Physical state: dry solid, white powder
- Analytical purity: not reported
- Lot/batch No.: XP01_00008_01
- Expiration date of the lot/batch: not reported; however, the authors assumed stable for the duration of the study
- Storage condition of test material: in the dark at room temperature, 20°C, and in the original container

Test animals

Species:

rat

Strain:

other: Sprague-Dawley Crl: CD® (SD) IGS BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK Limited, Manston Road, Margate, Kent, England
- Age at study initiation: approximately 9-10 weeks
- Weight at study initiation: mean body weights of 284-293 g for males and 220-236 g for females
- Fasting period before study: not reported
- Housing: by sex, in groups of 5 per cage (stainless steel and wire mesh) suspended on a movable rack
- Diet (e.g. ad libitum): SDS rat and mouse diet (RM1 (E) SQC expanded pellet), ad libitum
- Water (e.g. ad libitum): tap water supplied by Anglian Water, ad libitum
- Acclimation period: 12 days, except 3 days for 2 replacement animals


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17.5-21.0°C
- Humidity (%): 30-62%
- Air changes (per hr): 15 per hr
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs light

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

EXPOSURE SYSTEM

Dust generator: A turntable dust generator was used to produce the test atmospheres containing the dust of AlF3. The test substance flowed from the hopper, assisted by agitation, into a concentric groove milled into the turntable. As the turntable rotated, the dust passed under the air ejector and was aspirated into the chamber air supply.

Exposure chambers: The snout-only exposure chambers used for the exposures were of cylindrical form (30 cm internal diameter, 45 cm height) and made of aluminium alloy. The internal surfaces of the chamber have a conformal chemically resistant coating. The chambers have an enclosed volume of approximately 30 litres. The rats were held for exposure in moulded polycarbonate restraining tubes which were attached at evenly spaced ports in the cylindrical section of the chamber, and were designed to allow only the snout to project into the chamber. Each rat was restrained in a forward position by an adjustable foamed plastic stopper which also provided a seal for the tube.

The test atmosphere entered through a port at the top centre of the chamber and passed out through a port at the base section below the level of the rats.

The exposure system was positioned inside a large cabinet equipped with an extract fan exhausting to atmosphere through an absolute filter.

Airflow balance: A soft rubber bag was incorporated downstream of the exposure chamber and, once partially inflated, served as a sensitive visual indicator of the balance between the passive test substance/air supply and exhaust airflows within the exposure system.

PROCEDURE

The test substance was used as supplied.

A supply of clean, dry air was connected to the generator and the supply pressure was adjusted to give a flow rate of 40 litres/minute, measured at the generator outlet. The passive test substance pick-up air flow was 12 litres/minute. An in-line flow meter was used to monitor the generator air supply throughout the exposure. The exhaust air flow was calibrated and adjusted to balance the chamber air supply.

The powder hopper was filled with AlF3 and attached to the generator. The turntable speed controller was set for an initial speed of 1.1 revolutions per minute (rpm) and was expected to generate a particulate aerosol at the maximum practicable concentration. The performance of the turntable generator with the test substance was assessed during preliminary generation trials. The rats to be exposed were placed into separate restraining tubes and the tubes were then attached to ports in the exposure chamber.

The turntable motor was switched on and the exposure was timed for 4 hours following a 2-minute equilibration period. The rotational speed of the turntable was adjusted on one occasion in order to increase the level of the maximun practicable concentration but was limited by the amount of test substance available.

Following the exposure period, the turntable was stopped and the exposure chamber was allowed to clear before the animals were removed for examination.

The rats were returned to the holding cages and food and water supplies were restored. The test rats were kept in a ventilated cabinet overnight and then returned to the holding room for the remainder of the observation period.

The control group was treated similarly but received clean air only for 4 hours. The control animals were returned to the holding room at the end of the exposure period.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

The time-weighted average chamber concentration was 0.530 mg/L and was considered to be the maximum practicable. The nominal concentration was 232.0 mg/L

No. of animals per sex per dose:

5 animals/sex in each the control and test group

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed intermittently for signs of reaction to the test substance during exposure and at least twice daily throughout the observation period; animals were weighed at least twice during the week prior to exposure, prior to exposure (Day 0) and weekly during the observation period, including the day of death.
- Necropsy of survivors performed: yes
- Other examinations performed: Clinical signs were recorded at the end of the chamber equilibration period, at 0.25, 0.5, and 1.0 hours, then at hourly intervals during the exposure. Clinical signs were recorded immediately following exposure and then at 1.0 and 2.0 hours post-exposure. During the observation period, clinical signs were recorded once in the morning and then as necessary following a later check for survival. A visual inspection of water bottles was conducted daily. The lungs (including the larynx and trachea) were removed, dissected clear of surrounding tissue, weighed, and the weights were recorded.

Results and discussion

Preliminary study:

Preliminary experimental work: The test substance, AlF3, was supplied as a dry solid, white powder. Attempts were made to pack a sample of the test substance into a Wright Dust Feed mechanism (WDF) canister, using a hydraulic bench press to assist packing, at a variety of pressures ranging from 0.1 to 3.0 tons. It was not possible to pack the test substance sufficiently to allow generation using a WDF. The test substance was then processed in order to produce a powder suitable for generating with a WDF. The processed test substance was still unsuitable for packing and in addition, one of the processing methods altered the colour of the test substance. It was considered that the test substance was not suitable for generation of a test aerosol using a WDF and the associated processing methods. A summary of test material preparation methods is presented in Table A (see attached file).

A turntable dust generator was used to produce the test atmosphere containing a particulate aerosol generated from the test substance, as supplied. The conditions used during Preliminary Generation Trial 2, summarized in Table B (see attached file) were selected, with the exception of the passive pick-up (12 litres/minute), for exposure of test rats to a particulate aerosol generated at the maximum practicable concentration.

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 0.53 mg/L air

Exp. duration:

4 h

Remarks on result:

other: 0.530 mg/L was considered the maximum practicable concentration

Mortality:

There were no unscheduled deaths.

Clinical signs:

other: Tables 1 and 3 (see attached files) summarize clinical signs observed during the exposure and observation period, respectively. During exposure: exaggerated breathing was evident in all test rats from 4 hours into exposure; soiling of the fur with excreta

Body weight:

There were no treatment-related effects on body weights.

Gross pathology:

There were no treatment-related findings at necropsy. Small dark foci were noted on the lungs of 2 males in the test group, 1 male in the control group, and 1 female in the test group.

Other findings:

A visual appraisal of the water bottles indicated that the amount of water consumed by test animals was similar to that of the control animals. There were no treatment-related effects on lung weights.

Any other information on results incl. tables

As Table 3 illustrates (see attached file), the mass median aerodynamic diameter (MMAD) of the test aerosol was 8.5 µm and approximately 42% of the particulates were considered of a respirable size (< 7 µm in aerodynamic diameter).

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: CLP (EC 1272/2008)