Aluminium fluoride

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2006

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:

2006

Report date:

2006

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Limit test:

no

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): aluminum trifluoride (CAS # 07784-18-1)
- Physical state: solid
- Analytical purity: 90%
- Lot/batch No.: reported as July 2004 (date of production)
- Stability under test conditions: until 31-12-2008
- Storage condition of test material: ambient temperature

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: 6 weeks old
- Weight at study initiation: not reported
- Fasting period before study: none
- Housing: in conventional conditions in macrolon cages with a bedding of wood shavings, 5 rats/cage, separated by sex
- Diet (e.g. ad libitum): commercial rodent diet (Rat and Mouse No. 3 breeding diet RM3) available ad libitum
- Water (e.g. ad libitum): tap water ad libium
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/- 3
- Humidity (%): 70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure:

nose only

Vehicle:

other: no data

Remarks on MMAD:

MMAD / GSD: MMAD were 1.2, 1.6, and 1.7 micrometers for the low, mid and high dose, respectively. The GSD were 3.7, 3.1, and 3.7 for the low, mid and high dose, respectively.

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: each unit consisted of a cylindrical column, surrounded by a transparent cylinder. The column had a volume of 50 L and consisted of a top assembly with the inlet of the test atmosphere, a rodent tube section and at the bottom, the base assembly with the exhaust port.
- Method of holding animals in test chamber: each rodent tube had 20 ports for animal exposure and the animals were secured in plastic animal holders
- Temperature, humidity, pressure in air chamber: The temperature and relative humidity of the test atmospheres were measured with an RH/T device



VEHICLE (if applicable)
-Not applicable

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

The empty ports in the unit were used for measurements of concentrations.

Duration of treatment / exposure:

28 days

Frequency of treatment:

6 hours/day for 5 days/week

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 1, 7, and 50 mg/m3
Basis:
analytical conc.

No. of animals per sex per dose:

5 sex/dose

Control animals:

yes, sham-exposed

Details on study design:

- Dose selection rationale: based on preliminary study
- Rationale for animal assignment (if not random): random

Positive control:

none

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: maximum 3 times on weekdays and once/day on weekends

DETAILED CLINICAL OBSERVATIONS: No

BODY WEIGHT: Yes
- Time schedule for examinations: once during acclimation period, one day before exposure period, at initaion of treatment, weekly thereafter, and once before sacrifice

FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes


FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Yes

WATER CONSUMPTION: No

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Time schedule for collection of blood: at necropsy
- Anaesthetic used for blood collection: Yes; nembutal
- Animals fasted: Yes
- How many animals: all

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at necropsy
- Animals fasted: Yes
- How many animals: all

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Other examinations:

None

Statistics:

One way ANOVA with Dunnets multiple comparison tests. Kruskal-Wallis non-parametric ANOVA followed by Mann-Whitney U tests.

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:

no effects observed

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

effects observed, treatment-related

Clinical biochemistry findings:

effects observed, treatment-related

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

not examined

Details on results:

HAEMATOLOGY
-Red blood cell concentration was significantly increased in females of the mid concentration group, which was not considered to be related to treatment. In males, the concentration of neutrophils was significantly increased in the high-dose group.

CLINICAL CHEMISTRY
-The albumin/globulin ratio in plasma was significantly decreased in male animals in the high concentration group, not considered to be related to treatment.

ORGAN WEIGHTS
- Increase in absolute and relative lung weights of males and females in the high dose group. Increase in absolute and relative liver weight in high dose males. Increase in absolute and relative heart weight of mid dose males, which was not considered to be related to treatment.

HISTOPATHOLOGY: NON-NEOPLASTIC
- Changes in lungs of all animals and in tracheobronchial lymph nodes of males and females in the high-concentration group. In lungs of high dose animals, multifocal alveolar pigment macrophages with particulate material in their cytoplasm was accompanied by inflammatory changes.

Effect levels

Dose descriptor:

NOAEL

Effect level:

7 mg/m³ air (analytical)

Sex:

male/female

Basis for effect level:

other: Significant changes in organ weights and histopathological changes in the lungs of high dose animals.

Target system / organ toxicity

Critical effects observed:

not specified