Cryolite, tripotassium

Specific investigations: other studies

Administrative data

Endpoint:

specific investigations: other studies

Remarks:

Respiratory irritation

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Protocol for the sensory irritation test in accordance with ASTM E981-84 and with respect to the housing etc. of the animals, according to the OECD Guideline for Testing of Chemicals no. 403, Acute inhalation toxicity, adopted 12 May 1981.

GLP compliance:

yes (incl. QA statement)

Type of method:

in vivo

Endpoint addressed:

respiratory irritation

Test material

Test material information

Constituent 1

Test material form:

solid: particulate/powder

Details on test material:

NOCOLOK 100 flux is a white crystalline powder and has the following characteristics:
Name of test material: NOCOLOK 100 flux
Batch number: 2701 (22 January 1998)
Contents:
K(28-31%)
Al (16-18%)
F (49-53%)
Ca (< 0.2%)
Fe (<0.03%)
Bulk density: 416 g/l
Melting point: 565°C
Storage conditions: room temperature

Test animals

Species:

mouse

Strain:

Swiss Webster

Sex:

male

Details on test animals or test system and environmental conditions:

The animals were individually housed under conventional conditions in macrolon cages with sterilized sawdust bedding. The number of air changes was about 10 per hour. A 12-hour light and 12-hour dark cycle was maintained. The temperature was between 20.0 and 23.5°C, relative humidity was between 47 and 70%.

During exposure the animals had no access to feed or water and were housed individually in the restrainers. Immediately after exposure, the animals were returned to their living cages and were kept there until necropsy seven days after exposure.

Administration / exposure

Route of administration:

inhalation: aerosol

Vehicle:

air

Details on exposure:

Animals were exposed to the test atmosphere in an experimental set-up. The animals were secured in modified plastic animal restrainers (Battelle) and placed individually in one of the four plethysmographs connected to a central exposure chamber. The animals were allowed to breath freely from a stream of fresh test atmosphere. Pressure transducers connected to the plethysmographs were sensing changes caused by in and expiration. A void filling was placed in each of the plethysmographs to reduce the chamber volume in order to increase signal strength. The electronically amplified signals were transmitted to a polygraph recorder for off-line manual calculations.
Sampling ports for the actual concentration, temperature and relative humidity measurements were located in the exhaust pipe, just above the central exposure chamber. The unit was illuminated externally by normal laboratory TL-lighting.

The inhalation equipment was designed to expose mice to a continuous supply of fresh test atmosphere. The test atmosphere was generated by delivering the test material using a dry material helix feeder to a jet mill (Institute's design), operated with dry pressurized air (less than 1% humidity). By means of an eductor, in fact used as a pump, a small fraction of the aerosol was withdrawn from the exhaust of the jet mill. Because the eductor withdrew the aerosol perpendicular to the main flow, the heavier particles could not make the turn and only smaller particles were selected for- the test atmosphere. The maximum attainable concentration was 600 mg/m3 with this setup.
The test atmosphere was passed to the inlet of the exposure unit. From there, the test atmosphere was directed towards the animal noses. At the outlet of the unit the test atmosphere was exhausted (see also Figure 1). The input pressures of the jet mill and the eductor were set at the desired levels (5.0, 2.0 and 2.0 bar for the mill, the jet and the eductor, respectively) at the beginning of the exposure period.

Particle size measurement: measurements were carried out using a 10-stage cascade impactor with a largest cut-off size of 32 pm. The Mass Median Aerodynamic Diameter (MMAD) and the mean geometric standard deviation (GSD) were calculated.

The mass median aerodynamic diameter of the particles was assessed twice, the results were 0.8 and 1.0 µm, respectively and the geometric standard deviations were 2.5 and 2.7, respectively.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

The concentration of the test material in the test atmosphere was determined one or two times during each exposure by gravimetric analysis.

Duration of treatment / exposure:

single exposure

Frequency of treatment:

20 or 30 minutes

Doses / concentrations

Remarks:

Doses / Concentrations:
283, 592 and 604 mg/m3
Basis:
analytical conc.

No. of animals per sex per dose:

4 males

Control animals:

yes

Details on study design:

Sensory irritation
Sensory (respiratory) irritation is a reflex mechanism of the trigeminal nerve and results in a decreased breathing frequency which, if low enough, is characterized by a post-inspiratory apnoea.
The groups were exposed by inhalation for a single 30-min period (for exposures A and B a 20-min period was accidentally used), after an acclimatization period of 10 minutes. A recovery period of 20 minutes in the animal restrainers was allowed after exposure.

The control respiratory rate was measured during the acclimatization period as the average of six ~20-sec periods recorded at 1-min intervals immediately preceding the exposure period. During the exposure period, the respiratory rate was measured for ~20-sec periods at 1-min intervals during the first six minutes of exposure and at 2-min intervals for the remainder of the exposure period. After exposure, rates were measured 5 times for ~20 sec at 1-min intervals, followed by 3-min intervals (after exposures A and B rates were measured 6 times for ~20 sec at 1-min intervals, followed by 2-min intervals). At the same time, changes in tidal volume were monitored by measuring the amplitude of the breathing signal. The response R, measured as the relative decrease in breathing rate, was calculated as follows:

R (during exposure): 1 - (exposure value/mean pre-exposure value)
R (after exposure): 1 - (recovery value/mean pre-exposure value).

Examinations

Examinations:

Behaviour, clinical signs and mortality
The mice were visually inspected just before exposure, for reactions to treatment during the exposure, shortly after exposure, and at least once daily during the observation period.

Body weights
Body weights were recorded just prior to exposure (day 0) and on days 1 and 7.

Necropsy
At the end of the 7-day observation period, all mice were killed by exsanguination from the abdominal aorta under ether anaesthesia. All mice were subsequently necropsied and examined for gross pathological changes. In addition, absolute and relative lung weights were determined.

Results and discussion

Details on results:

A decrease in breathing rate or post-inspiratory apnoea were not seen in the breathing pattern.

During exposure, no changes in behaviour were seen. No abnormalities were seen in clinical signs during the 7-day observation period. None of the mice died. Dose (exposure*time) related weight decrease was not observed. Abnormalities at necropsy consisted primarily of discoloured areas on the lungs to a varying extent in the highest concentration group.

From the results of the present study in mice, it was concluded that a sensory irritation response of inhalable particles of aluminium potassium fluoride at the technically highest attainable concentration under the conditions of this study (604 mg/m3) was not found.

Applicant's summary and conclusion

Conclusions:

Multiconstituent aluminium potassium fluoride does not induce sensory irritation in the respiratory tract.

Executive summary:

The airway irritating properties of multiconstituent aluminium potassium fluoride were studied in a GLP study by exposing three groups of four male mice to test atmospheres containing the substance at concentrations of 283, 592 and 604 mg/m3 for a single period of 20, 20 and 30 minutes, respectively (TNO, 1999).

A decrease in breathing rate or post-inspiratory apnoea were not seen in the breathing pattern. During exposure, no changes in behaviour were seen. No abnormalities or clinical signs were seen during

the 7-day observation period. None of the mice died. Dose (exposure*time) related weight decrease was not observed. Abnormalities at necropsy consisted primarily of discoloured areas on the lungs to a varying extent in the highest concentration group.

From the results of the present study in mice, it was concluded that a sensory irritation response of inhalable particles of multiconstituent aluminium potassium fluoride at the technically highest attainable concentration under the conditions of this study (604 mg/m3) was not found.