Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
- Name of test material (as cited in study report): Potassium tetrafluoroborate
- Physical state: White powder
- Analytical purity: 99.1%
- Storage condition of test material: At room temperature in the dark
- Lot/batch No.: BWF10626
- Expiration date of the lot/batch: 31 July 2013

Test animals

Species:
rat
Strain:
other: Wistar outbred (Crl: WI[Han])
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories
- Age at study initiation: 9 weeks
- Weight at study initiation: 263 and 186 g for males and females, respectively
- Fasting period before study: no (only during exposure)
- Housing: macrolon cages with a bedding of wood shavings (Lignocel, Type ¾) and a wooden block and strips of paper (Enviro-dri) as environmental enrichment (3 male or 3 female animals per cage).
- Diet: cereal-based (closed formula) rodent diet (Rat & Mouse No. 3 Breeding Diet, RM3) from a commercial supplier (SDS Special Diet Services, Whitham, England), ad libitum
- Water: domestic mains tap-water, ad libitum
- Acclimation period: 11 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 45-65
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: a cylindrical stainless steel column, surrounded by a transparent cylinder. The column had a volume of ca. 50 litres and consisted of a top assembly with two mixing chambers, a rodent tube section and at the bottom the base assembly with the exhaust port. The rodent tube section had 20 ports for animal exposure.
- Method of holding animals in test chamber: the animals were secured in plastic animal holders (Battelle), positioned radially through the outer
cylinder around the central column. The remaining ports were closed. Only the nose of the rats protruded into the interior of the column.
- Source of air: fresh test atmosphere.
- System of generating particulates/aerosols: Since the aerodynamic particle size of the original test material was above the range of 1-4 μm recommended by OECD guideline 436, the test material was milled using a ball mill fitted with a zirconium beaker and 99 zirconium balls with a diameter of 10
mm. Among a few alternative milling scenarios, a five-fold repetition of milling during 5 minutes at a speed of 500 rotations per minute followed by a 1-minute pause with reversal of the direction of rotation after each pause resulted in a powder that could be aerosolized with a MMAD (mass median aerodynamic particle size) below 4 μm. The test material was aerosolized using a turntable dust feeder, a venturi and a jetmill. The venturi was supplied with humidified compressed air and operated at a pressure of 1.0 bar; the jetmill was supplied with dry compressed air and operated at 5.0 bar. The test atmosphere, exhausted from the jetmill at the top inlet of the exposure unit, was directed downward and led to the noses of the animals. At the bottom of the unit the test atmosphere was exhausted. The animals were placed in the exposure unit after stabilization of the test atmosphere. The period between the start of the generation of the test atmosphere and the start of exposure of the animals was 32 minutes.
- Method of particle size determination: carried out using a 10-stage cascade impactor (2110k, Sierra instruments, Carmel Valley, California, USA). The Mass Median Aerodynamic Diameter (MMAD) and the geometric standard deviation (gsd) were calculated.
- Air flow rate: ≥1 litre/min for each rat.
- Temperature, humidity, pressure in air chamber: controlled at a temperature of 22 ± 2°C and 30-70% relative humidity.

TEST ATMOSPHERE
- Brief description of analytical method used: by means of gravimetric analysis.
- Samples taken from breathing zone: yes
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
- Target limit concentration: 5 g/m3
- actual concentration during exposure: 5.3 ± 0.7 g/m3
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed for clinical abnormalities during exposure, shortly after exposure and daily thereafter, body weight was measured before exposure (day 0) and 1, 3, 7 and 14 days after exposure
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5 300 mg/m³ air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
Mortality did not occur.
Clinical signs:
- During exposure: a slightly decreased breathing rate was observed in all animals at the last two hourly observation time points.
- 1 hour after exposure: no exposure-related clinical abnormalities noted.
- 2 hours after exposure: soiled fur was noticed in two females, one of which also showed lethargic behaviour.
- During 14 day observation period: no clinical abnormalities noted.
Body weight:
One day after exposure, all animals showed a slight loss of body weight. Recovery of body weight was observed in most animals by day 3. A slightly delayed recovery was observed in one female, which reached its pre-exposure body weight by day 7. Body weight development in the second week of the 14-day observation period was considered within the normal range for this strain and age of rats.
Gross pathology:
Macroscopic abnormalities at necropsy were limited to a few findings in the lungs. Petechiae were found in single lung lobes of 2 males and 1 female, two other animals (1 male, 1 female) had pale lungs. No further macroscopic abnormalities were observed.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the observations the LC50 of the test substance is greater than 5300 mg/m³
Executive summary:

In a GLP-compliant acute inhalation study performed according to OECD Guideline 436, 3 male and 3 female rats were exposed to potassium tetrafluoroborate. The animals were exposed, nose only, for a 4 -hour period to a target concentration of 5 g/m3 (the analytical concentration was 5.3 ± 0.7 g/m3) potassium tetrafluoroborate. Animals were observed for 14 days before sacrifice. During the second half of the exposure, all animals showed a slightly decreased breathing rate. No clinical abnormalities were observed approximately one hour after exposure; two hours after exposure soiled fur was seen in two females, one of which also demonstrated lethargic behaviour. One day after exposure, all treatment-related abnormalities had disappeared. After an initial loss of body weight upon exposure normal body weight development was observed 3 days (five animals) and 7 days (one animal) after exposure. No deaths occurred. Macroscopic abnormalities at necropsy were limited to petechiae in single lung lobes of three animals and pale lungs in two other animals. Although it cannot be excluded that these findings were related to the exposure, the minor macroscopic abnormalities in the lungs may well have been part of common background pathology. Based on these findings, the 4-hour LC50 in rats was determined at >5.3 g/m3.