Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
14th March 2006 to 1st August 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report date:
2006

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Version / remarks:
92/69/EEC and 93/21/EEC
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Dipotassium heptafluorotantalate
EC Number:
240-986-1
EC Name:
Dipotassium heptafluorotantalate
Cas Number:
16924-00-8
Molecular formula:
F7Ta.2K
IUPAC Name:
Tantalate(2-), heptafluoro-, potassium (1:2)
Test material form:
solid: crystalline
Details on test material:
- Name of test material (as cited in study report): Dikaliumheptafluorotantalat (Kaliumtantalfluorid)
- Substance type: White crystals
- Storage condition of test material: Room temperature, tightly closed, dry.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland GmbH, D-97633
- Age at study initiation: Approximately 9 weeks at time of administration.
- Weight at study initiation: 288g - 321g males, 214 - 235g females.
- Housing: Individually caged in Makrolon cages type lll (39 cm x 23 cm x 18 cm). Wire mesh lids. Cages sanitised weekly.
- Diet: Altromin diet No. 1324forte ad libitum. None during exposure.
- Water: Acidified water to pH 3 with HCl, taken from a watering system. Ad libitum excluding exposure period.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 21.1 to 23.5 ºC
- Humidity: range 39.8 to 79.4%
- Air changes: 12 per hour
- Photoperiod: 12 hours of artificial light/12 hours darkness

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Nose only apparatus
- Exposure chamber volume: 19 litres
- Source and rate of air: Air obtained from a central pressure pump at 700 L/h
- System of generating particulates/aerosols: The test material was stirred in the dust generator and trickled onto an adjustable metering system. It then fell into the aerosol flask, where it was picked up by an air flow and transported to the lower centre of the inhalation chamber. The metering system was adjusted to get the desired dust concentration.
- Method of particle size determination: anaylsed by cascade impactor (Berner-Impaktor Type LP14/0,06/2 from Hauke KG, Gumunden, Austria). Approximately 8 to 14 litres of the test material-air mixture was passed through the impactor within 1.5 to 2.5 minutes and the amount which sedimented was determined gravimetrically. The mean particle size was calculated.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: Preliminary experiments provided information for the starting concentration. As less than half of the animals of groups 1 and 2 died, the concentration of the dust was increased for the following group.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
Analysed: Low dose 0.77 mg/L, mid dose 1.84mg/L and high 4.38mg/L
No. of animals per sex per dose:
5 males and 5 females per dose
Control animals:
yes
Details on study design:
- Duration of observation period following administration: Test animals were observed 1, 2, 3, 4, 5, and 6 hours after the start of exposure then at least once a day for a total of 14 days.
- Frequency of observations and weighing: body weights were observed before administration then at 7 and 14 days post exposure.
- Necropsy of survivors performed: yes, 14 days post exposure.
- Other examinations performed: Deceased animals were examined macroscopically, to identify target organs. Surviving animals were sacrificed and subject to a necropsy and pathological examination. The microscopic anatomy of two test animals' lungs were examined under a light microscope, after fixing in Bouin's solution.
Statistics:
None reported

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LC50
Effect level:
6.8 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: confidence limits not reported
Sex:
female
Dose descriptor:
LC50
Effect level:
2.1 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: confidence limits not reported
Sex:
male/female
Dose descriptor:
LC50
Effect level:
3.3 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: confidemce limits not reported
Mortality:
Within the high dose group 2 males and 4 females died 1 to 7 days post exposure.

In the mid dose group 1 male died 3 days post exposure. One female died 2 days post exposure with another female being sacrificed moribund 3 days post exposure.

In the low dose group 1 female was sacrificed moribund 3 days after exposure.

A synopsis of these results can be seen in the field " Any other information on results incl. tables".
Clinical signs:
other: Dyspoea and respiratory murmur were the most prominent findings in a dose dependent severity. They indicate an adverse action of the test material to the lungs. Piloerection, sedation or apathy, chromodacryorrhoea, hunched posture and closed eyes are sig
Body weight:
All surviving rats in the low and mid dose groups continued to gain weight after exposure. High dose males and females lost weight in the first week, then gained weight in the second week.

Week 1 values:
Low dose males gained 18 g
Mid dose males gained 8g
High dose males lost 37g

Low dose females gained 3g
Mid dose females gained 10 g
The sole remaining high dose female lost 71 g.

Figures are based on mean averages.
Gross pathology:
Prominent findings were damage to the lungs, only those which died were affected.

All other findings were attributed to the poor condition of the test animals:
- Emaciation, exsiccosis due to weight loss.
- Meteorism and empty intestine consequential of the animals’ refusal to feed.

The following were seen in high dose animals:
- Sanguineous secretion at the nose was observed in 6 animals.
- A fibrin plug was found in the larynx of 2 males.

Histopathology observations:
-Local destruction of lung tissue in the lower airways and the alveoli with some reactive inflammation.
-Bacteria were seen to have started to grow within the necrotic material.

Any other information on results incl. tables

Table 1. Synopsis of Mortality Results

Sex Concentration mg/L Number of Animals
    dead (time of death) affected exposed
male 4.38 2 (1d - 3d) 5 5
female 4.38 4 (3d - 7d) 5 5
male 1.84 1 (3d) 3 5
female 1.84 2 (2d - 3d)* 3 5
male 0.77 0 0 5
female 0.77 1 (3d)* 1 5

*indicates one animal of this group was moribund and therefore killed

Applicant's summary and conclusion

Interpretation of results:
other: Category 4 (Harmful)
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the test, the test material caused local tissue destruction in the lungs when administered by inhalation to rats. This was followed by a decrease in oxygen exchange to an extent that became lethal in some cases. The LC50 values were determined to be 6.8 mg/l (males), 2.1 mg/l (females) and 3.3 mg/l (males and females). Therefore the test material is classified as harmful by inhalation.
Executive summary:

In a GLP compliant acute inhalation study conducted in accordance with OCED Guideline 403 and EU method B.2, the acute inhalation toxicity of the substance was determined. Rats were exposed to three concentrations of the test material for a period of four hours. Under the conditions of the test, the test material caused local tissue destruction in the lungs when administered by inhalation to rats. This was followed by a decrease in oxygen exchange to an extent that became lethal in some cases. The LC50 values were determined to be 6.8 mg/l (males), 2.1 mg/l (females) and 3.3 mg/l (males and females).

Under the conditions of the study, the test material was considered to be harmful by inhalation. The test material requires classification as Harmful (Xn) with the associated risk phrase R20 “Harmful by inhalation" under Directive 67/548/EC. Under Regulation 1272/2008 the test material requires classification as "Acute Tox. 4" with the associated hazard statement "H332: Harmful if inhaled".