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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1994-01-10 to 1994-02-15
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Minor deviations from the OECD 403 guideline occurred, but they had no impact on the results of the study: - the humidity was <17 % for optimal dust distribution (recommended 30-70%) - the air change rate was slightly greater than 15/h. - no 95th percentile was calculated.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report date:
1994

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
1981-05-12
Deviations:
yes
Remarks:
see rational for reliability
GLP compliance:
yes (incl. QA statement)
Remarks:
signed 1991-07-25
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Sodium metavanadate
EC Number:
237-272-7
EC Name:
Sodium metavanadate
Cas Number:
13718-26-8
Molecular formula:
NaVO3
IUPAC Name:
sodium metavanadate
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): Sodium metavanadate
- Molecular formula: NaVO3
- Physical state: beige powder
- Storage condition of test material: at room temperature
- Particle size (geometric mean diameter): 9.08 µm (Malvern Mastersizer)

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS - Sprague-Dawley/Crl:CD R BR
- Source: Charles River Wiga GmbH, Niederlassung Sulzfeld, Sandhofer Weg 7, D-97633 Sulzfeld
- Age at start of adaptation: 35 - 50 days
- Weight at study initiation (immediately before exposure): males. 173 - 199 g; females: 173 - 192 g
- Fasting period before study: food was discontinued approximately 16 hours before exposition.
- Housing: granulated textured wood (type 2, supplied by: Johannes Brandenburg, D-49424 Goldenstedt-Arkeburg) was used as bedding material. During the 14- day observation period the animals were kept in group-caged by sex in groups of two or three in MAKROLON cages (type III).
- Diet (ad libitum): standardized diet for rats ALTROMIN 1324 (ALTROMIN GmbH, D-32791 Lage/Lippe)
- Water (ad libitum): tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22°C ± 3°C (maximum range)
- Relative humidity: 50% ± 20% (maximum range)
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
clean air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus/Exposure chamber volume/Method of holding animals in test chamber: the study was carried out using a dynamic inhalation apparatus (air changes/h. ≥ 12 x) with a nose only exposure of the animals according to KIMMERLE & TEPPER (RHEMA-LABORTECHNIK, D-65719 Hofheim/Taunus).
The apparatus consists of a cylindrical exposure chamber (volume 40 L) which holds a maximum of 20 animals in pyrex tubes at the edge of the chamber in a radial position.

- System of generating particulates/aerosols: the dust was generated with a rotating brush dust generator (RBG 1000, PALAS GmbH Partikel und Lasermesstechnik, D-76131 Karlsruhe. The generator was fed with compressed air from a compressor (air was taken from the surrounding atmosphere of the laboratory room and filtered using an in-line disposable gas-filter). At the bottom of the exposure chamber the air was sucked off at a lower rate than it was created by the dust generator in order to produce a homogenous distribution and a positive pressure in the exposure chamber.
Different concentrations were established by means of a combination of different settings of the dosing apparatus and different values of air flow.

- Method of particle size determination: an analysis of the particle size distribution was carried out during the first and during the second half of the exposure period using a cascade impactor according to MAY (MAY, K.R. 'Aerosol impaction jets', J. Aerosol Sci. 6, 403 (1975), RESEARCH ENGINEERS Ltd., London N1 5RD, UK).
The dust from the exposure chamber was sucked through the cascade impactor for 2 to 5 minutes at a constant flow rate of 5 L/min. The slides were removed from the impactor and were weighed on an analytical balance (SARTORIUS, type 1601 004, precision 10 µg).
The mass median aerodynamic diameter (MMAD) was estimated by means of nonlinear regression analysis (LITCHFIELD & WILCOXON). The 32 µm particle size range and the filter (particle size range < 0.5 µm) were not included in the determination of the MMAD in order not to give undue weight to these values.

- Treatment of exhaust air: the exhaust air was sucked through 3 gas wash-bottles filled with tap water. The outlet of the inhalation apparatus was in a DIN certified fume cupboard.

- Temperature, humidity, air flow and oxygen content: a manometer and an air-flow (Rotameter, ROTA Apparate- und Maschinenbau, D-79664 Wehr/Baden) were used to control the constant supply of compressed air and the exhaust, respectively. Flow rates were checked once per hour and corrected if necessary. Air changes per hour were 23 - 47.5.
The oxygen content in the inhalation chamber was 19%. The oxygen content was determined at the beginning and at the end of the exposure with a DRÄGER Oxygenanalysis test set (DRÄGER Tube Oxygen 67 28 081).
The exposure system was installed in a facility with a room temperature of 22°C ± 2°C and a relative humidity of 50% ± 20%.
Temperature (GTH 1200 Digital Thermometer, GREISINGER ELECTRONIC GmbH, D-93128 Regenstauf) and humidity (Sekunden-Hygrometer Typ 6100, TESTOTERM) within the inhalation chamber were measured and recorded once per hour (Temperature: 18.9°C - 21.9°C; humidity: 10.4% - 16.6%). Humidity within the inhalation chamber had to be kept at this low value in order to ensure an adequate particle size distribution.

Exposition started by locating the rats into the exposure chamber after equilibration of the chamber concentration for at least 15 minutes.

TEST ATMOSPHERE
- Brief description of analytical method used: the dust concentration in the inhalation chamber was measured with an air sample filter (SARTORIUS filter; Minisart SM 17598; 0.45 µm) and pump (Vacuubrand GmbH + Co., Otto-Schott-Straße 25, D-97877 Wertheim/Main). Dust samples were taken at least one every hour.
By means of a piece of silicon tubing, the filter was connected to an air flow meter (Rotameter, ROTA Apparate- und Maschinenbau, D-79664 Wehr/Baden) attached to the pump. The filters were weighed before and after sampling (accuracy: 10 µg)
- Samples taken from breathing zone: yes

TEST ATMOSPHERE
- MMAD (Mass median aerodynamic diameter):
0.48 mg/L air: 5.10 µm
2.58 mg/L air: 6.57 µm
4.13 mg/L air: 7.11 µm
- Respirable amount (particle size ≤4 µm):
0.48 mg/L air: 0.24 mg/L air
2.58 mg/L air: 0.62 mg/L air
4.13 mg/L air: 0.97 mg/L air
Analytical verification of test atmosphere concentrations:
yes
Remarks:
refer to "Details on inhalation exposure" above
Duration of exposure:
4 h
Concentrations:
Nominal concentrations:
2.11, 13.53 and 26.52 mg/L air
Actual concentrations:
0.48 ± 0.04, 2.58 ± 0.22 and 4.13 ±0.13 mg/L air
4.13 mg/L air was the highest amount of the test substance that could be generated in the inhalation chamber.
No. of animals per sex per dose:
5 males / 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: during and following exposure, observations were made and recorded systematically; individual records were maintained for each animal. A careful clinical examination was made at least once each day until all symptoms subsided, thereafter each working day.
Observations on mortality were made at least once daily with appropriate actions taken to minimize loss of animals to the study, e.g. necropsy or refrigeration of those animals found dead and isolation or sacrifice of weak or moribund animals.
Individual body weights of the animals were determined immediately before the exposure, after 1 week and at study termination.
- Necropsy of survivors performed: yes; necropsy of all animals was carried out and all gross pathological changes were recorded. Histopathology was not carried out as no relevant lesions were observed macroscopically.
Statistics:
The LC50 was calculated by means of regression analysis.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LC50
Effect level:
4.93 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: Slope: 11.0
Key result
Sex:
female
Dose descriptor:
LC50
Effect level:
3.73 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: Slope: 19.2
Sex:
male/female
Dose descriptor:
LC50
Effect level:
4.13 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: Slope: 15.1
Sex:
male
Dose descriptor:
LC0
Effect level:
4.13 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Sex:
female
Dose descriptor:
LC0
Effect level:
4.13 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
All deaths after end of exposure
0.48 and 2.58 mg/L air: no mortality
4.13 mg/Lair: 1 male (48 hours) and 4 females (0 - day 5)
Clinical signs:
other: All symptoms after end of exposure. 0.48 mg/L air: none 2.58 mg/L air: weak lacrimation (0 minutes; 1 male); weak salivation (0 minutes; 4 males and 4 females); nose and/or snout reddened (0 minutes; 4 males and 4 females); weak apathy (15 - 60 minutes;
Body weight:
No inhibition of body weight gain was observed.
Gross pathology:
0.48 and 2.58 mg/L air: no pathological findings
4.13 mg/L air: nose with haemorrhagic incrustation and small intestines distended were observed at 4.13 mg/L air in 1 deceased female, lungs with dark-red foci and a dark red liver were observed in another deceased female. These changes can be regarded as unspecific effects which usually occur after the inhalation exposure to a dust.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
LC50 (male rats): 4.93 mg/L air (analytical)
LC50 (female rats): 3.73 mg/L air (analytical)
LC50 (male and female rats): 4.13 mg/L air (analytical)
According to the EC-Regulation 1272/2008 and subsequent adaptations, the test item is classified acutely toxic via the inhalation route (Category 4).