Ammonium trioxovanadate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1992-01-13 to 1992-02-11

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

signed 1991-07-25

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ammonium trioxovanadate

EC Number:

232-261-3

EC Name:

Ammonium trioxovanadate

Cas Number:

7803-55-6

Molecular formula:

H4N.O3V

IUPAC Name:

ammonium trioxovanadate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): Ammonium metavanadate
- Physical state: light-beige, solid, amorphous powder
- Storage condition of test material: at room temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS - Sprague-Dawley/ Tif:RAI f (SPF)
- Source: Lippische Versuchstierzucht, HAGEMANN GmbH, D-4923 Extertal 1
- Age at study initiation: approximately. 40 - 60 days
- Weight at study initiation: males: 186 - 313 g; females: 175 - 215 g
- Fasting period before study: food was discontinued approximately 16 hours before exposition.
- Housing: granulated textured wood (type 2, supplied by: Johannes Brandenburg, D-2849 Goldenstedt) was used as bedding material. During the 14- day observation period, the animals were kept in groups of two or three in MAKROLON cages (type III).
- Diet (ad libitum): standardized diet for rats ALTROMIN 1324 (supplied by: ALTROMIN GmbH, D-4937 Lage/Lippe)
- Water (ad libitum): tap water
- Quarantine period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22°C ± 3°C (maximum range)
- Relative humidity: 60% ± 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 with a nose only exposure of the animals according to KIMMERLE & TEPPER (RHEMA-LABORTECHNIK, D-6238 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 dust generator and dosing apparatus (BURGHART, D-2000 Wedel/Holstein). The generator was fed with compressed air from a compressor. At the bottom of the exposure chamber the air was sucked off at a lower rate as created by the dust generator in order to produce a slight positive pressure in the exposure chamber.

- Method of particle size determination: an analysis of the particle size distribution was carried out twice during the exposure period using a cascade impactor according to MAY (1975) (MAY, K.R. 'Aerosol impaction jets', J. Aerosol Sci. 6, 403 (1975), RESEARCH ENGINEERS Ltd., (UK)-London N1 5RD).
The dust from the exposure chamber was sucked through the cascade impactor for 0.5 to 4 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 was not included in the determination of the MMAD in order not to give undue weight to this value.

- Temperature, humidity, air flow: air-flow meters (Rotameter, ROTA Apparate- und Maschinenbau, D-7867 Wehr 2/Baden) were used to control the constant supply of compressed air and vaccum. Flow rats were checked at least once/hour and corrected if necessary. Air changes per hour were 25.5.
The temperature (GTH 1200 Digital Thermometer, Fa. Greisinger Electronic GmbH, D-8413 Regenstauf) and humidity (Sekunden-Hygrometer Typ 6100, Testoterm) were continuously monitored close to the nose of the animals in the inhalation chamber. The temperature was 22°C ± 3°C and the relative humidity was 60% ± 20%.

Exposition started by locating the rats into the exposure chamber.

TEST ATMOSPHERE
- Brief description of analytical method used: the dust concentration in the inhalation chamber was measured with an air sample filter (Minisart N SM 17598; 0.45 µm) and pump (water jet air pump controlled by a rotameter). Dust samples were taken during the first half and during the second half of the exposure. Air was sucked through at the constant flow of air of 5 L/min for 1 to 4 minutes. The filters were weighed before and after sampling (accuracy 0.01 mg). Concentration of the test substance in the air was calculated as mg/L.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE
- MMAD (Mass median aerodynamic diameter):
0.72 mg/L air: 7.22 µm
1.21 mg/L air: 8.21 µm
1.54 mg/L air: 10.78 µm
2.20 mg/L air: 9.94 µm
3.49 mg/L air: 13.26 µm
- Respirable amount (particle size ≤4 µm):
0.72 mg/L air: 0.19 mg/L air
1.21 mg/L air: 0.26 mg/L air
1.54 mg/L air: 0.21 mg/L air
2.20 mg/L air: 0.35 mg/L air
3.49 mg/L air: 0.36 mg/L air

Analytical verification of test atmosphere concentrations:

yes

Remarks:

please refer to "Details on inhalation exposure" above

Duration of exposure:

4 h

Concentrations:

Nominal concentration:
males and females: 1.2, 1.5, 2.5 and 3.5 mg/L air
males only: 0.7 mg/L air
Actual concentrations:
male and female rats: 1.21 ± 0.09 , 1.54 ± 0.38, 2.20 ± 0.32 and 3.49 ± 0.91 mg/L air
male rats only: 0.72 ± 0.13 mg/L air
3.49 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 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. From animals which survived 24 hours or longer a microscopic examination of all organs which showed evident lesions was performed.

Statistics:

The LC50 (14 days) was calculated by regression analysis according to FINNEY.

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LC50

Effect level:

2.61 mg/L air (analytical)

Based on:

test mat.

95% CL:

1.69 - 4.03

Exp. duration:

4 h

Remarks on result:

other: Slope: 3.754

Effect levels 2

Sex:

female

Dose descriptor:

LC50

Effect level:

2.43 mg/L air (analytical)

Based on:

test mat.

95% CL:

1.82 - 3.24

Exp. duration:

4 h

Remarks on result:

other: Slope: 5.668

Effect levels 3

Sex:

male/female

Dose descriptor:

LC50

Effect level:

2.51 mg/L air (analytical)

Based on:

test mat.

95% CL:

1.95 - 3.23

Exp. duration:

4 h

Remarks on result:

other: Slope: 4.479

Effect levels 4

Sex:

male

Dose descriptor:

LC0

Effect level:

0.72 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Effect levels 5

Sex:

female

Dose descriptor:

LC0

Effect level:

1.21 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

0.72 mg/L air: no mortality
1.21 mg/L air: one male died 6 days after start of exposure
1.54 mg/L air: one female died 24 hours after start of exposure
2.20 mg/L air: three males and 2 females died between 2 and 3 days after start of exposure
3.49 mg/L air: three males and 4 females died between 24 hours and 7 days after start of exposure.

Clinical signs:

other: 0.72 mg/L air: no signs of systemic intolerance 1.21 mg/L air: piloerection (and lacrimation in 1 male) in 3 male animals on the first to third day of recovery 1.54 mg/L air: dyspnoea in 1 female animal on the first day of recovery 2.20 mg/L air: apathy,

Body weight:

No inhibition of body weight gain was observed.

Gross pathology:

0.72, 1.21 and 1.54 mg/L air: no pathological findings
Animals that died prematurely:
2.20 mg/L air: 2/2 females had noses with haemorrhagic incrustation
3.49 mg/L air: 1/3 male had a nose with haemorrhagic incrustation; 2/4 females had lungs with dark-red foci
These changes can be regarded as unspecific effects which usually occur after the inhalation exposure to a dust.
All further deceased animals showed no pathological findings.
Surviving animals (sacrificed (males and females):
no pathological findings

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

LC50 (male rats): 2.61 mg/L air (analytical)
LC50 (female rats): 2.43 mg/L air (analytical)
LC50 (male and female rats): 2.51 mg/L air (analytical)
The no-effect-level was 0.72 mg/L air for 4 hours for males and 1.21 mg/L air for females.
According to the EC-Commission directive 67/548/EEC and its subsequent amendments, the test substance is classified as harmful by inhalation.
According to the EC-Regulation 1272/2008 and subsequent regulations, the test item is classified as Category 4.