Ammonium sodium vanadium oxide

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Study period:

2006-08-03 to 2006-09-06

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

GLP guideline study reliable without restrictions Deviations from the OECD 403 guideline occurred, but they had no impact on the results of the study: - the humidity in the animal room was temporarily higher than 70 % (maximum of 79%). - no information about O2-content was given.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

adopted 1981-05-12

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

sodium trivanadium octaoxide

IUPAC Name:

sodium trivanadium octaoxide

Constituent 2

Reference substance name:

Sodium trivanadium octaoxide

EC Number:

234-709-3

EC Name:

Sodium trivanadium octaoxide

IUPAC Name:

234-709-3

Constituent 3

Reference substance name:

12026-08-3

Cas Number:

12026-08-3

IUPAC Name:

12026-08-3

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): "Sodiumpolyvanadate (SPV)"
- Chemical name: Sodiumpolyvanadate
- Molecular formula: Na2V6O16
- Physical state: auburn powder
- Stability at conditions of storage: stable
- Storage condition of test material: room temperature
- Water solubility: hardly soluble
- Stability in aqueous solutions: stable

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS - Crl: CD(SD)IGS BR, Sprague-Dawley, SPF
- Source: Charles River Deutschland GmbH, D-97633
- Age at study initiation: approx. 9 weeks at time of administration
- Weight at study initiation: males: 314 - 348 g; females: 218 - 249 g
- Housing: single caging in Makrolon cages type III (39 cm x 23 cm x 18 cm). Wire mesh lids. Aspen wood chips, Fa. ABEDD Dominik Mayr KEG, A-8580 Köflach, autoclaved.
- Diet (ad libitum, except during exposure): Altromin diet No. 1324 forte
- Water (ad libitum, except during exposure): acidified water to pH 3 with HCl
- Acclimation period: 5 days

Nibbling wood bricks (10 cm x 2 cm x 2 cm) and nesting material, both from the same material and source as the bedding material, were offered to the animals once a week

ENVIRONMENTAL CONDITIONS
- Temperature: mean of 22°C
- Relative humidity: mean of 66%
- Air exchanges: 12/hour
- 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 test substance was administered in a 'nose-only' inhalation apparatus (TSE, Technical & Scientific Equipment GmbH, Kronberg, Germany; article no. 504101). It consisted of a two chamber system. The apparatus was 30 cm in diameter and 27 cm in height, resulting in a total volume of 19 litres. In the twenty openings of the outer chamber, the inhalation tubes with the animals were situated. As only ten animals were administered, only the openings in the upper row were used. Neither feed nor water was offered to the animals during the exposure.
The inhalation chamber was situated in a fume cupboard.

- Source and rate of air: the air was obtained from a central pressure pump. The relative humidity was reduced to about 10%. The air was filtered oil-free and distributed within the laboratory. The pressure ws reduced to 1 bar.

- System of generating particulates/aerosols: a dust generator from Technical & Scientific Equipment GmbH, Kronberg, Germany, article number 594203 was used.
The test substance was ground in a ball mill for 5 minutes to improve the output of respirable dust. In the dust generator it was trickled on to an adjustable metering system. From there it fell into the aerosol flask, 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. The air flow was 700 L per hour. Larger particles, the main part of the test substance, were caught in the inner chamber by sedimentation. Smaller particles reached the outer chamber and the inhalation tubes with the animals.

- Method of particle size determination: The size of the dust particles was analysed with a cascade impactor (Berner-Impaktor Type LPI4/0, 06/2 from Hauke KG, Gmunden, Austria).
The test substance - air mixture was passed through the impactor for 1 to 2.5 minutes at a rate of 5.7 L/min.
The mass median aerodynamic diameter (MMAD) was calculated by linear regression.

- Treatment of exhaust air: the air escaped via the upper central opening and via the animal tubes.

- Temperature, humidity, air flow: the humidity of the air inside the chamber was measured with a hygrometer (Hygrotest serie 55, type 0555 6020, Testoterm Ges.m.b.H., Vienna, Austria), the temperature with a glass-mercury thermometer. The air flow on the low pressure side (after the generator) was measured with a rotameter (Rota Apparatebau GmbH&Co KG, Wehr, Germany, type L 63/2400-9048, ranging till 2000 L/h) before starting the dust generation. During the exposure the air flow was checked by momentary interrupting the supply of the test substance and connecting the rotameter to the dust generator. The air flow on the high pressure side (before the generator) was monitored by recording the pressure of the air.
The temperature inside the chamber was 20.8 to 22.4°C. The relative humidity ranged from 28% to 34%. The humidity was partly outside the recommended range of 30 to 70% but to prevent a possible agglomeration of the test substance, the air for the dust generation was not humidified.

TEST ATMOSPHERE
- Brief description of analytical method used: the amount of test substance was measured by gravimetric analysis.
The dust was collected 11 to 12 times during each exposure in plastic pipette-tips filled with cotton-wool which were inserted into the inhalation facility through a separate hole between two inhalation tubes. The site of collection was within the other chamber. The inner diameter of the tips was 7 mm. Measured amounts of air with the dust were collected at a rate of 2.6 to 2.7 litres per minute which means a velocity of 1.1 to 1.2 m/sec in the tips. The exact amount of collected air was measured by a gas meter (Experimentiergaszähler, Elster GesmbH, Vienna, Austria).
Each filter-tip was dried and weighed before sampling. After sampling dry air (<10% humidity) was passed through them until the weight was constant. The difference in the weights before and after sampling divided by the volume of air sampled is the concentration of the dust.

The nominal chamber concentration was calculated as the weight of test substance used divided by the air flow through the chamber.

TEST ATMOSPHERE
MMAD (Mass median aerodynamic diameter)
- 0.62 mg/L: 2.9 µm (GSD: 2.1)
- 1.06 mg/L: 3.1 µm (GSD: 2.1)
- 1.91 mg/L: 2.6 µm (GSD: 2.3)

- Rationale for the selection of the concentration: according to the results with a similar substance, the target concentration of the first group was set. The concentrations of the succeeding groups were set according to the results of the previous groups.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

please refer to "Details on inhalation exposure" above

Duration of exposure:

4 h

Concentrations:

Nominal concentrations:
8.57, 14.3 and 24.3 mg/L
Actual concentrations:
0.62 ± 0.05, 1.06 ± 0.07and 1.91 ± 0.15 mg/L

The recovery of respirable dust therefore was 7.2 to 7.9%.

No. of animals per sex per dose:

5 males / 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 2 weeks
- Frequency of observations and weighing: behaviour, reactions and physical signs of each of the animals were observed 1, 2, 3, 4, 5 and 6 hours after the start of exposure and then at least once a day for a total of 2 weeks.
Individual body weights were determined before administration as well as 7 and 14 days after administration. The body weight of dead animals, that deceased 1 day after administration or later was also recorded. Body weight gain was calculated for each week of the study, i.e. between 0 and 7 days as well as 7 and 14 days after administration.
- Necropsy of survivors performed: yes, surviving animals were killed by CO2-asphyxia (80% CO2 and 20% air) 14 days after administration and subjected to a necropsy including a gross pathological examination.
Deceased animals were dissected and examined macroscopically in an attempt to identify the target organs.

Statistics:

no data

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LC50

Effect level:

1.18 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Effect levels 2

Sex:

female

Dose descriptor:

LC50

Effect level:

1.73 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Effect levels 3

Sex:

male/female

Dose descriptor:

LC50

Effect level:

1.57 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

0.62 mg/L: all animals survived until the end of the observation period
1.06 mg/L: 3 males died 3 to 8 days after the exposure.
1.91 mg/L: 3 males and 3 females died 3 hours to 6 days after the start of the exposure.

Clinical signs:

other: The heads of the animals were stained brown from the test substance after the exposure. Animals without severe effects cleaned themselves within one day, animals of the 1.06 and 1.91 mg/L dosed groups needed up to 5 days or did not clean themselves until

Body weight:

0.62 mg/L: all but one animals gained weight in the first week after exposure.
1.06 mg/L: all males lost weight in the first week. Within the females some lost and some gained weight. This is a sequel of the reduced well-being due to the test substance exposure. All deceased animals lost weight.
1.91 mg/L: all males lost weight in the first week. Within the females some lost and some gained weight. This is a sequel of the reduced well-being due to the test substance exposure. All deceased animals lost weight.

In the second week all but one suriving animals gained weight.

Gross pathology:

Only decendents were affected.
The most prominent findings were adverse effects to the lungs (subpleural haemorrhages, oedema, irritation).
Erosion in the stomach and blood in the intestinal lumen indicated that probably some of the test substance was also ingested orally. The intestine of some animals was autolytic at the time of necropsy as the animals died during the night.
In 1 animal of the 1.06 mg/L dosed group the anus was soiled with faeces.
The other findings, a small thymus, and a small spleen, were observed in one animal and are probably sequels of the general bad condition of the animal.

Other findings:

- Other observations: males and females responded similarly to the test substance. Males were the more sensitive gender according to the mortalities and the body weight development.

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; 4 hours): 1.18 mg/L
LC50 (female rats; 4 hours): 1.73 mg/L
LC50 (male and female rats; 4 hours): 1.57 mg/L
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.