Ammonium trivanadium octaoxide

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

206-06-02 to 2006-08-23

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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 12 May 1981

Deviations:

no

GLP compliance:

yes

Remarks:

According to the study report, this study was performed in compliance with the GLP of OECD (OECD Environment Health and Saftey Publications, Series on Principles of GLP and Compliance Monitoring No. 1, Paris 1998.

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ammonium trivanadium octaoxide

EC Number:

235-384-0

EC Name:

Ammonium trivanadium octaoxide

Cas Number:

12207-63-5

Molecular formula:

NH4V3O8

IUPAC Name:

trivanadium(5+) ammonium octaoxidandiide

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): Ammoniumpolyvanadate ((NH4)2V6O16)
- Physical state: yellow powder
- Stability at conditions of storage: Stable
- Stability in aqueous solutions: Stable
- Storage condition of test material: Room temperature

Test animals

Species:

rat

Strain:

Crj: CD(SD)

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: approx. 9 weeks at time of administration
- Weight at study initiation: 214 g - 252 g
- Housing: Single caging in Makrolon cages type III (39 cm X 23 cm X 18 cm). Wire mesh lids. Bedding material: Aspen wood chips, Fa, ABEDD Dominik Mayr KEG, A-8580 Köflach, autoclaved.
- Diet (ad libitum): Altromin diet No. 1324 forte. No feed was offered during the exposure.
- Water (e.g. ad libitum): Acidified water to pH 3 with HCl, from watering system. No water was offered during the exposure.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: Group High concentration : mean of 24.1 °C; group Mid and low concentration: mean of 22.0 to 23.2 °C
- Relative humidity: Group High concentration: mean of 82 %; group Mid and low concentration: mean of 69 to 73 %
- Air exchange: 12 /h
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

other: air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- System of generating particulates/aerosols: The test substance was ground in a ball mill for 5 minutes. In the dust generator (Technical & Scientific Equipment GmbH, Kronberg, Germany, article number 594203) 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. 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.

- Exposure apparatus and exposure chamber volume: The test substance was administreed in a "nose-only" inhalation aparatus (TSE, Technical & Scientific Equipment GmbH, Kronberg, Germany; article no. 504101). It consisted of a two chamber system. The aparatus 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. The inhalation chamber was situated in a fume cupboard.

- Source and rate of air: The air was obtained from a central pressure pump. The air flow was 700 liter per hour.

- Treatment of exhaust air: The air escaped via the upper central opening and via the animal tubes. The air was filtered oil-free and distributed within the Research center

- Temperature, humidity, air flow: The relative humidity was reduced to about 10 %. 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 generator. During the exposure the air flow was checked by momentary interrupting the supply of the test substance and connecting the rotameter to the dust genereator. The air flow on the high pressure side (before the generator) was monitored by recording the pressure of the air.
The hygrometer was calibrated against the water vapour concentration of a saturated aqueous NaCl solution (76 % relative humidity) and a saturated LiCl solution (12 % relative humidity). The rotameter were calibrated against a gas meter (Experimentiergaszähler, Elster GesmbH, Vienna, Austria), which was calibrated by measuring the air displaced by a weighted volume water.
The temperature inside the chamber was 21.0 to 22.0 °C. The relative humidity ranged from 27 % to 35 %. The humidity was partly outside the recommeded range of 30 to 70 % but to prevent a possible agglomeration of the test substance, the air for the dust generation was not humidified.
- Other information: In the Toxicologiy Department the pressure was reduced to 1 bar.

TEST ATMOSPHERE (concentration of test substance)
- Brief description of analytical method used: The amount of test substance was measured by gravimetric analysis. The dust was collected 7 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 outer chamber. The inner diameter of the tips was 7 mm. Measured amounts of air with the dust were collected at a rate of 2.3 to 2.5 litres per minute which means a velocity of 1.0 to 1.1 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.
- Samples taken from breathing zone: no

- Method of particle size determination: The size if the dust particles was analysed with a cascade impactor (Berner-Impaktor Type LPI4/0,06/2 from Hauke KG, Gmunden, Austria). It contains nine steps with cut-off-diameters from 0.06 µm to 16 µm. The cut-off diameters were obtained from the manufacturer. The test substance - air mixture was passed through the impactor for 1 to 5 minutes at a rate of 5.7 L/min and the amount which sedimented in the individual steps was determined gravimetrically. The site of collection was the same as for the analysis

TEST ATMOSPHERE
- Particle size distribution for mid concentration group (1.23 mg/L) only : Fraction smaller that 5 µm: 86.5 %; fraction smaller than 4 µm: 77.2 %; fraction smaller than 2 µm: 35. 3%:
- MMAD (concentration of 0.47 mg/L): 2.5 (GSD: 1.8)
- MMAD (concentration of 1.23 mg/L): 2.5 µm (GSD: 1.9)
- MMAd (concentration of 2.67 mg/L): 2.6 µm (GSD: 1.8)
No further significant information on inhalation exposure was stated.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

see details on inhalation exposure

Duration of exposure:

4 h

Concentrations:

Mean Actual concentrations:
For the low concentration group: 0.47 mg/L
For the mid concentration group: 1.23 mg/L
For the high concentration group: 2.67 mg/L
Mean nominal concentration:
For the low concentration group: 3.6 mg/L
For the mid concentration group: 8.6 mg/L
For the high concentration group: 19.8 mg/L
The recovery of respirable dust was 13.1 to 14.3 %

No. of animals per sex per dose:

5 males / 5 females

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- 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 the expsoure and then at least once a day for a total of 2 weeks. Individual body weights were determined before administration, 7 days after administration, 14 days after administration and of dead animals, that deceased 1 day after administration or later.
- Necropsy of survivors performed: yes, deceased animals were dissected and examined macroscopically in an attempt to identify the target organs. 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.
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Body weight gain was calcualted for each week of the study i.e. between 0 and 7 days after administration and between 7 and 14 days after administration. Sex differences were evaluated.

Statistics:

For calculation of the mean particle size, the probit of the fraction of mass smaller than the cut-off diameters was plotted against the logarithm of the cut-off diameters and the linear regression of this graph was calculated, preferring the data points around 50 %. The diameter, where the regression gives a probit of 5 (corresponding to a fraction of 50 %) is the mass median aerodynamic diameter (MMAD). The proportion of the diameter at a probit of 6 (corresponding to a fraction of 84 %) to the mass median diameter is the geometric standard deviation (GSD).

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LC50

Effect level:

0.84 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Effect levels 2

Sex:

female

Dose descriptor:

LC50

Effect level:

1.08 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Effect levels 3

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

0.67 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

In the high (2.67mg/L) dose group, all animals died 2 hours to 1 days after the exposure.
In the mid (1.23 mg/L) dose group, all males and 3 of 5 females died 1 to 5 days after the exposure.
In the low (0.47 mg/L) dose group, one male but none of the females died 4 days after the exposure.

Clinical signs:

other: Dyspnoea and respiratory murmur were the most prominent findings in a dose-dependent severity. They indicate an adverse effect of the test substance to the lungs. Apathy and retention of faeces are interpreted as sequel of the bad condtions of the animals

Body weight:

The body weight loss in the first week after the exposure was test substance dependent. Males of the low-dose group lost 5.0 gram, in the mid- and high-dose groups, no male survived one week. Females of the low concentration group lost 9.2 gram, the two surviving females of the mid-dose group lost 5.5 gram. No female survived for one week in the high-dose group. In the second week, all survivng animals gained weight.

Gross pathology:

The most prominent findings were damages to the lungs (subpleural haemorrhages and oedema). Only decedents were affected.
Ulcer in the intestine and blood in the instestine 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 animasl died during the night.
In 5 animals of the mid- and high-dose groups, the anus of the animals was soiled with faeces.
The other findings, white foci in the liver, a small thymus, and thymus petechiae, were observed in one animal each and are maybe random events. Also, blood in the nose was observed in two males.

Other findings:

Males and females responded similary to the test substance.

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The inhalation exposure of rats to "ammonium trivanadium octaoxide" leads to adverse effects in the lungs at elevated concentrations. Subsequently, the oxygen exchange is decreased to an extent that becomes lethal in some cases. The LC50- via inhalation for four hours of "ammonium trivanadium octaoxide" for rats is:
LC50, inhalation, 4 h, male rats: 0.67 mg/L
LC50, inhalation, 4 h, female rats: 1.08 mg/L
LC50, inhalation, 4 h, male and female rats: 0.84 mg/L
For the classification of the test substance, the lower LC50 value is considered.
According to REGULATION (EC) No 1272/2008, "ammonium trivanadium octaoxide" should be labelled (Acute toxicity Category 3; H331: Toxic if inhaled).