Aluminum magnesium vanadium oxide

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

30 May - 14 Jun 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP - Guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

National Institute for Quality- and Organizational Development in Healthcare and Medicines, National Institute of Pharmacy, Budapest, Hungary

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

divanadium(5+) dialuminium(3+) magnesium(2+) nonaoxidandiide

EC Number:

692-448-4

Cas Number:

170621-28-0

Molecular formula:

Mg2xAl2xVyOz

IUPAC Name:

divanadium(5+) dialuminium(3+) magnesium(2+) nonaoxidandiide

Test material form:

solid: particulate/powder

Details on test material:

light yellow

Test animals

Species:

rat

Strain:

other: CRL (WI) BR of Wistar origin

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Toxi-Coop Zrt., Budapest, Hungary
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 229-239 g (males) and 184-188 g (females)
- Housing: animals were individually housed in Type II polycarbonate cages with certified laboratory wood bedding (Lignocel® Hygienic Animal Bedding, J. Rettenmaier & Söhne GmbH+Co. KG, Rosenberg, Germany).
- Diet: ssniff® SM R/M-Z+H complete diet (ssniff Spezialdiäten GmbH, Soest, Germany), ad libitum
- Water: drinking water, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70
- Air changes (per hr): 8-12
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 30 May 2012 To: 14 June 2012

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

>= 2.3 - <= 2.7 µm

Geometric standard deviation (GSD):

>= 3.05 - <= 3.29

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: anodised aluminium Flow Past Exposure Chamber (CR Equipment SA, Switzerland)
- Exposure chamber volume: 2.8 L
- Method of holding animals in test chamber: animals were held in polycarbonate restraining tubes
- Source and rate of air: filtered air at 15.9 L/min (0.99 L/min to each animal port)
- Method of conditioning air: the air was supplied by an oil-free air compressor and was filtered in a two-stage filter set. The temperature of the air was regulated by a heat exchanger.
- System of generating particulates/aerosols: dust aerosol generator type Wright (TSE Systems GmbH, Bad Homburg, Germany)
- Method of particle size determination: cascade impactor (IN-TOX Products, NM, USA)
- Temperature, humidity: 23.0-26.2 °C, 8.9-24.6%

TEST ATMOSPHERE
- Brief description of analytical method used: the atmosphere generated was measured gravimetrically at regular intervals (approx. 50 min) during exposure by pulling a volume of 5 L of test atmosphere from the exposure chamber through glass fibre filters (Fiberfilm T60A20, Pallflex Product Corp.). The duration of each sampling was 5 minutes. Sampling was performed 5 times: shortly after chamber equilibration and then at regular intervals during the exposure. Samples were collected from a vacant animal exposure port (animals' breathing zone). The actual sampling schedule employed was designed in order to obtain adequate quantities of test item. The achieved average concentration was calculated by combination of the gravimetric results and the recorded real-time data provided by the Aerosol Light Scattering Photometer integrated in the monitoring system of the exposure apparatus. The photometer was calibrated during the technical trials and the recorded data were corrected following the treatment according to the results of gravimetric concentration measurements. The test atmosphere concentration measurements were conducted also during sighting exposure.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: see Table 1 under “Any other information on materials and methods incl. tables")
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 2.5 µm/3.18 µm (main study); 3.4 μm/2.76 µm (sighting study)

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gravimetric and photometric (aerosol light scattering photometer)

Duration of exposure:

4 h

Concentrations:

SIGHTING STUDY:
- 5 mg/L (target concentration)
- 5.8 mg/L (analytical concentration)

MAIN STUDY:
- 5 mg/mL (target concentration)
- 4.852 mg/mL (analytical concentration)
- 16.3 mg/L (nominal concentration)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed for clinical signs at the first, second and third hour during exposure, as soon as practicable following removal from restraint, 1 hour after exposure and subsequently once daily during the 14-day observation period. Individual bodyweights were recorded prior to exposure (Day 0) and on Days 1, 3, 7 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Preliminary study:

A preliminary sighting exposure was performed at a target concentration of 5 mg/L (analytical concentration: 5.8 mg/L) in 1 male and 1 female rat for a period of 4 h. All animals survived the treatment and the following 96 h.

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 4.852 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No mortalities occurred during the whole study period.

Clinical signs:

other: No clinical signs of toxicity were noted up to the end of the 14-day observation period.

Body weight:

In both genders, body weight loss (-1.6% in males and -2.6% in females) was observed on the day of inhalation exposure. A compensation of body weight loss in males and females was found from Day 3 of the observation period.

Gross pathology:

No macroscopic findings were observed at necropsy.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

CLP: not classified