Magnesium diniobate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2000-10-11 to 2000-11-03

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

1981-05-12

Deviations:

no

GLP compliance:

yes

Test type:

traditional method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Diniobium pentaoxide

EC Number:

215-213-6

EC Name:

Diniobium pentaoxide

Cas Number:

1313-96-8

Molecular formula:

Nb2O5

IUPAC Name:

Diniobium pentaoxide

Test material form:

solid: particulate/powder

Details on test material:

- State of aggregation: white powder

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: in the dark at ambient room temperature (approx. 20 °C( and in the original container

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: test substance was hand ground with a pestle and mortar prior to use.

Test animals

Species:

rat

Strain:

other: Crl: CD® (SD) IGS BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK Limited, Manston Road, Margate, Kent, England
- Age on day of arrival: males: approx. 7 weeks old; females : approx. 8 weeks old
- Housing: housed by sex, in groups of 5; holding cages were made of stainless steel sheet and wire mesh and were suspended on a movable rack
- Diet (ad libitum): SDS rat and mouse diet (RM1 (E) SQC expanded pellet)
- Water (ad libitum): tap water
- Acclimation period: 9 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19.5 °C to 20.5 °C
- Relative humidity: 39 % to 68 %
- Air changes: at least 15 changes/hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

clean air

Mass median aerodynamic diameter (MMAD):

3.3 µm

Geometric standard deviation (GSD):

1.88

Remark on MMAD/GSD:

Approx. 88 % of the particulate were considered of a respirable size (< 7 µm in aerodynamic diameter)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: snout-only exposure chambers (ADG Developments Ltd., Hitchin, Hertfordshire, England) used for the exposures were of cylindrical form (30 cm diameter, 45 cm height) and made of aluminium alloy. The internal surfaces of the chamber have a conformal chemically resistant coating.
The conditioned test atmosphere entered through a port at the top centre of the chamber and passed out through a port at the base section below the level of the animals.
The exposure system was positioned inside a large cabinet equipped with an extract fan exhausting to atmosphere through an absolute filter.

- Exposure chamber volume: approx. 30 litres

- Method of holding animals in test chamber: animals were held for exposure in moulded polycarbonate restraining tubes, which were attached at evenly spaced ports in the cylindrical section of the chamber, and were designed to allow only the snout to project into the chamber. Each animal was restrained in a forward position by an adjustable foamed plastic stopper, which also provided a seal for the tube.

- System of generating particulates/aerosols: a 'Fast' Wright Dust Feed mechanism (WDF; speed controller setting: 70 % of max. speed (based on preliminary generation)) was used to produce the test atmosphere containing a particulate aerosol generated from the hand ground test item. Test item was packed into the container of the WDF using a hydraulic bench press to assist packing. An even density of the test substance was achieved by packing the container in stages and applying a force of 2.5 ton to compress the powder. The packed container was weighed.
The WDF was designed to produce and maintain atmospheres containing a particulate aerosol by suspending material scraped from the surface of a compressed powder in a stream of dry air. The concentration of particulate aerosol in the air is determined by the rate at which the scraper blade is advanced into the compressed powder.
A jet was fitted to the WDF to break-up aggregates emitted from the aerosol generator.
In order to prevent a build-up of electrostatic charge from the aerosol, earth leads were added to both the WDF and the chamber.
A supply of clean, dry air was connected to the generator and the supply pressure was adjusted to give a flow rate of 15 L/minute. A neutralised diluent air supply, adjusted to give 10 L/minute, was connected to the elutriator to provide a total air supply of 25 L/minute.
In-line flow meters were used to monitor the generator and diluent air supplies and exhaust airflow throughout the exposure. The exhaust airflow was calibrated and adjusted to produce a slightly negative pressure.
The output of the WDF was connected to the top inlet port of the chamber via a horizontal glass elutriator to reduce, by sedimentation, the amount of non-respirable particulate in the test atmosphere. A neutralised air flow was passed externally over the elutriator to remove any electrostatic charge.

After the exposure system was allowed to equilibrate for 3 minutes (t90%), the exposure period of 4 hours was started.

- Method of particle size determination: two air samples were taken during the exposure at a sampling rate of 2 L/minute using a Marple cascade impactor (Model 298; Graseby Andersen Inc.) to determine particle size distribution. The samples were taken at 102 and 212 minutes into exposure. The volume of air sampled was measured using a wet-type gas meter.
The amount of material collected on the stages of the sampler was determined gravimetrically. The particle size distribution of the test atmosphere was assessed using linear regression analysis. The probit of the cumulative percentage of the total particles collected, smaller than the cut-point of each stage, was plotted against the logarithm of the cut-point of each stage.

- Temperature and humidity: air temperature in the exposure chamber was measured using an alcohol-in-glass thermometer and the relative humidity was measured using a Casella type T6900 relative humidity meter. The temperature and relative humidity were recorded at the start of exposure and then at 30-minute intervals during the 4-hour exposure.
Temperature (mean): 20.0 ± 0 °C (control group) and 19.9 ± 0.17 °C (test group)
Relative humidity (mean): 42 % ± 1.7 (control group) and 59 % ± 1.3 (test group)

TEST ATMOSPHERE
- Brief description of analytical method used: seven samples of air were removed from the test chamber during exposure in order to determine the concentration of the test aerosol. Samples were obtained following equilibration and generally at approx. hourly intervals thereafter. Additional samples were obtained as necessary to monitor the chamber concentration.
Each air sample was withdrawn, at a rate of 2 L/minute, through a pre-weighed glass fibre filter (Schleicher & Schuell GF/50 filters). The volume of air sampled was measured using a wet-type gas meter (Model DM3B; G.H. Zeal Ltd.). The filters were re-weighed following sampling for gravimetric analysis of the test aerosol.
- Samples taken from breathing zone: yes

Analytical verification of test atmosphere concentrations:

yes

Remarks:

see above "Details on inhalation exposure"

Duration of exposure:

4 h

Concentrations:

actual concentration: 5.45 ± 0.596mg/L
nominal concentration: 26.1 mg/L
target concentration: 5 mg/L

No. of animals per sex per dose:

5 males / 5 females

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing:
mortality/moribund: at least twice daily (once in the morning and again towards the end of the normal working day)
clinical signs: at the end of the chamber equilibration period, at 0.25, 0.5 and 1.0 hours then at hourly intervals during the exposure as well as immediately following exposure and then at 1.0 and 2.0 hours post-exposure. During the remaining observation period, once in the morning and then as necessary following a later check for survival.
body weight: at least twice during the week prior to exposure, prior to exposure (Day 0), weekly during the observation period and on the day of death.
water consumption: daily (visual inspection)

- Necropsy of survivors performed: yes, all animals were subjected to a detailed macroscopic examination. The lungs (including the larynx and trachea) were removed and weighed.

Statistics:

not applicable

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.45 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

There were no unscheduled deaths.

Clinical signs:

other: - during exposure: exaggerated breathing was observed in most test rats from 1 hour, and all test rats from 2 hours into exposure. - observation period: exaggerated breathing was evident in all test rats immediately post exposure, persisting to Day 4 of t

Body weight:

A slightly reduced mean body weight gain was evident for male test rats during the first week following exposure. Thereafter, the mean bodyweight gain was similar to that of the control values.
Body weight gain values of the female test rats was similar to that of the control values.

Gross pathology:

No treatment-related findings were noted at necropsy.

Other findings:

- organ weights: no treatment-related effects were noted for lung weights.
- water consumption: no treatment-related effects were observed.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

LC50 (male and female rats) > 5.45 mg/L (analytical concentration)
According to the Regulation (EC) No 1272/2008 and subsequent adaptations, the substance is not acutely toxic via the inhalative route.