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Acute Toxicity: inhalation

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acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
11 October 2000 - 03 November 2000
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study

Data source

Reference Type:
study report
Report date:

Materials and methods

Test guideline
according to guideline
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method

Test material


Test animals

Details on test animals or test system and environmental conditions:
Tem male and 10 female albino rats were selected from a consifnment of animals obtained from Charles River UK Limited, Manston Road, Margate, Kent, England on October 2000. The animals were ordered so that males and females would be approximately 7 and 8 weeks old respectively on the day of arrival.
On arrival the animals were allocated to 1 of 2 groups, each of 5 males and 5 females and were identified individually by a number tattooed on the ear pinnae and on the right hind foot to indicate 100’s. The animals were housed by sex, in groups of 5 and acclimatized to laboratory conditions for 9 days before the day of exposure. Data from Group 1 (control) animals were also reported as concurrent controls in study numbers SKC/015 and SKC/024.
The holding cages were made of stainless steel sheet and wire mesh and were suspended on a movable rack. While in their cages all animals had free access to an excess amount of food, DSD rat and mouse diet (RM1 (E) SQC expanded pellet), and tap water supplied by Anglian Water. Tap water was available from individual polypropylene water bottles that were emptied and re-filled daily. There was no information available to indicate to the Study Director the presence, in the food or water, of any non-nutrient substance likely to influence the outcome of this study. The results of chemical analyses on batches of diet and water supplied to the animals during this study are lodged in the Huntingdon Life Sciences Archives.
The animals remained in a holding room except for the 4-hour exposure and an overnight post exposure period when the animals in the test group were kept in a ventilated cabinet to allow dispersal of any residual test substance.
The temperature and relative humidity of the animal room were recorded continuously using a Kent Clearspan recorder. The room conditions were maintained within the environmental control settings of 22°C +/- 3 for temperature and 50% +/- 20% for relative humidity.
Temperature maximum: 20.5°C
minimum: 19.5°C
Relative humidity maximum 68%
minimum 39%
Air extraction was via a balanced system providing at least 15 air changes per hour. Room lighting was controlled to give 12 hours light (06:00 – 18:00 GMT) and 12 hours dark per 24 hours.

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
clean air
Details on inhalation exposure:
A single group of animals was exposed continuously for 4 hours to a test atmosphere containing a particulate aerosol generates from hand ground Nb2O5 NIOBIUM PENTOXIDE GRADE LN.
A further group acting as a control received clean air only for 4 hours.
The group identification and date of exposure for the groups were:
Group 1 (control): 20 october 2000
Group 2 (Test): 20 october 2000
Analytical verification of test atmosphere concentrations:
Duration of exposure:
4 h
Chamber concentration of Nb2O5 NIOBIUM PENTOXIDE GRADE LN
The mean chamber concentration was 5.45 mg/l and was in good agreement with target (5 mg/l).

Nominal concentration
The nominal concentration was 26.1 mg/l. The mean chamber concentration was 20.9% of the nominal concentration and reflects losses of the test material due to impaction and deposition with the exposure system. When generating Niobium pentoxide static agglomeration was considered to be a significant factor in the particulate losses within the aerosol generation system. The use of a neutralized air supply, both to the WDF and diluents supply, was necessary to achieve the concentration attained. In addition, neutralized air was passed over the external surface of the elutriator to reduce electrostatic losses. The relatively low efficiency observed in this study is not unusual for the exposure system and test compound employed.

Particle size distribution
The mass median aerodynamic diameter (MMAD) of the test aerosol was 3.3m and was within the acceptable range (1m to 4 m) for an acute inhalation study. Approximately 88% of the particulate were considered of a respirable size (<7m in aerodynamic diameter).
No. of animals per sex per dose:
Control animals:
Details on study design:
The substance was hand ground with a pestle and mortar prior to use.
A smple of the processed test substance was packed inteo the container of the Wright Dust Feed mechanism (WDF) using a hydraulic bench press to assist packing. An even desnity of the test substance was achieved by packing the container on stafes and applying a force of 2.5 ton to compress the powder. The applied force was sufficiente to prevent disintegration of the packed powder during the generation procedure. The packed container was weighed.
A supply of cleam dry air was connected to the generator and the supply pressure was adjusted to give a flow rate of 25 litres/minute, measured at the generator oulet. A neutralised diluent air supply, adjusted to give 10 litres/minute, was connected to the elutriator to provide a total air supply of 25 litres/minute.
The neutralised air supply was also passed externally over the elutriator to aid the removal of any electrostatic charge.
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 WDF was positioned horizontally on a stand at the side of the exposure chamber and the output was connected to the top inlet port of the chamber via the elutriation column. A speed controller setting of ‘70% of the maximum speed’ of the WDF was selected, as a result of preliminary generation trials, to generate a concentration of total particulate at the target concentration of 5 mg/l.
Each animal was placed into a separate restraining tube and the tubes were then attached to the exposure chamber.
The powder container of the WDF was advanced manually until a trace o suspended dust was seen to emerge from de WDF outlet. The gearing on the generator was then engaged and the generator motor switched to start the exposure.
After an equilibration period of 3 minutes, the exposure was timed for 4 hours. The WDF canister was replaced with further packed canisters as required during the exposure. The generator was then switched off and the chamber was allowed to clear before the animals were removed for examination.
Following exposure, the animals were returned to the holding cages where food and water were available. The test animals were kept in a ventilated cabinet overnight and then returned to the holding room for the remainder of the observation period.
The control group was treated similarly but received clean air only for 4-hours. The control animals were returned to the holding room at the end of the exposure period.


At the end of the 14-day observation period, the animals were killed by intraperitoneal injection of pentobarbitone sodium followed by exanguination from the brachial blood vessels.
All animals were subjected to a detailed macroscopic examination. The lungs (including the larynx and trachea) were removed, dissected clear of surrounding tissue, weighed and the weights recorded.
Lungs were discarded following necropsy.

Results and discussion

Preliminary study:
not applicable
Effect levels
Dose descriptor:
Effect level:
5 450 mg/m³ air
Exp. duration:
4 h
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 observed in all test rats immediately post exposure, persisting to Day 4 of the
Body weight:
A slightly reduced mean bodyweight 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.
Bodyweight gain values of the female test rats were similar to that of the control values.

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Migrated information
The LC50 (4-hour) for Nb2O5 NIOBIUM PENTOXIDE GRADE LN is in excess of 5.45 mg/l in air.