Niobium dioxide

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2000-09-25 to 2001-03-20

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)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute 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

Details on test material:

- Name of test material (as cited in study report): Nb205 Niobium Pentoxide Grade LN
- Physical state: white powder
- Analytical purity: 99.99%
- Purity test date: 2000-08-22
- Lot/batch No.: 20000103
- Expiration date of the lot/batch: 2001-03-31
- Storage condition of test material: in the dark at ambient room temperature and in the original container

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK Limited, Margate, Kent, England
- Age at study initiation: 8-9 weeks
- Weight at study initiation: males: 259 - 298 g, females: 204 - 237 g
- Housing: in groups of 5/sex in stainless steel cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 9 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5 - 20.5
- Humidity (%): 39 - 68
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

clean air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: snout-only exposure chambers were of cylindrical form (30 cm diameter, 45 cm height)
- Exposure chamber volume: 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
- Source and rate of air: a supply of clean, dry air was connected to the generator and the supply pressure was adjusted to give a flow rate of 15 litres/minute, measured at the generator outlet.
- Method of conditioning air: 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. The test atmosphere was passed through a horizontal glass elutriator to reduce, by sedimentation, the amount of non-respirable particulate in the test atmosphere
- System of generating particulates/aerosols: a wright dust feed mechanism was used to produce the test atmosphere
- Method of particle size determination: two air samples were taken during the exposure at a sampling rate of 2 litres/minute using a Marple cascade impactor 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
- Treatment of exhaust air: the exhaust airflow was calibrated and adjusted to produce a slightly negative pressure
- Temperature, humidity, air chamber: 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 the exposure and then at 30 minutes intervals during the 4-hour exposure

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. Each air sample was withdrawn, at a rate of 2 litres/minute, through a pre-weighed glass fibre filter mounted in an open face filter holder. The volume of air sampled was measured using a wet-type gas meter. The filters were re-weighed following sampling for gravimetric analysis of the test aerosol
- Samples taken from breathing zone: no

TEST ATMOSPHERE (if not tabulated)
- MMAD: 3.3 µm, approximately 88% of the particulate were considered of respirable size (<7 µm in aerodynamic diameter)

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

Chamber concentration of Nb2O5:
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 µm and was within the acceptable range (1 µm to 4 µm) for an acute inhalation study. Approximately 88% of the particulate were considered of a respirable size (<7 µm in aerodynamic diameter).

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations:
Mortality: all cages were checked at least twice daily for dead or moribund animals
Clinical signs: animals were observed intermittently for signs of reaction during exposure and at least twice daily throughout the observation period
- Frequency of weighing: all animals were weighed 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
- Terminal studies: at the end of the observation period the animals were killed by i.p. injection of pentabarbitone sodium followed by exsanguination from the brachial blood vessels. All animals were subjected to 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.
- Other examinations performed: water consumption: a visual inspection of water bottles was conducted daily.

Statistics:

N.A.

Results and discussion

Preliminary study:

not applicable

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC0

Effect level:

> 5 450 mg/m³ air

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 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.

Gross pathology:

There were no treatment-related findings noted at necropsy

Other findings:

- Organ weights: no effects seen on lung weights
- Water consumption: no treatment-related effects were observed

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The LC0 (4-hour) for diniobium pentoxide is greater than 5.45 mg/L and therefore no classification is required according to CLP.

Executive summary:

In an acute inhalation toxicity study according to OECD Guideline 403, groups of young adult Sprague-Dawley rats (5/sex) were exposed via the inhalation route to niobium pentoxide (99.99 % purity) as aerosol in air for 4 hours nose only at the limit concentration of 5.45 mg/L. Animals then were observed for 14 days. No death occurred. Exaggerated breathing was observed in most test animals from the 1st hour and in all test rats from the 2nd hour of exposure. Exaggerated breath persisted until day 4 post exposure. Based on the results a LC₅₀ of greater than 5.45 mg/L can be considered for both sexes. Niobium pentoxide is not classified according to CLP.