Niobium oxide

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2003-01-02 to 2003-03-20

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Niobium oxide

EC Number:

234-808-1

EC Name:

Niobium oxide

Cas Number:

12034-57-0

Molecular formula:

NbO

IUPAC Name:

niobium oxide

Test material form:

solid

Details on test material:

- Lot/batch No. of test material: SNB10OG200277M
- Expiration date of the lot/batch: 2003-12-31
- Purity: >99%
- Description: black, odourless powder
- Storage condition of test material: dry, room temperatue, closed container

Test animals

Species:

rabbit

Strain:

New Zealand White

Remarks:

Crl:NZW

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, 97320 Sulzfeld, Germany
- Hygiene status upon supply: SPF
- Weight at study initiation: 2800 - 3310 g
- Housing: Cages of stainless steel with bottom grid of oval steel and with tub for faeces, dimensions of cages: 50 x 55 x 40 cm
- Diet (e.g. ad libitum): ad libitum, ALTROMIN 2123, standard diet for rabbits
- Water (e.g. ad libitum): ad libitum, tap water
- Bedding: ALTROMIN Type S8/15, granulated soft wood bedding
- Acclimation period: 4 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 21
- Humidity (%): 30 - 40
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

other: 0.5% (m/v) solution of Tylose MH 1000 in deionised water

Controls:

yes, concurrent vehicle

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

VEHICLE
- Amount(s) applied (volume or weight with unit): test item was moistened
- Concentration (if solution): 0.5 % (m/v) Tylose MH 1000 in deionised water

NEGATIVE CONTROL
- Amount(s) applied (volume or weight): 0.5 mL of the vehicle 0.5% (m/v) Tylose MH 1000 in deionised water
- Concentration (if solution): 0.5% (m/v) Tylose MH 1000 in deionised water

Duration of treatment / exposure:

4 h

Observation period:

72 h

Number of animals:

3 male rabbits

Details on study design:

TEST SITE
- Area of exposure: 2 x 3 cm
- coverage: one layer of gauze patch (2.5 x 3.5 cm) and aluminium foil (3 x 4 cm)
- Type of wrap if used: occlusive (Elastoplast, Beiersdorf AG)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): rinsing with deionised water after patch removal
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS (indicate if minutes, hours or days)
1, 24, 48, and 72 h after patch removal

SCORING SYSTEM:
- Method of calculation:

Erythema and Eschar formation

No erythema 0
Very slight erythema (barely perceptible) 1
Well defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to eschar formation preventing
grading of erythema 4

Oedema formation

No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well defined by definite raising) 2
Moderate oedema (raised approx. 1 mm) 3
Severe oedema (raised more than 1 mm and extended beyond area
of exposure) 4

Evaluation criteria:

The evaluation of results was carried out according to Appendix 6 to Directive 2001/59/EU of August 06, 2001.
The following criteria should be fulfilled within 72 hours after patch removal in a test using three test animals for the classification of a substance as a skin irritant and for labelling with R 38:
In at least two animals Erythema and Eschar formation: ≥2.0 or Oedema formation: ≥2.0, which persist for at least 24 hours.
All responses scored at 24, 48 and 72 hours after patch removal are used to calculate the mean value for each skin lesion for each individual animal.
The same classification is necessary if a lower effect is not reversible within the 14 day observation period.

OTHER EXAMINATIONS:
- Body Weight: Body weights were recorded on the day of administration and at the end of the observation period
- Clinical observations and mortality: The animals were monitored for general clinical signs on the day of administration and once daily thereafter.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

The treated and also the control skin area did not show any irritations at any observation time. After one hour the administration area was discoloured slightly black in all animals. This discolouration did not interfere with the evaluation of a possible erythema.
For detailed information on the individual results, please see Table 1 in box "Any other information on results".

Other effects:

None of the animals died during the course of investigation and no clinical signs were observed.

Any other information on results incl. tables

Table 1: Evaluation of alterations of the skin area after administration of the test item

Alteration	Animal No.	Observed grades of skin alteratioons of each observation time
		Hours after administration
		1		24		48		72
		Control	Test Item	Control	Test Item	Control	Test Item	Control	Test Item
Erythema	1	0	0*	0	0*	0	0	0	0
	2	0	0*	0	0	0	0	0	0
	3	0	0*	0	0	0	0	0	0
Oedema	1	0	0	0	0	0	0	0	0
	2	0	0	0	0	0	0	0	0
	3	0	0	0	0	0	0	0	0

* The administration area was discoloured slight black; this discolouring did not interfere with the evaluation of a possible erythema.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In the acute dermal irritation/corrosion study according to Directive 67/548/EEC, Annex V, B.4, niobium oxide is considered to be non-irritating to the skin.

Executive summary:

In a primary dermal irritation study (EU method B.4), young adult male New Zealand White rabbits (3/sex) were dermally exposed to 0.5 g of niobium oxide (>99% purity), moistened with 0.5% (m/v) solution of Tylose MH100 in deionised water for 4 hours to a body surface area of 2 x 3 cm. Animals then were observed for 1, 24, 48 and 72 hours. Irritation was scored by the method of Draize.

Neither mortality nor any adverse clinical signs of toxicity were observed during the study. The treated and also the control skin areas did not show any irritations at any observation time. In this study, niobium oxide is not a dermal irritant.