Niobium oxide

Endpoint summary

Description of key information

Niobium oxide was tested negative in an acute skin and in an acute eye irritation/corrosion study (EU methods B.4 & B.5).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

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

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

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

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.

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

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.

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.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye 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

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, 97320 Sulzfeld, Germany
- Hygiene staus upon supply: SPF
- Weight at study initiation: 2268 - 3105 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: 2 - 4 weeks

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

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g

Duration of treatment / exposure:

single treatment, after 24 hours the treated eye was washed

Observation period (in vivo):

1, 24, 48 and 72 hours after instillation

Number of animals or in vitro replicates:

3 male rabbits

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): rinsing with deionised water
- Time after start of exposure: 24 h

SCORING SYSTEM: Draize method

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 instillation and persist for at least 24 hours in a test using three animals for classification of a substance as eye irritant and for the labelling with R36 (significant ocular lesions):
In at least two animals redness of conjunctivae ≥2.5, chemosis of conjunctivae ≥2.0, cornea opacity ≥2.0 < 3, iris lesion ≥1.0 < 2 and for labeling with R41 (severe ocular lesions) in at least two animals cornea opacity ≥3.0, iris lesions =2.0.
All responses scored at 24, 48 and 72 hours after instillation are used to calculate the mean value for each ocular lesion for each individual animal.
The classification as eye irritant and labelling with R41 (severe ocular lesions) is also necessary if a lower effect is not reversible in the 21 day observation period or an irreversible coloration of the cornea or iris are induced.

TOOL USED TO ASSESS SCORE: hand-slit lamp (Heine OPTOTECHNIK)

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of three animals

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Remarks:

of three animals

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

of three animals

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

of three animals

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

The control eyes of the animals showed no alterations at any observation time. A slight redness of the conjunctivae and a serous lacrimation was observed in all animals on the day of instillation. The cornea and iris were not affected. After 24 hours no signs of irritation were observed. For details on the individual results please see Table 1 in box "Any other information on results".

Other effects:

None of the animals died or showed clinical signs during the course of testing.

Table 1: Evaluation of alterations of eyes after instillation of niobium(II) oxide

Alteration	Animal No.	Observed grades of skin alterations of each observation time
		Hours after administration
		1		24		48		72
		Control	Test Item	Control	Test Item	Control	Test Item	Control	Test Item
Cornea	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
Iris	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
Conjunctivae Redness	1	0	1*	0	0*	0	0	0	0
	2	0	1*	0	0	0	0	0	0
	3	0	1*	0	0	0	0	0	0
Conjunctivae Chemosis	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

* serous lacrimation

Interpretation of results:

GHS criteria not met

Conclusions:

In conclusion, in a primary eye irritation study niobium oxide was instilled into the conjunctival sac of the eye of three young adult New Zealand White rabbits for 24 hours. Based on the results, niobium oxide can be considered as not eye irritating.

Executive summary:

In a primary eye irritation study (EU method B.5), 0.1 g of  niobium oxide (> 99% purity) was instilled into the conjunctival sac of the eye of three young adult New Zealand White rabbits for 24 hours. After the exposure period the treated eyes were rinsed with deionised water. Animals were observed for 1, 24, 48 and 72 hours after instillation. Irritation was scored by the method of Draize. In this study, none of the animals died or showed clinical signs of toxicity. A slight redness of the conjunctivae and a serous lacrimation was observed in all animals on the day of instillation. The cornea and iris were not affected. After 24 hours no signs of irritation were observed anymore. Based on the results, niobium oxide is not an eye irritant to the eye.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The target substance niobium oxide (>99% purity) was tested negative for acute dermal irritating properties in a study conducted according to EU method B.4. After a dermal exposure period of 4 hours no skin effects were observed in rabbits.

In an acute eye irritation study (EU method B.5) a slight redness of the conjunctivae and a serous lacrimation was observed in all animals on the day of instillation after treatment with the target substance. The cornea and iris were not affected. After 24 hours no signs of irritation were observed anymore. Based on the results, niobium oxide is not an eye irritant to the eye.

Justification for classification or non-classification

Based on the available data and according to regulation (EC) No. 1272/2008, no classification of niobium oxide for skin and eye irritation is warranted.