Registration Dossier

Toxicological information

Skin irritation / corrosion

Currently viewing:

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
26 September 2000 - 29 September 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report Date:
2000

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
Ta2O5
Tantalum Pentoxide Grade LT

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan UK Ltd., Bicester, Oxon, England
- Age at study initiation: at least 12 weeks
- Weight at study initiation: 2.4 – 2.9kg
- Housing: They were housed individually in stainless steel cages with perforated floors.
- Diet (e.g. ad libitum): ad libitum. A standard laboratory rabbit diet (Special Diet Services STANRAB (P) SQC pellet) was provided.
- Water (e.g. ad libitum): ad libitum. The water supplied to Huntingdon Life Sciences by Anglian Water was potable water for human consumption. Anglian Water takes its guidelines on water quality from the EEC directive relating to water for human consumption (80/778/EEC) and conforms to the United Kingdom Water Act 1989 and subsequent amendments. Results of routine physical and chemical examination of drinking water at consumers' taps, as conducted by the supplier, are made available to Huntingdon Life Sciences Ltd. as quarterly summaries.
- Acclimation period: 12 days
The batch of diet used for the study was analysed by the supplier for nutrients, possible contaminants and micro-organisms likely to be present in the diet and which, if in excess of specified amounts, might have an undesirable effect on the test system. The animals were fed hay on arrival and subsequently three times a week.
During the acclimatisation and study period the animals were given small (approximately 5 cm x 2 cm x 2 cm) soft white untreated wood blocks for environmental enrichment.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 ± 2 °C
- Humidity (%): 30 to 70 % relative
- Photoperiod (hrs dark / hrs light): 12 hours of artificial light (0600 - 1800 hours) in each 24-hour period.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
no
Amount / concentration applied:
The substance was moistened with 0.5 mL distilled water.
Duration of treatment / exposure:
4 h
Observation period:
1 h after treatment then daily for 72 h
Number of animals:
3
Details on study design:
TREATMENT PROCEDURE
Approximately 24 hours prior to application of the test substance, hair was removed with electric clippers from the dorso-lumbar region of each rabbit exposing an area of skin approximately 100 mm x 100 mm.
Approximately 0.5 g of the test substance was applied under a 2-ply 25 mm x 25 mm porous gauze pad, which had been moistened with 0.5 mL distilled water, to one intact skin site on each animal.
Each treatment site was covered with elastic adhesive dressing for four hours. The animals were not restrained during the exposure period and were returned to their cages immediately after treatment.
At the end of the exposure period, the semi-occlusive dressing and gauze pad were removed and the treatment site was washed with warm water (36°C) to remove any residual test substance. The treated area was blotted dry with absorbent paper.

OBSERVATIONS
Clinical signs:
All animals were observed daily for signs of ill health or toxicity.

Dermal responses:
Examination of the treated skin was made on Day 1 (i.e. approximately 60 minutes after removal of the dressings) and on Days 2, 3 and 4 (equivalent to approximately 24, 48 and 72 hours after exposure).

Local dermal irritation was assessed using the prescribed numerical system:

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) or eschar formation (injuries in depth) preventing erythema reading 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 (edges raised approximately 1 millimetre) 3
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure) 4

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: Mean overall score for 1, 24, 48 and 72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: Mean overall score for 1, 24, 48 and 72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
No dermal irritation was observed following a single semi-occlusive application of Ta2O5 Tantalum Pentoxide Grade LT to intact rabbit skin for four hours.
Other effects:
There were no signs of toxicity or ill health in any rabbit during the observation period.

Any other information on results incl. tables

No dermal irritation was observed following a single semi-occlusive application of Ta2O5 to intact rabbit skin for four hours.

 

The means of scores for these reactions at approximately 24, 48 and 72 hours after administration, calculated separately for each animal, are summarised below:

Table 1: Means of scores at approximately 24, 48 and 72 hours

Animal number

Erythema

Oedema

1378

0

0

1379

0

0

1380

0

0

EC trigger values*

≥2

≥2

* Classification is triggered if means of scores for either effect are 2 for two or three animals (or if effects persist to Day 14 in at least two animals).

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
No dermal irritation was observed following a single semi-occlusive application of Ta2O5 Tantalum Pentoxide Grade LT to intact rabbit skin for four hours.
Executive summary:

The irritation potential of the test material was examined in a dermal irritation study using New Zealand White rabbits. The study was performed to GLP standard and according to the following guidelines:

-EEC Methods for the determination of toxicity, Annex to Directive 92/69/EEC (Official Journal No. L383A, 29.12.92), Part B, Method B.4. Acute toxicity (Skin Irritation).

-OECD Guideline for Testing of Chemicals No. 404 "Acute Dermal Irritation/Corrosion". Adopted 17 July 1992.

-EPA Health Effects Test Guidelines OPPTS 870.2500 Acute Dermal Irritation EPA 712-C-98-196. August 1998.

No dermal irritation was observed following a single semi-occlusive application of the test material to intact rabbit skin for four hours.