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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
09 May 2002 and 22 May 2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficincies, which do not affect the quality of relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Report date:
2002

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
Please see "Principles of method" for details.
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
Please see "Principles of method" for details.
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
yes
Remarks:
Please see "Principles of method" for details.
Principles of method if other than guideline:
The Study Protocol indicated that a suitably sized area of skin (dorso-Iumbar region) should be clipped free of hair on the day before administration, however, on the subject study two animals (numbers 33960 and 3962) were clipped two days before administration. Since the test and control sites of each animal were examined immediately prior to treatment and were found to be satisfactory, it is considered that this protocol deviation has had no impact on the study outcome.
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
Strontium titanium trioxide
EC Number:
235-044-1
EC Name:
Strontium titanium trioxide
Cas Number:
12060-59-2
Molecular formula:
O3Ti.Sr
IUPAC Name:
strontium titanium trioxide
Constituent 2
Reference substance name:
ST888YK
IUPAC Name:
ST888YK
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): ST888YK
- Physical state: White powder
- Lot/batch No.: 11423
- Expiration date of the lot/batch: March 2003
- Storage condition of test material: Room temperature

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Animals for this study were selected from a stock supply of healthy adult rabbits of the New Zealand White strain, obtained from Highgate Farm, Market Rasen, Lincolnshire, England.
They were in the weight range of 3.44 to 3.60 kg and at least eight weeks of age, prior to treatment (Day 1). All rabbits were acclimatised to the experimental environment for a period of at least 18 days prior to the start of the study.
The rabbits were selected without conscious bias for the study. They were housed individually in stainless steel cages with perforated floors at the Eye Research Centre, Eye, Suffolk, IP23 7PX.
A standard laboratory rabbit diet (Special Diet Services STANRAB (P) SQC pellet) and drinking water were provided ad libitum. 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 given a dietary supplement of hay.
During the acclimatisation and study period the animals were given small soft white untreated wood blocks for environmental enrichment.
Results of routine physical and chemical examination of drinking water, as conducted by the supplier are made available to Huntingdon Life Sciences Limited.
Animal room environmental controls were set to maintain temperature within the range 15 to 23°C, and relative humidity within 40 to 70%. These environmental parameters were recorded and the permanent record archived with other departmental raw data. Lighting was controlled by means of a time switch to give 12 hours of artificial light (06:00 to 18:00 GMT) in each 24 hour period.
Each animal was identified by a numbered tag placed through the edge of one ear. This identification was unique within the Department throughout the duration of the study. Each cage was identified by a coloured label displaying the study number, animal number, phase of study and initials of the Study Director and Home Office licensee.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
other: An additional skin site was similarly treated with the exception of test substance and acted as a control.
Amount / concentration applied:
TEST MATERIAL
The treatment site was 'wetted' with 0.5mL of reverse osmosis water and approximately 0.5 g of the test substance was applied under a 2-ply 25 mm x 25 mm porous gauze pad to intact skin sites
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
Three
Details on study design:
TEST SITE
On the day before application of the test substance, hair was removed with clippers from the dorso-lumbar region of each rabbit exposing an appropriate sized area of skin.
The treatment site was 'wetted' with 0.5mL of reverse osmosis water and approximately 0.5 g of the test substance was applied under a 2-ply 25 mm x 25 mm porous gauze pad to intact skin sites on three animals. An additional site was similarly treated with the exception of test substance and acted as a control.
A single animal received three exposures (of three minutes, one or four hours duration) in a step-wise manner and acted as a preliminary screen. In the absence of a severe effect on removal of the dressings the next exposure was initiated.
For exposures of one hour or more each treatment site was covered with "Tubigrip" elasticated bandage dressing for the duration of the exposure period. The animals were returned to their cages immediately after treatment.

REMOVAL OF TEST SUBSTANCE
At the end of the exposure period the semi-occlusive dressing and gauze pad were removed and the treatment site was washed with luke warm water (30-40°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 removal of the dressings (for 3 minute or one hour exposures) and approximately 1, 24, 48 and 72 hours later. Only the data for the four hour exposure are reported, the data from the three minute and one hour exposures are held in the archives.

SCORING SYSTEM:
Local dermal irritation was assessed using the prescribed numerical system detailed in "any other information on materials and methods" below.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
3945 (male)
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: No effects noted.
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
3960 (male)
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: No effects noted.
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
3962 (male)
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: No effects noted.
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
3945 (male)
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: No effects noted.
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
3960 (male)
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: No effects noted.
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
3962 (male)
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: No effects noted.
Irritant / corrosive response data:
No dermal irritation was observed in any animal throughout the duration ofthe study.
Other effects:
CLINICAL SIGNS
There was no sign of toxicity or ill health in any rabbit during the observation period.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The Primary Irritation Index (PII) was calculated to be 0.0 and ST888YK was classified as "non irritant" in accordance with the criteria of ECETOC.
The test material is not considered to be classified as irritating to skin according to Regulation (EC) No 1272/2008.
Executive summary:

A study was performed to assess the skin irritation potential of ST888YK to the rabbit. The method followed was that described in:

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-98196. August 1998.

Three rabbits received a single four hour, semi-occlusive, dermal administration of approximately 0.5 g of the test substance as supplied and were observed for four days.

No dermal irritation was observed in any animal throughout the duration of the study.

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

Means of scores at approximately 24, 48 and 72 hours

Animal number

Erythema

Oedema

3945

0.0

0.0

3960

0.0

0.0

3962

0.0

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).

The Primary Irritation Index (PII) was calculated to be 0.0 and ST888YK was classified as "non irritant" in accordance with the criteria of ECETOC.

The test material is not considered to be classified as irritating to skin according to Regulation (EC) No 1272/2008.

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