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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
12 to 28 November 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in accordance with OECD test guideline in compliance with GLP and reported with a valid GLP certificate.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified
Details on test material:
Identification: DUSANTOX 86, Certificate of analysis No. 040707/A9Batch number: 005/07Storage conditions: The test article was maintained in a dark package, in the room No. 252 (at room temperature) of the Toxicology and Pathology Dept, where was prepared for the administration. Long term storage: protected against sunlight. Stable: for 24 months.

Test animals

Species:
rabbit
Strain:
other: Albino, not specified
Details on test animals and environmental conditions:
Species: Albino rabbitSource: VŰŽV Nitra, SlovakiaNumber and sex: Four healthy young adult animals (males), weighing from 3,63kg to 4,62kgIdentification: The animals were housed individually in cages. The animals were marked by serial numbers 1 – 4. These numbers were placed in the cage and on the auricle. Husbandry:Housing: Animals were housed in cages individually. Diet: A standard certified laboratory diet (supplier Top Dovo Dobrá Voda) was served. The diet is routinely analysed by the manufacturer for nutritional components and environmental contaminants. Water: Ad libitum.Environment: Environmental control for the animal room was set to maintain 18 ± 3°C, a relative humidity of 40 – 70% a minimu of 10 air changes/hour, and a natural light regime. Acclimation: According SOP No 001/53204/07 Quarantine of animals.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
other: Olivae oleum raffinatum
Controls:
no
Amount / concentration applied:
A dose of 0.5 g of Dusantox 86 was pulverised, moistened with the vehicle. Vehicle Article: Olivae oleum raffinatum, Certificate of analysis No 625/539/64/2007, Lot Number: L706203
Duration of treatment / exposure:
exposure period 4 hours.
Observation period:
72 hours.
Number of animals:
4 male rabbits.
Details on study design:
Preparation of dosesThe test article was pulverised and moistened sufficiently with olivae oleum shortly prior to administration. Test ProcedurePreparation of Test Area: Approximately 24h before the test, fur was removed from the test area by clipping from the dorsal area of the trunk of the animals. Only animal with healthy intact skin were used. Exposure of Animals: The study was begun with an initial test using one animal. The test article was applied to a small area (approximately 6 cm2) of skin and covered with a gauze patch. The patch was loosely held in contact with the skin by means of a suitable semi-occlusive dressing for the duration of the exposure period (4h). At the end of the exposure period, residual test preparation was removed using olivae oleum. Because a corrosive effect was not observed in initial test, the irritant response was confirmed using up to three additional animals simultaneously.Application of Test Article: The test article (0.5 g) was moistened sufficiently with olivae oleum and was applied to the skin and to the gauze patch.Observation of Animals: The appearance of skin reactions was observed and recorded at 1h, 24h, 48h and 72 h following removal of the patches. The skin reactions for erythema and oedema were described and graded according to the classification system for the application site at each time interval.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
other: Primary Irritation Index (PII)
Basis:
animal #1
Time point:
other: 24, 48 & 72 hours
Score:
0 - 1
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Irritation score: 0.33
Irritation parameter:
other: Primary Irritation Index (PII)
Basis:
animal #2
Time point:
other: 24, 48 & 72 hours
Score:
0 - 1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Irritation score: 0.5
Irritation parameter:
other: Primary Irritation Index (PII)
Basis:
animal #3
Time point:
other: 24, 48 & 72 hours
Score:
0 - 1
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Irritation score: 0.17
Irritation parameter:
other: Primary Irritation Index (PII)
Basis:
animal #4
Time point:
other: 24, 48 & 72 hours
Score:
0 - 2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: Irritation score: 0.67
Irritant / corrosive response data:
Because a corrosive effect was not observed in initial test, the irritant response was confirmed using up to three additional animals simultaneously.
Other effects:
The well-defined erythema classified as grad 2 was observed as the worst skin reaction on the Dusantox 86 only in one animal. Skin reactions on other animals were determined as grad 1 – very slight erythema. No observation of erythema or oedema was noted on the vehicle application site. During 7 days after removal of patches erythema had disappeared in all animals. No oedema was occurred in the course of study.

Any other information on results incl. tables

Table 3. Score of reaction – numerical grading for skin reaction

Animal No.

Weight (kg)

Date of application

Time observation after removal patches

Irritation scores Dusantox 86

Irritation Scores of each animalΣErythema + oedema : 6

Primary irritation index (PII)

h.

date

Erythema

Oedema

1

4.33

13.11.07

1

13.11.07

1

0

0.33

0.4

24

14.11.07

1

0

48

15.11.07

1

0

72

16.11.07

0

0

2

3.65

14.11.07

1

14.11.07

1

0

0.5

24

15.11.07

1

0

48

16.11.07

1

0

72

17.11.07

1

0

3

3.63

14.11.07

1

14.11.07

1

0

0.17

24

15.11.07

1

0

48

16.11.07

0

0

72

17.11.07

0

0

4

4.62

14.11.07

1

14.11.07

1-2

0

0.67

24

15.11.07

2

0

48

16.11.07

1

0

72

17.11.07

1

0

Response category

Negligible

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The Primary Irritation Index of Dusantox 86 for single exposure determined in this study was PII = 0.4. According to this value the test article belongs to response category “negligible”.
Executive summary:

The skin irritation potential of Dusantox 86 was tested in four albino rabbits. The test article was applied in a single dose to the clipped skin of experimental animals, each animal serving as its own control. A dose of 0.5 g of Dusantox 86 was pulverised, moistened with olivae oleum and applied to the intact skin of rabbits for 4 h under semi-occlusive dressings. The degree of irritation was read and scored at specified intervals (1 h, 24h, 48 h and 72h following removal of the patches) and was described to provide a complete evaluation of the effects. The Primary Irritation Index of Dusantox 86 for single exposure determined in this study was PII = 0.4. According to this value the test article belongs to response category “Negligible”.

No classification and labelling is applicable.