Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2005
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Report was translated from a Japanese report. Not all information is translated properly.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
other: Draize J.H., Woodard G & Clavery H.Q. (1944).
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rabbit
Strain:
other: Kbs:JW
Details on test animals and environmental conditions:
Female.
18 - 19 weeks old.

Breeding conditions:
Breeding room: CV-4 breeding room
Temperature: 22 +- 2 °C;
Humidity: 55 +- 20%;
Lighting: light and dark alternated for 12 h, lights on at 7:30 am, lights out 7:30 pm;
Ventilation No.: more than 15 times/h;
Feeding frequency: Once/day;
Microorganism level: Conventional level for breeding animals;

Housing cage:
Name: Aluminium hanging cage;
Size: 350 W x 500D x 345H (mm);
Floor cover: not used;

Diet:
Type: solid diet LRC-4 (Oriental Yeast);
Feeding method: at libitum;

Drinking water:
Type: Tap water specially installed at the Takasago Industry Institute, Kaneka (In accordance with the water standards of Takasago City).

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
physiological saline
Controls:
not specified
Amount / concentration applied:
500 mg
Duration of treatment / exposure:
4 hours
Observation period:
Evaluations were carried out 1, 24, 48 and 72 h after removal of specimen.
Observation of the general conditions were performed up to day 14.
Number of animals:
3 animals
Details on study design:
The hair on the back of the rabbits was shaved with an electric shaver the day before topical application. The back surface was divided into 2.5 x 2.5 cm sections and 6 areas for application were established on each individual animal. For VRT-753136 HCl (=T003110), 0.5 mL physiological saline was applied to gauze consisting of 16 superimposed pieces (2.5 x 2.5 cm) and 0.5 g of the test compound was applied to it respectivley, followed by attaching th gauze to the skin.
The attached gauze was covered with oilpaper and immobilized with tape and separate gauzes were used to wrap the areas and the chest and stomach areas as well, and the rabbits were immobilized for 4 h using cangue-type immobilizing devices. After immobilization, the specimen was washed with purified water and the areas were lightly wiped to cleanse the specimen from the areas of topical application.

Evaluations were carried out in accordance with the method of Draize e al. 1, 24, 48 and 72 h after the specimens were removed. The items for observation include erythema and scar and edema formation, which were observed with naked eye. Observation of the general conditions were performed up to day 14.

Method of evaluation:
The primary evalution values were calculated from the mean for each scoring point (erythema or scar formation or edema formation) at 1, 24, 48 and 72 h after the specimens were removed. Means were furthe obtained from the mean values of observation at each time point to give primary irritation index PII, which is an indicator for the degree of irritation.
The minimum value of PII is 0 and the maximum value is 8, and the values were classified into 4 classes, in that 0 was rated as no irritation, and in sequence, 2 was rated as being a weakly irritating substance, greater than 2 but less than 5 a moderate irritating substance and greater than 5 a profoundly irritating substance.

Body weight measurment:
Body weight was measured on the day of topical application, and on day 7 and day 14.

Results and discussion

In vivo

Results
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 72 h
Score:
0
Max. score:
0
Irritant / corrosive response data:
No erythema or edema was observed throughout the study period in the topical application of VRT-753136 HCl (T003110). Also, no abnormality was observed throught the study period with respect to the general condition and change of body weight.
The primary irritation index (PII value) calculated by Draize method was 0 for VRT-753136 HCl (T003110). VRT-753136 HCl (T003110) was classified as "non-irritating".
Other effects:
Throughout the entire study period no abnormality was observed in the general condition considered to be influenced by the topical application of the test substances.
No abnormality of the body weight was observed over time in any individual.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The substance VRT-753136 HCl (T003110) is consisdered as "non-irritating" in this skin irriation test according to OECD Guideline No. 404.