Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April - July 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP, Guideline study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003

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
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Appearance: off-white crystals.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Sex: female.
Number: three animals were required for the complete test.
ldentification: animals were individually idcntified by an ear clip.
Body weight: individuai body weights were taken at the beginning and at the end of the experiment; generally between 2 kg and 3.5 kg at the start of the experiment.
Acclimatisation: for at least 5 days before the treatment, in the area where the experiment took place.
Housing: animals were housed individually in cages of standard size. Excreta was removed by unrolling plasticised brown paper, previously placed under cages. These cages were placed in an air conditioned (17- 21 °C) animal house kept at between 45 % and 65 % relative humidity in which non-recycled filtered air was changed approximately ten times per hour. The artificial day/night cycle was 12 hours light and 12 hours darkness with Iight on at 7.30 a.m.
Feeding: SAFE 112 feed was available ad libitum. The batch used was not quality controlled, therefore no certificate of analysis were available but only a data sheet concerning this feed product was included in report.
Drinking water: potable water was available ad libitum in polycarbonate feeder bottles with a stainless steel nipple. A specimen of water was obtained every 6 months and sent to the Laboratoire Départemental d'Analyse du Cher- 216 rue Louis Mallet, 18014 Bourges Cedex, France- for analysis.
The criteria for acceptable levels of contaminants in the water supply was within the limits of the analytical specifications.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: Each application were sufficiently moistened with distilled watcr or any other appropriate vehicle (generally 0.5 mL).
Controls:
other: Adjacent surfaces of non-treated skin of each animal were serve as a control for the trial.
Amount / concentration applied:
0.5 g of FEX0-07 were applied, as required by the guideline.
Duration of treatment / exposure:
Each animals received one patch for an exposure period of 4 hours; the substance was applied once only.
Observation period:
One hour, 24 hours, 48 hours and 72 hours approximately after removal of the dressing, any skin lesions, which may have developed on the right flank of each animal were evaluated.
With the Sponsor's agreement, additional monitoring may be continued to D8 if signs of initation persist al 72 hours and even D15 if they persist at D8.
(These additional observations were not normally continue for more than 14 days after treatment).
Number of animals:
3

The study were started using three animals. Justification of the number of animals per group: the number of animals per group is the minimum
number crabling an accurate assessment of the studied toxicological effect.
Details on study design:
The aim of the study was to determine in the rabbit irritant properties and/or degree of corrosion caused by FEX0-07 following a single, semi-occluded application to intact skin.
Dermal initation and/or corrosion was evaluated by grading of any skin initation reactions seen, using a predetermined scoring system.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: Mean indices were calculated from results obtained from each rabbit at times 24, 48 and 72 hours
Score:
0
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: Mean indices were calculated from results obtained from each rabbit at times 24, 48 and 72 hours
Score:
0
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: Mean indices were calculated from results obtained from each rabbit at times 24, 48 and 72 hours
Score:
0
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: Mean indices were calculated from results obtained from each rabbit at times 24, 48 and 72 hours
Score:
0
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: Mean indices were calculated from results obtained from each rabbit at times 24, 48 and 72 hours
Score:
0
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: Mean indices were calculated from results obtained from each rabbit at times 24, 48 and 72 hours
Score:
0
Irritant / corrosive response data:
Mean indices were calculated from results obtained far each rabbit at times 24 hours, 48 hours and 72 hours. For each parameter, the mean of indices for each rabbit for the three times (Mean index per parameter, per animal for the three times = Mi) was noted.
Erythema score: 0 (mean for the three tested animals and three trials)
Edema score: 0 (mean for the three tested animals and three trials).
Other effects:
no data

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the experimental conditions adopted, FEXO- 07 was found to be non-irritant for the skin of the Rabbit.
Executive summary:

Any irritant properties and/or degree of corrosion of FEXO-07 were evaluated in the Rabbit following a single semi-occluded application to intact skin, in compliance with requirements of OECD Guideline N. 404 and Method B4 of Council Directive N. 67/548/EEC and subsequent amendments.

3 animals were used for the study. 0.5 g of FEXO-07 was applied on the skin. Adjacent surfaces of untreated skin served as a control for the t:rial. Semi-occlusive dressings held the test substance in piace 4 hours on the skin of the three animals. Any cutaneous lesions were evaluated approximately one hour, 24, 48 and 72 hours, after removal of the dressing. The application of the test substance did not induce coloration of the application site and did not interfere with grading of any skin lesions. Mean indices were calculated from results obtained from each rabbit at times 24, 48 and 72 hours.

Results obtained were: Mean index (Mi) for Erythema and Oedema for each animal tested was 0.00.

Under the experimental conditions adopted, FEXO- 07 (batch 1/03) was found to be non-irritant for the skin of the Rabbit.