Registration Dossier

Administrative data

acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference Type:
study report
Report Date:

Materials and methods

Test guidelineopen allclose all
according to
OECD Guideline 402 (Acute Dermal Toxicity)
according to
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
yes (incl. certificate)

Test material

Specific details on test material used for the study:
Identification: Frutonile
Description: Liquid
Batch Number: VE00002027 or 9000774502
Expiry Date: 19-Oct-2009
Storage conditions: At room temperature (range 20 +/- 5 °C, provided by Harlan Laboratories Ltd.), light protected.
Safety Precautions: Routine hygenic procedures (gloves, laboratory overall, goggles, fask mask). A full filtered, positive air-supplied respirator will be used during the inhalation process.

Test animals

Details on test animals and environmental conditions:
Animals: Rat, HsdHan: WIST (SPF)
Rationale: Recognized by international guidelines as recommended test system
Breeder: Harlan Laboratories B.V.
Number of Animals per grop: 5 males and 5 females
Age: Males (10 weeks), Females (12 weeks)
Body Weight range (when treated): 242.0 g - 281.5 g (females), 191.4 g - 220.8 g (males)
Identification: Unique cage number and corresponsing color-coded spots on the tail. The animals were marked at acclimatization start.
Randomization: Selected by hand at time of delivery. No computer generated randomization program.
Acclimatization: Under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.

Administration / exposure

Type of coverage:
corn oil
Details on dermal exposure:
One day before treatment, the backs of the animals were clipped with an electric clipper, exposing an area of approximately 10% of the total bosy surface. Only animals without injury or irritation to the skin were used in the test. On day one, the test item was applied at a dose of 2000 mg/kg body weight evenly on the intact skin with a syringe and covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage.
Application volume/kg body weight: 4 ml
Twenty-four hours after the application the dressing was removed and the skin was flushed with lukewarm tap water and drapped off with disposable paper towels. Thereafter, the reaction sites were assessed.
All animals were re-shaved on test days 8 and 15 to facilitate the reading of the local reactions
No. of animals per sex per dose:
5 animals per sex per dose
Control animals:
Details on study design:
Viability/Mortality: Daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15.
Clinical signs: Daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1 and twice daily during days 2-15.
Local dermal signs: Once daily during days 2 (following the dressing removal) through day 15 using the numerical scoring system.
Body Weights: On test days 1 (prior to administration), 8 and 15.
No statistical analysis was used

Results and discussion

Effect levels
Dose descriptor:
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
No deaths occured during the study
Clinical signs:
No clinical signs were observed during the course of the study
Body weight:
One female lost a negligible weight (0.2%) between treatment start and test day 8. The body weight of the animals was otherwise, within the range commonly recorded for the age and strain.
Gross pathology:
No macroscopic finding were recorded as necropsy.
Other findings:
Local dermal signs: Very slight erythema was observed in all 10 animals on test day 2 after the removal of the application patch and persisted up to test days 6 or 7. Thereafter, all animals were free of local signs up to test day 15, the end of observation time.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
The median lethal dose of Frutonile after single dermal administration of rats to both sexes, observed over a period of 14 days is:

LD50 (rat) : greater than 2000 mg/kg body weight

Based upon the classification criteria according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS), Second revised edition, 2007, Frutonile corresponds to Category 5.