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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Experimental start date: 27th February 2007 Experimental completion date: 20th March 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: - Study generated according to generally valid and/or internationally accepted testing guidelines - Performed according to GLP - Test parameters based on specific testing guideline

Data source

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

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
Study Plan Amendment No. 1: Change of study director and deputy
Principles of method if other than guideline:
Directive 92/69/EEC, B.3. ‘’Acute Toxicity-Dermal’’, July 31, 1992.

ANIMAL WELFARE: This study was performed in an AAALAC-approved laboratory in accordance with the Swiss Animal Protection Law under license no. 32.
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
- Name of test material (as cited in study report): FP-100
- Physical state: Solid, pale yellow
- Analytical purity: >99%
- Purity test date: No details provided in report
- Lot/batch No.: 060511
- Expiration date of the lot/batch: September 2007
- Storage condition of test material: At room temperature at about 20°C. Protection from light is desirable.
- Other: All test item handling was performed in the dark.

Test animals

Species:
other: rat (Wistar)
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd. Laboratory Animal Services CH-4414 Füllinsdorf/Switzerland
- Age at study initiation: Age when treated Males: 8 weeks, Females: 11 weeks
- Weight at study initiation: No details provided in report
- Fasting period before study: No details provided in report
- Housing: During acclimatization in groups of five per sex in Makrolon type-4 cages with standard softwood bedding. Individually in Makrolon type-3 cages with standard softwood bedding (“Lignocel”, Schill AG, CH-4132 Muttenz) during treatment and observation.
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 89/06 (Provimi Kliba AG, CH-4303 Kaiseraugst/ Switzerland) ad libitum. Results of analyses for contaminants are archived at RCC Ltd.
- Water (e.g. ad libitum): Community tap water from Füllinsdorf ad libitum. Results of bacteriological, chemical and contaminant analyses are archived at RCC Ltd.
- Acclimation period: 27th February 2007 – 5th March 2007. Acclimatisation: Under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
Standard laboratory conditions:
- Temperature (°C): continuously monitored environment with ranges for room temperature 22 ± 3°C
- Humidity (%): relative humidity between 30-70% (values above 70% during cleaning process possible)
- Air changes (per hr): Air-conditioned with 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): automatically controlled light cycle of 12 hours light and 12 hours dark, music during the daytime light period

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
olive oil
Details on dermal exposure:
TEST SITE
- Area of exposure: Back
- % coverage: 10
- Type of wrap if used: Semi-occlusive dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Skin was flushed with lukewarm tap water and dried with disposable paper towels. Thereafter, the reaction sites were assessed.
- Time after start of exposure: 24h after application

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Application volume/kg body weight: 4 ml
- Concentration (if solution):
- Constant volume or concentration used: yes
- For solids, paste formed: yes

Duration of exposure:
24 h
Doses:
On test day 1, 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.
No. of animals per sex per dose:
Number of animals per group: 5 males and 5 females
Total number of animals: 5 males and 5 females
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days (or other?): 14 days
- Frequency of observations and weighing:
Mortality/Viability: 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.
Body weights: On test days 1 (prior to administration), 8 and 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. Once daily during days 2-15. All abnormalities were recorded,
Local signs: Once daily during days 2-15. All abnormalities were recorded.
- Necropsy of survivors performed: Yes All surviving animals were killed at the end of the observation period by carbon dioxide asphyxiation and discarded after macroscopic examinations were performed. No organs or tissues were retained.
- Other examinations performed: clinical /local signs, body weights, macroscopic examinations
Statistics:
No statistical analysis was used

Results and discussion

Preliminary study:
See Below
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
act. ingr.
Mortality:
Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Clinical signs:
Signs of toxicity related to dose levels:
No signs of systemic toxicity observed.No clinical signs were evident in any animal during the acclimatisation period.

Nine animals showed a slight general erythema beginning at test day 2 and persisting as slight until test day 4. In one animal the slight general erythema was present from the 2-day reading and persisted until 6 days after treatment. This animal showed additionally crusts from test day 4 till test day 12.
Body weight:
One animal showed a slight loss of weight (1.9%) at day 8, the animal recovered until the end of the study. The body weight of the other animals was within the range commonly recorded for this strain and age.
Gross pathology:
Effects on organs:
There were no macroscopic abnormalities observed at time of autopsy.
Other findings:
Signs of toxicity (local):
No clinical signs were evident in any animal over the
test/observation period.


Erythema were present in all animals on days 2 through 4.


One animal (female) exhibited Erythema on days 2 through 6
and crusts on days 4 through 12.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The median lethal dose of FP-100 after single dermal administration to rats of both sexes, observed over a period of 14 days is:

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

Five male and five female HanRcc:WIST (SPF) rats were treated with FP-100 at 2000 mg/kg by dermal application. The test item was diluted in vehicle (olive oil) at a concentration of 0.5 g/mL and administered at a volume dosage of 4 mL/kg. The application period was 24 hours.

 

The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs at approximately 30 minutes, 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. Local signs were noted once daily from test day 2 to 15. Mortality/viability was recorded at approximately 30 minutes, 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.

 

No deaths occurred during the study.

 

Nine animals showed a slight erythema beginning at test day 2 after removal of the dressing and persisting as slight until test day 4. In one animal the slight general erythema was present from the 2-day reading and persisted until 6 days after treatment. This animal showed additionally crusts from test day 4 till test day 12.

One animal showed a slight loss of weight (1.9%) at day 8, the animal recovered until the end of the study. The body weight of the other animals was within the range commonly recorded for this strain and age

 

No macroscopic findings were observed at necropsy.