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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Experimental start date: 27th February Experimental completion date: 22nd 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
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

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

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
Yes - Study Plan Amendment No. 1: Change of study director and deputy
Principles of method if other than guideline:
ANIMAL WELFARE: This study was performed in an AAALAC-approved laboratory in accordance with the Swiss Animal Protection Law under license no. 34.
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 HanRcc WIST (SPF)
Strain:
other: See above
Sex:
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: 11 weeks when treated
- Weight at study initiation: No details provided in report
- Fasting period before study: The animals received a single dose of the test item by oral gavage administration at 2000 mg/kg body weight after being fasted for approximately 18 to 19 hours (access to water was permitted). Food was provided again approximately 3 hours after dosing.
- Housing: In groups of three per sex in Makrolon type-4 cages with wire mesh tops and standard softwood bedding (‘Lignocel’ Schill AG, CH-4132 Muttenz/Switzerland).
- 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 Iibitum. Results of bacteriological, chemical and contaminant analyses are archived at RCC Ltd.
- Acclimation period: 27th February 2007 – 5th March 2007 (females, 2000 mg/kg); 1st March 2007 – 7th March 2007 (females, 2000 mg/kg). Under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Standard Laboratory Conditions. 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

Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle:
- Amount of vehicle (if gavage):
- Justification for choice of vehicle: Olive oil was found to be a suitable vehicle. The vehicle was chosen after a non-GLP solubility trial which was performed before the study initiation date. This formulation trial is excluded from the GLP statement of compliance.
- Lot/batch no. (if required): Batch number: 47468174
- Purity: No details provided in report

MAXIMUM DOSE VOLUME APPLIED:

DOSAGE PREPARATION (if unusual): Dose levels are in terms of the test item as supplied by the sponsor. The dose formulations were made shortly before each dosing occasion using a magnetic stirrer, a spatula and an Ultra-Turrax (Janke & Kunkel, D-79219 Staufen) as homogenizers. The test item was weighed into a tared glass beaker on a suitable precision balance and the vehicle added (weight:volume). Homogeneity of the test item in the vehicle was maintained during administration using a magnetic stirrer.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:
Doses:
2000mg/kg body weight
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days (or other?):
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.

- Frequency of observations and weighing:
- Necropsy of survivors performed: yes/no
- Other examinations performed (clinical signs, body weight, organ weights, histopathology, other): 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.

VEHICLE:
Description: Yellowish oily liquid
Source: Carl Roth GmbH & Co. D-761 85 Karlsruhe/Germany Stability of vehicle: Stable under storage conditions;
Expiration date: 30-AUG-2007
Storage conditions: At room temperature (range of 20±3°C), light protected.
Safety precautions: Routine hygienic procedures were used to ensure the health and safety of the personnel.
Statistics:
No statistical analysis was used

Results and discussion

Preliminary study:
No deaths of the rats.
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: The median lethal dose of FP-100 after single oral administration to female rats, observed over a period of 14 days.
Mortality:
Female: 2000 mg/kg bw; Number of animals: 6; Number of deaths: 0
No deaths occurred during the study
Clinical signs:
All the animals showed a slightly ruffled fur which was present in the first three treated animals approximately 20 minutes after treatment up to the 5-hour reading and in the other three further animals from the 1-or 2-hour reading to the 5 hours post-dose.

In the first group this lasted from 20 minutes to the 5 hour
reading.

In the second group from 1 hour to 5 hour reading.
Body weight:
The body weight of the animals was within the range commonly recorded for this strain and age.
Gross pathology:
Effects on organs:
No abmornalities were observed.
Other findings:
No macroscopic findings were recorded at necropsy.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Executive summary:

Two groups, each of three female HanRcc:WIST (SPF) rats, were treated with FP-100 by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was diluted in vehicle (olive oil) at a concentration of 0.2 g/mL and administered at a dosing volume of 10 mL/kg.

 

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

 

All animals survived until the end of the study period.

All the animals showed a slightly ruffled fur which was present in the first three treated animals approximately 20 minutes after treatment up to the 5-hour reading and in the other three further animals from the 1-or 2-hour reading to the 5 hours post-dose.

The body weight of the animals was within the range commonly recorded for this strain and age.

 

No macroscopic findings were recorded at necropsy.