Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 2008-09-03 to 2008-09-26
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well documented study performed according to OECD guideline 423 and EU method B.1 tris, in compliance with GLP. No deviations were noted.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: solid
Details on test material:
- Name of test material (as cited in study report): RT003186
- Substance type: no data
- Physical state: solid
- Analytical purity: 90%
- Impurities (identity and concentrations): no data
- Purity test date: no data
- Lot/batch No.: PFA 011
- Expiration date of the lot/batch: 2010-02-27 (retest date)
- Stability under test conditions: unknown in PEG 300; is excluded from the statement of compliance.
- Storage condition of test material: at room temperature (range of 20 +/- 5°C), light protected. Contact with water will be avoided.
-Stability of test item: stable under storage conditions

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: 6 female rats, HanRcc: WIST (SPF) from RCC Ltd, Laboratory Animal Services
- Age when treated: 11 weeks
- Weight when treated: 187.1 g - 202.1 g
- Fasting period before study: 17 to 17 1/2 hours prior to dosing, access to water was permitted. Food was provided again approx 3 hrs after dosing
- Housing: Standard Laboratory Conditions, in groups of three in Makrolon type-4 cages with wire-mesh tops and standard softwood bedding
- Diet (e.g. ad libitum): ad libitum, standard pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet
- Water (e.g. ad libitum): ad libitum, community tap water from Füllinsdorf
- Acclimation period: 6 days, under laboratory conditions, after health examinations. Only animals without any visible signs of illnes were used for the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12, automatically controlled, music during the daytime light period

IN-LIFE DATES: From: 2008-09-10 To: 2008-09-26

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Remarks:
PEG 300
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.2 g/ml
- Amount of vehicle (if gavage): 10 ml/kg body weight
- Justification for choice of vehicle: the vehicle was chosen after a non-GLP solubility trial which was performed before the study initiation date.
- Lot/batch no. (if required): 1349048
- Purity: no data
- Source: FLUKA Chemie GmbH, CH-9471 Buchs
- Stability of the vehicle: Stable under storage conditions
- Storage conditions: at room temperature (20 +/- 5°C), light protected

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg body weight

DOSAGE PREPARATION (if unusual):
- The dose formulations were made shortly before each dosing occasion using a magnetic stirrer and a spatula 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.
- Dose levels are in terms of the test item as supplied by the sponsor.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: no data
Doses:
2000 mg/kg
No. of animals per sex per dose:
3 females per group; 2 groups
Control animals:
no
Details on study design:
- Duration of observation period following administration: 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.
- Necropsy of survivors performed: yes, all 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.
Statistics:
No statistical analysis was used.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred during the study.
Clinical signs:
All animals showed ruffled fur at the 1- or 2-hour reading up to 5 hours after treatment, or up to test day 2. Hunched posture was noted in all animals 1 or 2 hours after treatment up to 5-hour reading or up to test day 2.
Body weight:
The body weight of the animals was within the range commonly recorded for this strain and ages.
Gross pathology:
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
Conclusions:
The median lethal dose of RT003186 after single oral administration to female rats, observed over a period of 14 days is:
LD50 (female rat): greater than 2000 mg/kg body weight.