Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
28 October 1997 - 20 November 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The acute oral toxicity study was conducted according to EU Method B.1 and OECD Guideline Method 423 without deviations and GLP practices.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report Date:
1998

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 423 (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:
solid - liquid: suspension
Details on test material:
- Name of test material (as cited in study report): Epyrrol
- Substance type: pure active substance
- Physical state: Powder, off white in color
- Composition of test material, percentage of components: Main component= 75%, other= 18%, other= 7%
- Lot/batch No.: GL-1291 K1
- Expiration date of the lot/batch: 24 September 1998
- Stability under test conditions: Not indicated
- Storage condition of test material: Stable at room temperature in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, Sulzfeld, Germany
- Age at study initiation: 9-10 weeks old
- Weight at study initiation: Body weight variation did not exceed +/- 20% of the sex mean.
- Fasting period before study: Food was withheld overnight prior to dosing until approximately 3-4 hours after treatment of the test substance
- Housing: Group house of 3 animals per sex per cage in labelled polycarbonatge cages
- Diet (e.g. ad libitum): Standard pelleted laboratory diet (from Carfil Quality BVBA, Oud-Turnout, Belgium), Ad libitum
- Water (e.g. ad libitum): Tap-water, ad libitum
- Acclimation period: At least 5 days before the start of treatment under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 deg C
- Humidity (%): 50%
- Air changes (per hr): 15 air changes/hour
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: Not documented in the report To: Not documented in the report

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
propylene glycol
Details on oral exposure:
DOSAGE PREPARATION (if unusual): The formulations (w/w) were prepared immediately prior to dosing. Adjustment was made for specific gravity of the vehicle. The concentration of the test sustance in vehile was varied to allow constant dosage volume in terms of ml/kg body weight. Homogeneity was accomplished to a visually acceptable level.
Doses:
2000 mg/kg bw, 200 mg/kg bw, and 25 mg/kg bw
No. of animals per sex per dose:
3/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality/Viability was observed twice daily; body weights were recorded on Day 1 (pre-administration, 8 and 15 and at death (if found dead after Day 1); Clinical signs were periodically observed on the day of dosing (Day 1) and once daily thereafter, until Day 15 (the time of onset, degree and duration were recorded and the symptoms graded according to fixed scales: Max grade 4= drading slight (1) to very severe (4), Max grade 3= drading slight (1) to severe (3), Max grade 1= presence is scored (1)).
- Necropsy of survivors performed: yes, at the end of the observation period, all animals were sacrificed by asphyxiation using a oxygen/carbon dioxide procedure and subject to necropsy.
Statistics:
None

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
25 - 200 mg/kg bw
Based on:
test mat.
Mortality:
All animals dosed at 2000 or at 200 mg/kg were found dead on day 2 or day 3, respectively. The surviving animals had recovered from the symptoms by day 2.
Clinical signs:
Clinical signs observed during the study period were as follows:
25 mg/kg: Uncoordinated movements (females only)
200 mg/kg: Lethargy, hunched posture, uncoordinated movements and piloerection.
2000 mg/kg: Lethargy, tremors, uncoordinated movements and ptosis of the eyes.
Body weight:
Body weight gain shown by the animals over the study period was considered to be normal.
Gross pathology:
Yellowish discoloration of all adipose tissue and reddish watery fluid in the thoracic and/or abdominal cavity were found in the 200 mg/kg treated animals at macroscopic post mortem examination. No abnormalities were found in the other dose groups.

Any other information on results incl. tables

Inadvertently, no animals observations were performed on Day 11 (males) and on Day 13 (females) of the 25 mg/kg dose group. Based on the previous observation, it was considered that this evernt has not adversely effected the study integrity.

Applicant's summary and conclusion

Interpretation of results:
toxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Oral LD50 value of Epyrrol in Wistar rats was established to be within the range of 25-200 mg/kg body weight.