Registration Dossier

Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Version / remarks:
July 1992
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
December 1992
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Test material form:
liquid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 4FP90
- Expiration date of the lot/batch: August 1996

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature, darkness

Test animals

Species:
rat
Strain:
Wistar
Remarks:
Shoe:WIST
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Tierzucht Schönwalde GmbH D-16352 Schönwalde
- Weight at study initiation: 131 - 173 g.
- Fasting period before study: 18 h prior dosing
- Housing: transparent polycarbonate cages (macrolone type III, floor area 810 cm2
- Diet: ad libitum, complete rodent diet "Altromin 1314"
- Water: ad libitum, domestic quality drinking water acidified with hydrochloric acid to pH 2.5 in order to prevent microbial growth
- Acclimation period: 7 day

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 3
- Humidity (%): 55 ± 15
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: sesame oil
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

Doses:
The study was initiated with a sighting study: One female rat was given 2000 mg/kg bw and two days later another rat was given
5000 mg/kg bw. Only slight signs of toxicity were observed in these rats.
On the basis of the results from the sighting study it was decided to carry out the main study with one group consisting of five male and five female rats given a dose of 5000 mg/kg bw. The dose volume administered was 10 mL/kg bw both in sighting and main study.
No. of animals per sex per dose:
5
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Each rat was observed 1, 3 and 6 hours after administration and thereafter daily for a period of 14 consecutive days. Body weight was recorded on days 0, 7 and 14.
- Necropsy of survivors performed: yes
All rats were killed by inhalation of C02 on day 14 and subjected to a gross necropsy examination.

Results and discussion

Preliminary study:
The animals included in the sighting study survived the treatment. The rats had a body weight loss on day 14. In animal 1 (2000 mg/kg bw) piloerection was observed 1, 3 and 6 hours after application as well as on days 1 to 4. A pinched abdomen was observed 3 and 6 hours after application. In animal 2 (5000 mg/kg bw) piloerection was observed 1, 3 and 6 hours after application as well as on days 1 to 3. This animal showed a pinched abdomen after 1, 3 and
6 hours and on day 1. The animal was depressed after 3 and 6 hours. The post martern inspection revealed no abnormalities.
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
None of the animals died after 5000 mg/kg bw in the main study.
Clinical signs:
Four male animals showed a pinched abdomen and piloerection 1, 3 and 6 hours after application. One animal was depressed and had pinched abdomen and piloerection 1 hour after application. This animal showed signs of coma after 3 hours and 6 hours after application laboured respiration was also seen in this animal.
From day 1 up to the end of the observation period all male rats showed normal appearance and behaviour. Exept one animal showed a pinched abdomen and piloerection on day 1 and piloerection only on day 2.
Body weight:
The rats had a normal body weight gain during the study period.
Gross pathology:
The gross necropsy of male and female rats revealed no abnormalities.

Applicant's summary and conclusion