Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1999-06-09 to 1999-07-13
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report Date:
2000

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
(1996)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
(1996)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Substance type: organic
- Physical state: liquid
- Analytical purity: 45 %
- Storage condition of test material: at room temperature

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Boehringer Ingelheim Pharma KG
- Age at study initiation: young adults
- Weight at study initiation: males: 172 - 184 g; females: 178 - 192 g
- Fasting period before study: 16 hours prior to treatment
- Housing: individually
- Diet: Kliba-Labordiaet, Provimi Kliba SA, Kaiseraugst, Switzerland, ad libitum
- Water: Tap water ad libitum
- Acclimation period: at least one week.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 2 and 5 g/100 mL

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

CLASS METHOD
- Rationale for the selection of the starting dose: Based on the physical and chemical characteristics of the test substance and the composition a starting dose of 500 mg/kg body weight has been chosen.
Doses:
200, 500 mg/kg
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 200 - <= 500 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 125 - <= 312 mg/kg bw
Based on:
act. ingr.
Remarks on result:
other: recalculated based on dye content of registered substance (72% w/w) versus tested material (45% w/w)
Mortality:
At 200 mg/kg bw no animal died. 1 male and one female died within the first day after the application in the high dose group. A second female deceased until day 5 after the application.
Clinical signs:
Clinical symptoms were more pronounced in females.
Males-200 mg/kg bw: Impaired general state, dyspnoea and piloerection in one animal disappeared within one day.
Males-500 mg/kg bw: Impaired general state, dyspnoea, piloerection, poor general state and apathy in three animals (piloerection: 2) disappeared at least within one day.
Females-200 mg/kg bw: Poor general state, dyspnoea, apathy, staggering and piloerection in one animal disappeared within one day.
Females-500 mg/kg bw: Impaired general state, dyspnoea, piloerection, poor general state and apathy in three animals (piloerection: 2) disappeared at least within one day.
Body weight:
All animals gained weight throughout the study period. Male animals showed a mean body weight of 282 to 288 g at the end of the study period. Females had a mean body weight of 211 to 220 g.
Gross pathology:
No gross internal lesions were observed in sacrificed animals. The animals that died during the study showed a discolouration of contents of the stomach and small and large intestines. One animal showed a discolouration of the adrenal glands.

Applicant's summary and conclusion