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Toxicological information

Acute Toxicity: oral

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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:
other: GLP Guideline Study

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes
Test type:
acute toxic class method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): CPH, BAS 500 F - Stufe 100
- Physical state: solid
- Analytical purity: 99.1 %
- Lot/batch No.: 29486 / 2
- Stability under test conditions: The stability of the test substance has been proven by reanalysis.
- Storage condition of test material: Refrigerator, exclusion of light and oxygen (under nitrogen)

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 adult animals
- Weight at study initiation: animals of comparable weight; (150 g - 300 g) (+/- 20 % of the mean weight)
- Fasting period before study: at least 16 hours
- Housing: individually in stainless steel wire mesh cages, type DK-III
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 1 week


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

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: water with 0.5 % Tylose CB 30.000
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.25 g/100 ml and 2 g/100 ml
- Amount of vehicle (if gavage): 10 ml/kg
- Justification for choice of vehicle: aqueous formulation corresponds to the physiological medium

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: none given
Doses:
25 mg/kg, 200 mg/kg
No. of animals per sex per dose:
3 males and 3 females at 25 mg/kg, 3 females at 200 mg/kg
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
• Body weight determination: Individual body weights shortly before application (day 0), weekly thereafter and at the end of the study (before fasting period); additionally animals that died or were sacrificed moribund.
• Signs and symptoms: Recording of signs and symptoms several times on the day of administration, at least once each workday for the individual animals.
• Mortality: A check for any dead or moribund animal was made twice each workday and once on saturdays, sundays and on public holidays.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Statistics:
No statistics was performed

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 25 - < 200 mg/kg bw
Mortality:
0/3 males and 0/3 females died at 25 mg/kg, 2/3 females died at 200 mg/kg
Clinical signs:
no clinical signs were observed at 25 mg/kg, at 200 mg/kg the following clinical signs were observed: impaired general state (1/3), poor general general state (3/3), dyspnoea (3/3), abdominal position (3/3), anemic pallor (3/3), cyanosis (3/3), piloerection (1/1), discoloured urine (1/1) within 3 hours
Body weight:
males 25 mg/kg mean: day 0: 182 g, day 7: 262 g, day 13: 294 g
females 25 mg/kg mean: day 0: 180 g, day 7: 211 g, day 13: 225 g
females 200 mg/kg mean: day 0: 175 g, day 7: 202 g, day 13: 226 g
Gross pathology:
females at 200 mg/kg that died: Cyanosis, surviving female at 200 mg/kg: organs without particular findings
males and females at 25 mg/kg: organs without particular findings
Other findings:
no data

Applicant's summary and conclusion