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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:
guideline study

Data source

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

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
starting dose was 200 mg/kg
Principles of method if other than guideline:
References for test guidelines given in the study report:
EEC Directive 92/69, Publication No. L383A, B.1: Acute Toxicity-oral, December 29, 1992;
Acute toxic class method, A national validation study of the ATC Method - an alternative to the LD50 test, Arch. Toxicol. 66: 455-470, 1992
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
- Name of test material (as cited in study report): pyrazolon
- Physical state: crystalline powder, light-beige
- Analytical purity/Content: 100.5 g/ 100 g (H-NMR and IR spectroscopy)
- Lot/batch No.: 27967/95
- Storage condition of test material: room temperature, exclusion of light

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dr. K. Thomae GmbH, Biberach, Federal Republic of Germany
- Age at study initiation: young adults
- Weight at study initiation: animals of comparable weight; 150-300g (+/- 20% of the mean weight)
- Fasting period before study: at least 16 hours before administration
- Housing: single housing, stainless steel wire mesh cages
- Diet (e.g. ad libitum): ad libitum (Kliba labor diet 343, assayed for chemical and microbiological contaminants)
- Water (e.g. ad libitum): ad libitum (tap water, regularly assayed for chemical contaminants)
- Acclimation period: at least 1 week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24 °C (no deviations from these ranges which influenced the results of the study)
- Humidity (%): 30 - 70% (no deviations from these ranges which influenced the results of the study)
- Photoperiod (hrs dark / hrs light): 12/12


Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
VEHICLE
(cleaned natriumcarboxymethylcellulose in aqua bidest.)
- Concentration in vehicle: 2 g/100 ml and 20 g/100 ml
- Amount of vehicle (if gavage): 10 ml/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: based on the physical and chemical characteristics of the test substance
Doses:
200 and 2000 mg/kg bw
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:
clinical signs and symptoms: several times on the day of administration, at least once each workday;
mortality: twice each workday and once on Saturdays and Sundays;
body weights: d0 (shortly before application), weekly thereafter and at the end of the study (before fasting period)
- Necropsy of survivors performed: yes (withdrawl of food at least 16 hours before killing with CO2)

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortalities occured
Clinical signs:
200 mg/kg: no symptoms observed in males and females

2000 mg/kg:
all males showed an impaired or poor general state, dyspnoea, staggering and piloerection, 2/3 males showed apathy;
in female animals no abnormalities were observed
Body weight:
The expected body weight gain was observed in the course of the study, with the exception of one female animal of the 200 mg/kg dose group which showed weight reduction.
Gross pathology:
No findings

Applicant's summary and conclusion