Registration Dossier

Toxicological information

Acute Toxicity: oral

Currently viewing:

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1973
Report Date:
1973

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not applicable
Remarks:
pre-guideline study
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

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): Difluocortolon-valerianat (ZK 22612)
- Lot/batch No.: not specified

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Tierzüchter Dr. Hagemann (not further specified)
- Age at study initiation: no data
- Weight at study initiation: 84 -117 g
- Fasting period before study: approx. 20 hours
- Housing: conventional (1 animal per cage)
- Diet (ad libitum): Altromin R
- Water (ad libitum): tap water
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.5 - 24.0
- Humidity (%): 50 - 63
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.9 g NaCl + 0.5 g CMC + 0.085 g Myrj ad 100 ml aqua dest.
Doses:
2000, 2500, 3000, 3500 and 4000 mg/kg bw
No. of animals per sex per dose:
5/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 39 days
- Kind of observations: clinical signs, mortality
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 100 mg/kg bw
Based on:
test mat.
95% CL:
>= 2 700 - <= 3 800
Mortality:
Mortality was observed at 2000 mg/kg bw and above in both sexes. Animals died between 5 and 22 days after application (details see Table 1).
Clinical signs:
After single oral administration animals of all dose levels showed emaciation from day 5 to day 39 of the observation period. At 2000 mg/kg bw and above ungroomed coat and apathy was observed. At 2500 mg/kg bw and above sporadic increased girth of abdomen as well as at 3000 mg/kg and above individual anaemic animals were seen.
Body weight:
Not examined
Gross pathology:
At necropsy perforating ulcers in the cutaneous stomach mucosa were observed in sacrificed animals at the end of the observation period (from 2500 mg/kg bw). In animals found dead perforating ulcers in the cutaneous stomach mucosa and splenic athropy (from 2000 mg/kg bw), hyperemia in the gastrointestinal tract and necrobiosis in the liver (from 2500 mg/kg bw) as well as petechial bleedings in the glandular stomach mucosa and anaemic renal infarction (from 3000 mg/kg bw) were recorded.

Any other information on results incl. tables

Table 1: Number of dead animals per dose group after single oral application of difluocortolon-valerinat (ZK 22612) to rats:

  Dose [mg/kg] No of dead males/
No of treated males 
No of dead females/
No of treated females  
 No of dead animals (total 39 days after admin.) /
No of treated animals  
 2000 3/5 2/5 5/10 
 2500 1/5 3/5 4/10 
 3000 3/5  4/5 7/10 
 3500 4/5 1/5 5/10 
 4000 2/5 4/5 6/10 

Applicant's summary and conclusion

Executive summary:

After single oral administration of the test item difluocortolon-valerianat (diflucortolone-21-valerate) in doses of 2000, 2500, 3000, 3500 and 4000 mg/kg bw to male and female rats (5/sex/group) clinical signs (emaciation, ungroomed coat , apathy, sporadic increased girth of abdomen, individual anaemic animals) were observed starting at 2000 mg/kg bw. Mortality was observed at 2000 mg/kg bw and above in both sexes. Animals died between 5 and 22 days after application. At necropsy perforating ulcers in the cutaneous stomach mucosa were observed in sacrificed animals at the end of the observation period (from 2500 mg/kg bw). In animals found dead perforating ulcers in the cutaneous stomach mucosa and splenic athropy (from 2000 mg/kg bw), hyperemia in the gastrointestinal tract and necrobiosis in the liver (from 2500 mg/kg bw) as well as petechial bleedings in the glandular stomach mucosa and anaemic renal infarction (from 3000 mg/kg bw) were recorded. The acute oral toxicity (LD50) of diflucortolone-21-valerate was determined to be 3100 mg/kg bw for male and female rats.