6 alpha-Fluoro-16 alpha-methyl-21-valeryloxy-1,4,9(11)-pregnatriene-3,20-dione

Acute Toxicity: oral

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:

1965

Report date:

1965

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

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

Test material information

Constituent 1

Reference substance name:

Fluocortolone

EC Number:

205-811-5

EC Name:

Fluocortolone

Cas Number:

152-97-6

Molecular formula:

C22H29FO4

IUPAC Name:

6-fluoro-11,21-dihydroxy-16-methylpregna-1,4-diene-3,20-dione

Details on test material:

- Name of test material (as cited in study report): fluocortolone (ZK 10445)

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Tierzüchter Wulf (not further specified)
- Age at study initiation: no data
- Weight at study initiation: 80-110 g
- Fasting period before study: 16- 18 hours
- Housing: conventional (1 animal per cage)
- Diet (ad libitum): Altromin R
- Water (ad libitum): tap water
- Acclimation period: 4-5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23
- Humidity (%): 55-65
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: gummi arabicum ad aqua dest.

Doses:

45, 125, 180, 250, 360, 500, 720 and 2000 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: 8 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:

245 mg/kg bw

Based on:

test mat.

95% CL:

>= 173 - <= 347

Mortality:

Animals of the dose level of 125 mg/kg bw and above died between 2 and 8 days after application (details see table 1).

Clinical signs:

other: After single oral administration animals developed apathy from 125 mg/kg upwards.

Gross pathology:

At autopsy, hydrops ascites and fibrinous peritonitis, changes in the gastrointestinal tract such as ulcers, erosions and thickening of the gastric mucous membrane were observed. Also haemorrhagic mesenteric lymph nodes, necrobiosis of the liver, abscesses and subacute pneumonia in the lungs were noted. Adhesions of organs contained in the abdominal cavity were found.

Any other information on results incl. tables

Table 1: Number of dead animals per dose group after single oral application of fluocortolone (ZK 10445) to rats (males and females combined):

Dose [mg/kg]	No of dead animals/ No of treated animals
50	0/10
125	3/10
180	5/10
250	7/10
360	7/10
500	8/10
720	8/10
2000	9/10

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The acute oral toxicity (LD50) of fluocortolone in male and female rats is 245 mg/kg.

Executive summary:

After single oral administration of fluocortolone in doses of 45, 125, 180, 250, 360, 500, 720 and 2000 mg/kg bw to male and female rats (5/sex/group) apathy was found as clinical sign. At autopsy, hydrops ascites and fibrinous peritonitis were observed. Furthermore changes in the gastrointestinal tract such as ulcers, erosions and thickening of the gastric mucous membrane were detected. Haemorrhagic mesenteric lymph nodes, necrobiosis of the liver, abscesses and subacute pneumonia in the lungs were noted. Adhesions of organs contained in the abdominal cavity were found. Animals of the dose level of 125 mg/kg bw and above died between 2 and 8 days after application. The acute oral toxicity (LD50) of fluocortolone in male and female rats is 245 mg/kg bw.