Pregn-4-ene-3,20-dione, 21-(acetyloxy)-6-fluoro-11-hydroxy-16-methyl-, (6.alpha.,11.beta.,16.alpha.)-

Endpoint summary

Description of key information

The acute toxicity (LD50) of fluocortolone-A-acetate in rats is > 2000 mg/kg bw after oral administration (Stark and Amir, 1998) and after dermal application (Stark and Wick, 1998).

 

 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Aug to Sep 1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

22 March 1996

Deviations:

no

GLP compliance:

yes

Remarks:

- but a QA check was not performed

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Schering AG
- Females (if applicable) nulliparous and non-pregnant: [yes/no]
- Weight at study initiation: males: 103-117 g; females: 100-106 g
- Fasting period before study: ca. 17.5 to 19 h
- Housing: conventional
- Diet (e.g. ad libitum): pell. Altromin® ad libitum
- Water (e.g. ad libitum): demineralized acidified water, pH 2-3 ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-22
- Humidity (%): 52-64
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

other: 900 mg NaCl + 85 mg Myrj 53 ad 100 ml bidest water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION (if unusual): The formulation was prepared freshly on application day and the administrations were carried out within approximately 2 h.

Doses:

2000 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: on day 8 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No animal died after administration of 2000 mg/kg bw.

Clinical signs:

other: The administration of 2000 mgkg bw was tolerated without compound-related clinical findings.

Gross pathology:

Necropsy revealed no compound-related findings after 2000 mg/kg bw.

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The LD50 of the test item in male and female rats after a single i.g. administration is > 2000 mg/kg body weight.

Executive summary:

In an acute oral toxicity study according to OECD test guideline 423 (1996), groups of fasted, young adult Wistar rats (3/sex) were given a single oral dose of  Fluocortolone acetate (100% a.i.) in 900 mg NaCl + 85 mg Myrj 53 ad 100 ml bidest water at a dose 2000 mg/kg bw and observed for 14 days.

Oral LD50 Combined ≥ 2000 mg/kg bw

 

No Mortality nor clinical signs occurred in this limit test.

 

Fluocortolone is of low toxicity based on the LD50 in male and female Wistar rats.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

July 1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

24 February 1987

Deviations:

yes

Remarks:

3 instead of 5 animals/sex used

GLP compliance:

yes

Remarks:

- but a QA check was not performed

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Schering AG
- Weight at study initiation: males: 278-282 g; females: 204-207g
- Housing: individually under conventional conditions
- Diet (e.g. ad libitum): pell. Altromin® R ad libitum
- Water (e.g. ad libitum): demineralized acidified water, pH 2-3 ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 64-66
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Vehicle:

other: liquid paraffin

Details on dermal exposure:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):
step I: 556 and 564 mg ZK 47525 + 0.6 mL vehicle
step I: 556 mg ZK 47525 + 0.5 mL vehicle
step II: 408-414mg ZK 47525 + 0.5 mL vehicle

- For solids, paste formed: yes

Duration of exposure:

24 hours

Doses:

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: Day 1, 7 and 14
- Necropsy of survivors performed: yes
- Clinical signs including body weight: The comparison of the individual values revealed a decrease in body weight gain in male animals dosed with 2000 mg of the test item between day 1 and day 7 of the test. Two male animals (nos. 232; 234) showed even a body weight loss at this time-point. On day 14 the above-mentioned animals showed a body weight gain in the normal range wh ich was routinely observed in our laboratory. No compound-related findings were observed in body weight gain in female animals.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No animal died after administration of 2000 mg/kg bw.

Clinical signs:

other: A single dermal application of 2000 mg/kg was tolerated without compound-related findings.

Gross pathology:

Necropsy revealed no compound-related findings after 2000 mg/kg bw.

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The LD50 of ZK 47525 in male and female rats after a single dermal application is > 2000 mg/kg body weight. Local application was tolerated without irritation of the skin.

Executive summary:

In an acute dermal toxicity study according to OECD test guideline 402, groups of young adult Wistar rats (3/sex) were dermally exposed to Fluocortolone acetate (100% a.i) in liquid paraffin for 24 hours at a dose of 2000 mg/kg bw.  Animals then were observed for 14 days.

 

Dermal LD50 Combined ≥ 2000 mg/kg bw

 

No mortality nor clinical signs occurred in this limit test.

 

Fluocortolone acetate is of low Toxicity based on the LD50 value for male and female Wistar rats.

The single dermal administration of 2000 mg of the test item/kg was tolerated without compound-related clinical findings.

The comparison of the individual values revealed a decrease in body weight gain in male animals dosed with 2000 mg of the substance between day 1 and day 7 of the test. Two male animals (nos. 232; 234) showed even a body weight loss at this time-point. On day 14 the above-mentioned animals showed a body weight gain in the normal range which was routinely observed in our laboratory. No compound-related findings were observed in body weight gain in female animals.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Additional information

A single oral administration (gavage) of the test substance to male and female rats at the limit-dose 2000 mg/kg bw was tolerated without mortalities, clinical signs, effects on body weight gain and gross pathological findings (Stark and Amir, 1998). According to OECD TG 423 the oral LD50 of ZK 47525 (fluocortolone-A-acetate) in male and female rats is therefore > 2000 mg/kg bw.

A single dermal administration of the test substance to male and female rats at the limit-dose 2000 mg/kg was tolerated without mortalities, compound-related clinical findings, effects on body weight gain and gross pathological findings (Stark and Wick, 1998). According to OECD TG 402 the dermal LD50 of ZK 47525 (fluocortolone-A-acetate) in male and female rats is therefore > 2000 mg/kg bw.

Justification for classification or non-classification

Based on the study results a classification according to Regulation (EC) No. 1272/2008 (CLP) is not required.