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Description of key information

The acute oral LD50 values of 16alpha-hydroxyprednisolone is higher than 2000 mg/kg bw.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed to GLP and OECD current guidelines
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
other: Hsd (SD) albino rats
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: well known breeder
- Age at study initiation: approximately eight to twelve weeks of age prior to dosing (Day 1)
- Weight at study initiation: 165 to 175 g
- Fasting period before study: overnight prior to and approximately four hours after dosing
- Housing: in groups of up to three rats, in solid bottomed polycarbonate cages with a stainless steel mesh lid. Each cage contained a quantity of autoclaved
wood flake bark-free fibre bedding
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 23°C
- Humidity (%): 40 to 70%
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 hours continuous light and 12 hours continuous dark

IN-LIFE DATES: From: 8 April 2013 To: 28 May 2013
Route of administration:
oral: gavage
Vehicle:
other: 1% w/v aqueous methyl cellulose
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 and 200 mg/mL
- Amount of vehicle (if gavage): 1% w/v aqueous methyl cellulose

MAXIMUM DOSE VOLUME APPLIED:10 mL/kg bodyweight

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The dose levels for the study were chosen in compliance with the study guidelines. As no previous toxicological information was available, the initial dose level was 300 mg/kg.
Doses:
300 and 2000 mg/kg bodyweight
No. of animals per sex per dose:
6 female rats dosed with 300 mg/kg bw
6 female rats dosed with 1000 mg/kg bw
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days, animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only).The weight of each rat was recorded on Days 1 (prior to dosing), 8 and 15.
- Necropsy of survivors performed: yes
- Macroscopic pathology: All animals were subject to a macroscopic examination which consisted of opening the cranial, thoracic and abdominal cavities. The macroscopic appearance of all examined organs was recorded.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths during the study
Clinical signs:
There were no signs of ill health, behavioural change or reaction to treatment observed throughout the study.
Body weight:
A low bodyweight gain was noted for one female (T1) on Day 15. All other animals were considered to have achieved satisfactory bodyweight gains throughout the study.
Gross pathology:
No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 15.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute median lethal oral dose (LD50) to rats of 16alpha-hydroxyprednisolone was demonstrated to be greater than 2000 mg/kg bodyweight.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Only study available for this endpoint with this substance. Study performed to GLP and OECD current guidelines

Additional information

Justification for selection of acute toxicity – oral endpoint

Only study available for this endpoint with this substance. Study performed to GLP and internationally accepted guidelines

Justification for classification or non-classification

In accordance to REGULATION (EC) No 1272/2008, classification is not necessary for acute oral toxicity based on the available data.