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Description of key information

Based on the results of oral acute toxicity studies with two structural analogues prednisolone and 16alpha-hydroxyprednisolone, Prediac-Z is considered not acutely toxic by oral route (LD50 > 2000 mg/kg bw).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2001
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
This study is reported on RTECS database. The use of secondary sources of data is acceptable when they are based on a critical evaluation of peer-reviewed data and a consequent selection of a reliable and representative value for the property under investigation. Therefore, although the method is unknown, the values presented here are acceptable as they are from a reliable secondary source of biological data.
Principles of method if other than guideline:
No data.
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
not specified
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
not specified
Control animals:
not specified
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
3 857 mg/kg bw
Based on:
test mat.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
3 879 mg/kg bw
Based on:
test mat.
Mortality:
The animals died on the 3rd and 7th day.
Clinical signs:
In a clinical presentation of acute intoxication signs of adrenal insufficiency were observed: lethargy, slovenliness of animals` coat, bloody issues from a nasopharynx.
Body weight:
Weight loss was observed.

TOXIC EFFECT:

- Behavioral: somnolence (general depressed activity).

- Blood: hemorrhage.

- Nutritional and Gross Metabolic: weight loss or decreased weight gain.

Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 reported in male and female rats is higher than 2000 mg/kg bw. Thus, prednisolone was not considered an acute toxicant.
Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: read-across from a structural analogue
Justification for type of information:
The read-across rationale is attached in section 13.
Reason / purpose:
read-across source
Principles of method if other than guideline:
No data.
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
3 857 mg/kg bw
Based on:
test mat.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
3 879 mg/kg bw
Based on:
test mat.
Mortality:
The animals died on the 3rd and 7th day.
Clinical signs:
In a clinical presentation of acute intoxication signs of adrenal insufficiency were observed: lethargy, slovenliness of animals` coat, bloody issues from a nasopharynx.
Body weight:
Weight loss was observed.

TOXIC EFFECT:

- Behavioral: somnolence (general depressed activity).

- Blood: hemorrhage.

- Nutritional and Gross Metabolic: weight loss or decreased weight gain.

Interpretation of results:
GHS criteria not met
Conclusions:
In a study conducted with a structural analogue of Prediac-Z, prednisolone, the LD50 reported in male and female rats was higher than 2000 mg/kg bw. Thus, prednisolone was not considered an acute toxicant. This result can be read across to Prediac-Z.
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Specific details on test material used for the study:
- Storage conditions: room temperature in the dark
Species:
rat
Strain:
other: Hsd (SD) albino rats
Sex:
female
Details on test animals 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.
Key result
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:
GHS criteria not met
Conclusions:
The acute median lethal oral dose (LD50) to rats of 16alpha-hydroxyprednisolone was demonstrated to be greater than 2000 mg/kg bodyweight.
Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: read-across from a structural analogue
Justification for type of information:
The read-across rationale is attached in section 13.
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Control animals:
no
Key result
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:
GHS criteria not met
Conclusions:
In a study conducted with a structural analogue of Prediac-Z, 16alpha-hydroxyprednisolone, the acute median lethal oral dose (LD50) to rats was > 2000 mg/kg bodyweight. This result can be read across to Prediac-Z.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
2 (read-across from a structural analogue)

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In a reliable GLP-compliant OECD guideline 423 study with a structural analogue 16alpha-hydroxyprednisolone, an oral LD50 in rats was > 2000 mg/kg bw. This result is consistent with the results of the study with another structural analogue prednisolone, in which the LD50 > 3000 mg/kg bw was reported. Based on the read-across from two structural analogues, Prediac-Z is considered to be not acutely toxic by oral route (LD50 > 2000 mg/kg bw).

Justification for classification or non-classification

Based on the acute oral LD50 > 2000 mg/kg bw, obtained in the studies with structural analogues prednisolone and 16alpha-hydroxyprednisolone, Prediac-Z does not need to be classify for acute toxicity in accordance with Regulation (EC) 1272/2008.