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Administrative data

Description of key information

Based on the results of two reliable in vitro studies conducted with a structural analogue prednisolone, Prediac-Z is considered not irritating and not corrosive to skin.

Based on the results of a reliable chorioallantoic membrane assay conducted with a structural analogue prednisolone, Prediac-Z is considered not irritating to eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin corrosion: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 435 (In Vitro Membrane Barrier Test Method for Skin Corrosion)
Version / remarks:
2006
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test system:
artificial membrane barrier model
Vehicle:
unchanged (no vehicle)
Amount/concentration applied:
500 mg
Irritation / corrosion parameter:
penetration time (in minutes)
Run / experiment:
1
Value:
> 60
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Irritation / corrosion parameter:
penetration time (in minutes)
Run / experiment:
2
Value:
> 60
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Irritation / corrosion parameter:
penetration time (in minutes)
Run / experiment:
3
Value:
> 60
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Irritation / corrosion parameter:
penetration time (in minutes)
Run / experiment:
4
Value:
> 60
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid

 Replicate    Started at ti (hh:mm:ss)  Ended at tf (hh:mm:ss)  Corrosion time (hh:mm:ss)  Mean corrosion time (hh:mm:ss)  RESULT
 Prednisolone  1  11:23:26  End test*  > 60 minutes > 60 minutes     Not Corrosive
 2  11:25:01  End test*  > 60 minutes
 3  11:26:13  End test*  > 60 minutes
 4  11:27:36  End test*  > 60 minutes
 Negative Control  1  11:29:33  12:36:24  1:06:51  > 60 minutes  Not Corrosive
 Positive Control  1  11:33:27  11:34:42  0:01:51  0:01:51  Corrosive

* The End time of testing is equivalent to that of negative control.

Interpretation of results:
GHS criteria not met
Conclusions:
The test substance "PREDNISOLONE", assigned to Category 2 (weak acids and bases), did not cause corrosion of the biobarrier in time to the classification according to UN Packing Trasportation Group. On the basis of the results, interpreted according to OECD N° 435 of July 19, 2006, the test substance "PREDNISOLONE" is classified as NOT CORROSIVE.
Endpoint:
skin irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
Version / remarks:
2010
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test system:
human skin model
Source species:
human
Cell type:
non-transformed keratinocytes
Details on test system:
RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: Skinethic RHE is a 3D system of reconstructed epidermis of normal human keratinocytes.
Cells are grown on inert polycarbonate filter on chemically defined medium, airlifted for 17 days. The model exhibits normal barrier functions (presence of a differentiated stratum corneum).

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: room temperature

NUMBER OF REPLICATE TISSUES: triplicate

PREDICTION MODEL / DECISION CRITERIA:
The test substance is considered to be irritant to skin, if the mean relative viability after 42 minutes exposure and 42 hours post incubation is less or equal to 50 % of the negative control.

ACCEPTABILITY CRITERIA
The negative control data meet the acceptance criteria if the mean OD value of the 3 tissues at 570 nm is: 1.2 ≤ OD ≤ 2.5 The positive control data meet the acceptance criteria if the mean viability, expressed as % of the NC, is ≤ 40 %. In both cases, the standard deviation value will be considered valid if it is ≤ 18 % according to the performance standard (ECVAM SIVS, 2007).
Control samples:
yes, concurrent negative control
yes, concurrent positive control
Duration of treatment / exposure:
42 minutes
Number of replicates:
Triplicate
Irritation / corrosion parameter:
other:
Run / experiment:
1-9 (mean of 9 experiments)
Value:
60.96
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid

Optic density (OD) at 570 nm

 REPLICA  1  2  3  4  5  6  7  8  9
 Blank 0.090   0.089  0.092  0.093  0.090  0.090  -  -  -
 Negative control  1.273  1.407  1.422  1.451  1.445  1.440  1.412  1.416  1.418
 Positive control  0.130  0.143  0.142  0.140  0.141  0.143  0.139  0.141  0.146
 Prednisolone  0.780  0.910  0.905  0.946  0.915  0.914  0.907  0.901  0.884

   Average OD  Acceptability  Result  SD %  Acceptability (%)  Result
 Negative control  1.32  1.2 ≤ OD ≤ 2.5  Complying  3.762  ≤ 18  Complying
 Positive control  3.74  < 40 %  Complying  2.837  ≤ 18  Complying

 SAMPLE  % VIABILITY  ACCEPTABILITY
 PREDNISOLONE  60.96  > 50 %
Interpretation of results:
not irritating
Remarks:
Criteria used for interpretation of results: OECD GHS
Conclusions:
On the basis of the results, interpreted according to OECD 439 and SKINETHIC SOP (January 2009), the test product "PREDNISOLONE" must be considered NOT IRRITANT for the skin.
Endpoint:
skin corrosion: in vitro / ex vivo
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 435 (In Vitro Membrane Barrier Test Method for Skin Corrosion)
Version / remarks:
2006
Deviations:
no
Irritation / corrosion parameter:
penetration time (in minutes)
Run / experiment:
1
Value:
> 60
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Irritation / corrosion parameter:
penetration time (in minutes)
Run / experiment:
2
Value:
> 60
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Irritation / corrosion parameter:
penetration time (in minutes)
Run / experiment:
3
Value:
> 60
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Irritation / corrosion parameter:
penetration time (in minutes)
Run / experiment:
4
Value:
> 60
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid

 Replicate    Started at ti (hh:mm:ss)  Ended at tf (hh:mm:ss)  Corrosion time (hh:mm:ss)  Mean corrosion time (hh:mm:ss)  RESULT
 Prednisolone  1  11:23:26  End test*  > 60 minutes > 60 minutes     Not Corrosive
 2  11:25:01  End test*  > 60 minutes
 3  11:26:13  End test*  > 60 minutes
 4  11:27:36  End test*  > 60 minutes
 Negative Control  1  11:29:33  12:36:24  1:06:51  > 60 minutes  Not Corrosive
 Positive Control  1  11:33:27  11:34:42  0:01:51  0:01:51  Corrosive

* The End time of testing is equivalent to that of negative control.

Interpretation of results:
GHS criteria not met
Conclusions:
In a reliable study with a structural analogue of Prediac-Z, prednisolone, the test substance prednisolone did not cause corrosion of the biobarrier within 60 minutes. On the basis of the results, interpreted according to OECD N° 435 of July 19, 2006, the test substance prednisolone is considered not corrosive. This result can be read across to Prediac-Z.
Endpoint:
skin irritation: in vitro / ex vivo
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 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
Version / remarks:
2010
Deviations:
no
Irritation / corrosion parameter:
other:
Run / experiment:
1-9 (mean of 9 experiments)
Value:
60.96
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid

Optic density (OD) at 570 nm

 REPLICA  1  2  3  4  5  6  7  8  9
 Blank 0.090   0.089  0.092  0.093  0.090  0.090  -  -  -
 Negative control  1.273  1.407  1.422  1.451  1.445  1.440  1.412  1.416  1.418
 Positive control  0.130  0.143  0.142  0.140  0.141  0.143  0.139  0.141  0.146
 Prednisolone  0.780  0.910  0.905  0.946  0.915  0.914  0.907  0.901  0.884

   Average OD  Acceptability  Result  SD %  Acceptability (%)  Result
 Negative control  1.32  1.2 ≤ OD ≤ 2.5  Complying  3.762  ≤ 18  Complying
 Positive control  3.74  < 40 %  Complying  2.837  ≤ 18  Complying

 SAMPLE  % VIABILITY  ACCEPTABILITY
 PREDNISOLONE  60.96  > 50 %
Interpretation of results:
GHS criteria not met
Conclusions:
On the basis of the results of a reliable guideline study conducted with a structural analogue of Prediac-Z, prednisolone, the test substance must be considered not irritating to skin. This result can be read across to Prediac-Z.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
ANNEX - A Sequential Testing Strategy for Eye Irritation and Corrosion .
Qualifier:
according to
Guideline:
other: Draft Updated ICCVAM Recommended HET-CAM Protocol.
Principles of method if other than guideline:
Results from in vitro or ex vivo tests: Substances that have demonstrated corrosive or severe irritant properties in an in vitro or ex vivo test that has been validated and accepted for the assessment specifically of eye or skin corrosivity/irritation, need not be tested in animals. It can be presumed that such substances will produce similar severe effects in vivo.
Even if HET-CAM assay have not achieved the OECD validation, it is accepted for the purpose of "TESTING AND EVALUATION STRATEGY FOR EYE IRRITATION/CORROSION" as reported in ANNEX of test method B.5.
GLP compliance:
yes (incl. certificate)
Vehicle:
physiological saline
Remarks:
B. Braun Melsungen, lot n. 017A122, expiry date: 03/2013.
Controls:
yes, concurrent positive control
yes, concurrent negative control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Prednisolone 100 % applied to an area of 25 % of the chorioallantoic membrane.

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.3 mL of standard solution (0.9 % NaCl)
- Lot/batch no. 017A122
Duration of treatment / exposure:
The reaction on the CAM were observed over a period of 5 minuted monitoring the appearance of:
Haemorrhage (bleeding);
Vascular lysis (blood vessel disintegration);
Coagulation (protein denaturation intra- and extravascular).
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done):
- Time after start of exposure: Prednisolone was left in contact with the egg membrane for 5 minutes.

SCORING SYSTEM: the time for each reaction to occur was recorded and an irritation score (IS) was calculated:
IS = [(301-sec H)/300] x 5 x S+ [(301-sec L)/300] x 7 x S + [(301-sec C)/300] x 9 x S

sec = second of first occurence of reaction
H = Haemorrhage
L = Vascular Lysis
C = Coagulation
S = 0.1 if H, C, L is grade 1 (weak reaction)
S = 0.5 if H, C, L is grade 2 (moderate reaction)
S = 1 if H, C, L is grade 3 (strong reaction)
The mean score was calculated from irritation scores for each egg for each test group.

TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein
Irritation parameter:
in vitro irritation score
Run / experiment:
mean
Value:
0
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Interpretation of results:
GHS criteria not met
Conclusions:
The eye irritancy potential of the test item was investigated in the chorioallantoic membrane assay.
The test item was tested as provided by the sponsor in order to find any irritancy potential.
The calculated mean irritation score was 0.
The test item was classified as non-irritant.
The positive and negative controls were within the historical control data range demonstrating the validity and sensitivity of the test.
Endpoint:
eye irritation: in vitro / ex vivo
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:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
ANNEX - A Sequential Testing Strategy for Eye Irritation and Corrosion .
Qualifier:
according to
Guideline:
other: Draft Updated ICCVAM Recommended HET-CAM Protocol.
Principles of method if other than guideline:
Results from in vitro or ex vivo tests: Substances that have demonstrated corrosive or severe irritant properties in an in vitro or ex vivo test that has been validated and accepted for the assessment specifically of eye or skin corrosivity/irritation, need not be tested in animals. It can be presumed that such substances will produce similar severe effects in vivo.
Even if HET-CAM assay heve not achieved the OECD validation, it is accepted for the purpose of "TESTING AND EVALUATION STRATEGY FOR EYE IRRITATION/CORROSION" as reported in ANNEX of test method B.5.
Irritation parameter:
in vitro irritation score
Run / experiment:
mean
Value:
0
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Interpretation of results:
GHS criteria not met
Conclusions:
In a reliable in vitro study conducted with a structural analogue of Prediac-Z, prednisolone, the test substance caused an average in vitro irritancy score of 0. Based on this, prednisolone is considered not an eye irritant. This result can be read across to Prediac-Z.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In a reliable study performed according to OECD guideline 435 (July 19, 2006) with a structural analogue of Prediac-Z, prednisolone, the test substance prednisolone did not cause corrosion of the biobarrier within 60 minutes. On the basis of the results the test substance prednisolone is considered not corrosive. This result can be read across to Prediac-Z.

On the basis of the results of a reliable guideline study conducted according to OECD guideline 439 with a structural analogue of Prediac-Z, prednisolone, the substance is considered not irritating to skin.

In a reliable in vitro chorioallantoic membrane assay conducted with a structural analogue prednisolone, the test substance was not irritating to eye. The calculated mean in vitro irritancy score was 0. The positive and negative controls were within the historical control data range demonstrating the validity and sensitivity of the test.

Based on this, Prediac-Z is considered not irritating to eyes.

Justification for classification or non-classification

Based on the results of reliable in vitro studies conducted with a structural analogue prednisolone, classification of Prediac-Z for skin and eye irritation is not warranted according to Regulation (EC) 1272/2008.