9β,11β-epoxy-6α-fluoro-17,21-dihydroxypregna-1,4-diene-3,20-dione 21-acetate

Eye irritation

Administrative data

Endpoint:

eye irritation

Remarks:

in vitro

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment.

Data source

Reference

Reference 1

Reference Type:

other: Protocol Draft

Title:

Draft Updated ICCVAM Recommended HET-CAM Protocol

Author:

ICCVAM

Year:

2010

Bibliographic source:

ICCVAM Test Method Evaluation Report: Current Validation Status of In Vitro Test Methods Proposed for Identifying Eye Injury Hazard Potential of Chemicals and Products - NIH Publication No. 10-7513

Report date:

2010

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

ANNEX - A Sequential Testing Strategy for Eye Irritation and Corrosion .

Test guideline 2

Qualifier:

according to guideline

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.

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Prednisolone

EC Number:

200-021-7

EC Name:

Prednisolone

Cas Number:

50-24-8

IUPAC Name:

11,17,21-trihydroxypregna-1,4-diene-3,20-dione

Details on test material:

- Name of test material (as cited in study report): Prednisolone
- Physical state: chrystalline white powder
- Analytical purity: 99.8 %
- Lot/batch No.: 1153320/MP36894
- Expiration date of the lot/batch: 21/10/2012
- Storage condition of test material: at room temperature, protected fron light

Test system

Vehicle:

physiological saline

Remarks:

B. Braun Melsungen, lot n. 017A122, expiry date: 03/2013.

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

Results and discussion

In vivo

Results

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: Not relevant

Score:

0

Max. score:

21

Remarks on result:

other: Prednisolone was classified as non-irritant.

Any other information on results incl. tables

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.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: other: Read-across approach

Conclusions:

On the basis of the read-across results, interpreted according to ICCVAM Recommended HET-CAM Protocol, because the test product "PREDNISOLONE" is considered NOT IRRITANT for the eye, also the structurally related compound 9β,11β-epoxy-6α-fluoro-17,21-dihydroxypregna-1,4-diene-3,20-dione 21-acetate should be considered as NOT IRRITANT.