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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
2014
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other: GLP-compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment.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 Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
mouse local lymphnode assay (LLNA)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Prednisolone
- Physical state: chrystalline 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 from light.

In vivo test system

Test animals

Species:
mouse
Strain:
CBA
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann, 33178 Bochen, Germany
- Strain: CBA/CaOlaHsd mice
- Age at study initiation: 8-9 weeks
- Weight at study initiation: 18-22 g
- Housing: Full barrier in an air-conditioning room. The animals were kept in groups of 5 animals in IVC cages, type II L, polysulphone cages on Altromin saw fibre bedding.
- Diet (e.g. ad libitum): Free access to Altromin 1324 maintenance diet for rats and mice (lot no. 1315)
- Water (e.g. ad libitum): Free access to tap water, sulphur acidified to a pH of approx. 2.8
- Acclimation period: At least five days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr): at least 10 x
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark

Study design: in vivo (LLNA)

Vehicle:
acetone/olive oil (4:1 v/v)
Remarks:
The preparations were made immediately prior to each use.
Concentration:
The maximum technically applicable concentration of prednisolone was found to be 25 % in AOO (Acetone/Olive Oil 4:1). Thus, a preliminary test was assessed for sensitising properties at concentrations of 6.25 %, 12.5%, and 25% (w/v).
No. of animals per dose:
5 mice per test group (6.25 %, 12.5 %, 25 %, and negative control group).
Moreover 5 animals were used for the positive control assay with p-phenilenediamine.
Positive control substance(s):
other: p-Phenylenediamine (CAS 106-50-3, Sigma, purity > 98%; lot n. 069K0076) 1%, applied on three consecutive days.

Results and discussion

Positive control results:
Application of p-Phenilenediamine gave a stimulation index ranging from 6.1 to 11.2 with a median value of 8.6. A substance is regarded as sensitiser in the LLNA with a Stimulation Index equal to or greater than 3.0.

In vivo (LLNA)

Resultsopen allclose all
Parameter:
SI
Remarks on result:
other: The stimulation index at a concentration of 6.25 % was 0.03 The stimulation index at a concentration of 12.5 % was 0.08 The stimulation index at a concentration of 25 % was 0.03
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: see Remark
Remarks:
The DPM median value at a concentration of 6.25 % was 48.0 (± 22.4) The DPM median value at a concentration of 12.5 % was 114.8 (± 38.9) The DPM median value at a concentration of 25 % was 57.6 (± 37.1) The DPM median value of the Negative Control was 1335.4 (± 217.3) The DPM median value of the Positive Control was 10255.0 (± 2101.7)

Any other information on results incl. tables

 Test Item  CPM  Conc. %  Animal number  DPM  Stimulation Index
 Prednisolone  17.0  6.25  1  35.0  0.02
 Prednisolone  43.0  6.25  2  86.0  0.05
 Prednisolone  14.0  6.25  3  29.0  0.01
 Prednisolone  21.0  6.25  4  42.0  0.02
 Prednisolone  137.0*  6.25  5  334.0*  n.d.
 Prednisolone  67.0  12.5  6  134.0  0.09
 Prednisolone  45.0  12.5  7  89.0  0.06
 Prednisolone  60.0  12.5  8  119.0  0.08
 Prednisolone  86.0  12.5  9  173.0  0.12
 Prednisolone  30.0  12.5  10  59.0  0.03
 Prednisolone  51.0  25  11  103.0  0.07
 Prednisolone  50.0  25  12  100.0  0.07
 Prednisolone  10.0  25  13  20.0  0.00
 Prednisolone  23.0  25  14  46.0  0.02
 Prednisolone  10.0  25  15  19.0  0.00
 Negative Control  670.0   16  1345.0  
 Negative Control  852.0    17  1719.0  
 Negative Control  626.0    18  1263.0  
 Negative Control  519.0    19  1048.0  
 Negative Control  647.0    20  1302.0  
 p-Phenylenediamine 3512.0   1  21  7308.0  6.1
 p-Phenylenediamine  4258.0  1  22  8937.0  7.5
 p-Phenylenediamine  4811.0  1  23  9939.0  8.4
 p-Phenylenediamine   6376.0  1  24  13277.0  11.2
 p-Phenylenediamine   5650.0  1  25  11814.0  9.9

CPM: counts per minute; Conc.: Concentration; DPM: disintegration per minute.

* = outlier, failed Grubbs, Nalimov, and Dixon; n.d.: not determined.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: other: Read-across approach
Conclusions:
Because of, according to OECD 429 and the criteria given in Annex I of Regulation (EC) 1272/2008, the test item Prednisolone, as described in this report is expected to have no sensitising properties and therefore should not be regarded as a dermal sensitiser, the substance 6ß-chloro-17α-hydroxypregna-4-ene-3,20-dione, 17-acetate should be considered as NOT SENSITISER.