16α,17,21-trihydroxypregna-1,4,9(11)-triene-3,20-dione 21-acetate

Skin sensitisation

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other: GLP-compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment.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

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

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 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)

Results

Results 1

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

Results 2

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 16a,17,21-trihydroxypregna-1,4,9(11)-triene-3,20-dione 21-acetate should be considered as NOT SENSITISER.