Androstan-17-one, 2,3-epoxy-16-(1-pyrrolidinyl)-, (2.alpha.,3.alpha.,5.alpha.,16.beta.)-

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

19 November 1997 to 1 January 1998

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Deviations:

not specified

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

not specified

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Test material

Test material information

Constituent 1

Reference substance name:

928-664-5

EC Number:

928-664-5

IUPAC Name:

928-664-5

Constituent 2

Reference substance name:

(1S,2S,4R,6S,8S,11R,12S,14S,16S)-2,16-dimethyl-14-(pyrrolidin-1-yl)-5-oxapentacyclo[9.7.0.0²,⁸.0⁴,⁶.0¹²,¹⁶]octadecan-15-one

Cas Number:

159325-45-8

Molecular formula:

C23H35NO2

IUPAC Name:

(1S,2S,4R,6S,8S,11R,12S,14S,16S)-2,16-dimethyl-14-(pyrrolidin-1-yl)-5-oxapentacyclo[9.7.0.0²,⁸.0⁴,⁶.0¹²,¹⁶]octadecan-15-one

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): Epyrron
- Physical state: Off white powder
- Analytical purity: 55%
- Composition of test material, percentage of components: Other 22%; 18%
- Lot/batch No.: GV-1458 K1
- Expiration date of the lot/batch: 24 September 1998
- Stability under test conditions: Stable under storage
- Storage condition of test material: At room temperature in the dark

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Charles River, Germany
- Age at study initiation: 6 weeks old
- Weight at study initiation: Less than 500 grams
- Housing: Metal cages with wire-mesh floors
- Diet: Free access to standard guinea pig diet, including ascorbic acid (1600 mg/kg); LC 23-B, pellet diameter 4 mm (Hope farms, Woerden, The Netherlands).
- Water: Free access to tap water, diluted with decalcified water.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 °C
- Humidity (%): 50%
- Air changes (per hr): 15/hours
- Photoperiod (hrs dark / hrs light): 12/12 - artificial fluorescent light

IN-LIFE DATES: From: 09 November 1997 To: 1 January 1998

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

corn oil

Induction 2

Concentration / amount:

Induction: 1%, 2%, and 50%;

Challenge: 50%

Challenge

Challenge 1

Route:

epicutaneous, semiocclusive

Vehicle:

corn oil

Challenge 2

Concentration / amount:

Induction: 1%, 2%, and 50%;

Challenge: 50%

No. of animals per dose:

10

Details on study design:

RANGE FINDING TESTS:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: Three
- Exposure period: 10 days
- Test groups: 10 animals
- Control group: 5 animals
- Site: Scapular region
- Frequency of applications: Day 1, Day 7 and Day 8
- Duration: 48 hours - Day 8
- Concentrations: 1%, 2%, and 50%

B. CHALLENGE EXPOSURE
- No. of exposures: One
- Day(s) of challenge: Day 22 and Day 23
- Exposure period: 24 hours
- Test groups: 10 animals
- Control group: 5 animals
- Site: Scapular region
- Concentrations: 50%
- Evaluation (hr after challenge): 24 and 48 hours

OTHER:

Challenge controls:

Vehicle - corn oil

Positive control substance(s):

not specified

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

50%

No. with + reactions:

10

Total no. in group:

10

Clinical observations:

Moderate to intense erythema and swelling

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50%. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: Moderate to intense erythema and swelling.

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

50%

No. with + reactions:

10

Total no. in group:

10

Clinical observations:

Moderate to intense erythema and swelling

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50%. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: Moderate to intense erythema and swelling.

Any other information on results incl. tables

Challenge
Animal No.	Day 24		Day 25		Comments
	50%#	Vehicle	50%	Vehicle
Control
66	0	0	0	0
67	0	0	0	0
68	0	0	0	0
69	0	0	0	0
70	0	0	0	0
Experimental
71	3	0	4n	2	Sensitised
72	3	0	4n	0	Sensitised
73	4n	0	4s	1	Sensitised
74	3	0	3n	2	Sensitised
75	3	0	4n	0	Sensitised
76	3	0	3n	0	Sensitised
77	4n	0	4s	0	Sensitised
78	2	0	3s	0	Sensitised
79	2	0	3n	0	Sensitised
80	2	0	2	0	Sensitised

#. Test substance concentration

n. Signs of necrosis

s. Eschar formation.

Applicant's summary and conclusion

Interpretation of results:

sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study it can be concluded that the test substance would be considered a sensitisation agent.