4-(oxiran-2-ylmethoxy)-9H-carbazole

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

GLP compliance:

yes (incl. QA statement)

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

The studies were carried out in 2002.

Test material

Test material information

Constituent 1

Reference substance name:

4-[(oxiran-2-yl)methoxy]-9H-carbazole

EC Number:

610-764-2

Cas Number:

51997-51-4

Molecular formula:

C15H13NO2

IUPAC Name:

4-[(oxiran-2-yl)methoxy]-9H-carbazole

Test material form:

solid: crystalline

Details on test material:

- Name of test material (as cited in study report): Carvedilol 4th intermediate (Oxiranylmethoxy carbazole)
- Physical state: chamois powder
- Lot/batch No.: 2002/2
- Expiration date of the lot/batch: 02. 2002
- Storage condition of test material: dry and cool place, protected from light

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: LAB-ÁLL Bt , Hunyadi street 7, Budapest, H-1174, Hungary
- Weight at study initiation: 320-344 g
- Housing: Macrolon cage, size III (42x42x19 cm), 2-3 animals / cage
- Bedding: Laboratory bedding
- Diet (e.g. ad libitum): ad libitum (PURISTAR standard diet for rabbits produced by AGRIBANDS Europe Hungary)
- Water (e.g. ad libitum): ad libitum, tap water for human consumption containing 50 mg / 100 ml Ascorbic acid
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3 °C
- Humidity (%): 30-70 %
- Photoperiod (hrs dark / hrs light): 12 / 12 hours

Study design: in vivo (non-LLNA)

Induction

Route:

intradermal and epicutaneous

Vehicle:

other: 1% Methylcellulose

Concentration / amount:

50 (w/v) % (test item in methyl cellulose (1%) for dermal and challange treatment
0.1 % (in physiological saline and Freund's complete adjuvant for intradermal treatment

Day(s)/duration:

2

Challenge

Route:

epicutaneous, occlusive

Vehicle:

other: 1% Methylcellulose

Concentration / amount:

50 (w/v) % (test item in methyl cellulose (1%) for dermal and challange treatment
0.1 % (in physiological saline and Freund's complete adjuvant for intradermal treatment

Day(s)/duration:

2

No. of animals per dose:

2 animals/two concentrations (in one animal two cincentrations were tested: one concentration in left side, and other concentration in right side) in the range finding study.

10 animals (in test groups)
5 animals (in control groups)

Details on study design:

RANGE FINDING TESTS:
2 dose levels were tested in the preliminari dose range finding study to specify the primary irritationby intradermal injection and dermal application. Two dose levels were tested in the preliminary dose range finding study to specify the primary irritation by intradermal injection and two dose levels by dermal application.

Further information about treatments see under paragraph 'any other information...'

Challenge controls:

5 control guinea pigs were simultaneously exposed to vehicle during the sensitization phase and they were treated with the test item ( at concentration of 10%) only in the case of challenge.

Positive control substance(s):

yes

Remarks:

Potassium dichromate

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:

6

Total no. in group:

10

Clinical observations:

discrete or patchy erythema; moderate and confluent erythema

Remarks on result:

positive indication of skin sensitisation

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

50%

No. with + reactions:

4

Total no. in group:

10

Clinical observations:

discrete or patchy erythema; moderate and confluent erythema

Remarks on result:

positive indication of skin sensitisation

Any other information on results incl. tables

Challenge with the test item elicited patchy and confluent erythema on the skin surface of previously sensitized guinea pigs. The mean of the scores was 0.9 and 0.6. The net scores was 0.5 and 0.4 according to the 24th and 48th hour observations.

In the control group the mean of the scores was 0.4 and 0.2.

Applicant's summary and conclusion

Interpretation of results:

sensitising

Remarks:

Migrated information moderately Criteria used for interpretation of results: EU

Conclusions:

According to the net percentage value of positively responded animals and to the net score value of the skin reactions, the test item CARVEDILOL 4th INTERMEDIATE was classified as moderate sensitizer.