(4aR*, 8aR*)-1-bromo-4a,5,9,10,11,12-hexahydro-3-methoxy-6H-benzofuro[3a,3,2-ef] [2]benzazepin-6-one hydrochloride (1:1)

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2001-09-11 to 2001-09-20

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

rel-(4aR,8aR)-1-bromo-3-methoxy-4a,5,9,10,11,12-hexahydro-6H-[1]benzofuro[3a,3,2-ef][2]benzazepin-6-one hydrochloride (1:1)

EC Number:

700-867-1

Molecular formula:

C16H16BrNO3.HCl

IUPAC Name:

rel-(4aR,8aR)-1-bromo-3-methoxy-4a,5,9,10,11,12-hexahydro-6H-[1]benzofuro[3a,3,2-ef][2]benzazepin-6-one hydrochloride (1:1)

Test material form:

solid

Details on test material:

- Name of test material (as cited in study reports): T002102
- Physical state: solid
- Appearance: white (SDS)

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: RT002102G4A311
- Expiration date of the lot/batch: 2002-03-25 (retest date)
- Purity test date: no data
- Purity: 99.4%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: in the original container, at room temperature (range 17-23°C), away from direct sunlight.
- Stability under test conditions: stable under storage conditions
- Solubility and stability of the test substance in the solvent/vehicle: not applicable
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: not applicable

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: moistened with bi-distilled water before application

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage Scientifique des Dombes, F-01400 Chatillon sur Chalaronne/France
- Age at start of treatment: 10-11 weeks (male and females)
- Weight at day of treatment: 2257 grams (male), 2113 to 2275 grams (females)
- Housing: Individually in stainless steel cages equipped with feed hoppers, drinking water bowls, with wood and haysticks for gnawing.
- Diet (e.g. ad libitum): pelleted standard Provimi Kliba 3418 rabbit maintenance diet, ad libitum
- Water (e.g. ad libitum): community tap water from Fűllinsdorf, ad libitum
- Acclimation period: 2001-09-11 to 2001-09-16, under laboratory conditions after health examination

ENVIRONMENTAL CONDITIONS
- Temperature (deg C): 17-23 °C
- Humidity (%): 30-70%
- Air changes (per hr): approximately 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark, music was played during the light period

IN-LIFE DATES: From: 2001-09-17 To: 2001-09-20

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g/animal, weighed as delivered and then moistened with bi-distilled water before appliction.
- Concentration (if solution): not applicable

Duration of treatment / exposure:

4 hours

Observation period:

72 hours after treatment

Number of animals:

3 animals (one male and 2 females)

Details on study design:

TEST SITE
- Area of exposure: flank of the animal. On the day of treatment, 0.5 g of the test substance was placed on a surgical gauze patch (2.5 cm x 2.5 cm). This patch was applied to approximately 6 cm2 of the intact skin of the clipped area.
- % coverage: no data
- Type of wrap if used: semi-occlusive dressing. Dressing was wrapped around the abdomen and anchored with tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After treatment, the dressing was removed and the skin was flushed with lukewarm tap water to clean the application site.
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS: 24, 48 and 72 hours after patch removal

SCORING SYSTEM:
- The skin reaction was assessed according to the numerical scoring system listed in the EEC Commission Directive 92/69/EEC, July 31, 1991.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Remarks:

male 96

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

erythema score

Basis:

mean

Remarks:

female 97

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

erythema score

Basis:

mean

Remarks:

female 98

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

edema score

Basis:

mean

Remarks:

male 96

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

edema score

Basis:

mean

Remarks:

female 97

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

edema score

Basis:

mean

Remarks:

female 98

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

The mean for erythema/eschar score of the three animals was 0.33, 0.00, and 0.00, respectively and the mean oedema score was 0.00 for all three animals.
Very slight erythema was observed at the test site of one animal from 1 to 24 hours after treatment.
No abnormal findings were observed at the test site of any animal at either the 48- or 72-hour readings.
No irreversible alterations of the treated skin were observed, nor were corrosive effects evident on the skin.

Other effects:

No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.
No staining by the test substance of the treated skin was observed.
The body weights of all rabbits were considered to be within the normal range of variability.

Any other information on results incl. tables

Animal number	Sex	Evaluation Interval	Erythema	Oedema	Scaling
96	M	1 hour	1	0	0
97	F	1 hour	0	0	0
98	F	1 hour	0	0	0
96	M	24 hour	1	0	0
97	F	24 hour	0	0	0
98	F	24 hour	0	0	0
96	M	48 hour	0	0	0
97	F	48 hour	0	0	0
98	F	48 hour	0	0	0
96	M	72 hour	0	0	0
97	F	72 hour	0	0	0
98	F	72 hour	0	0	0

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test substance was considered to be "not irritating" to rabbit skin under the conditions of this study and therefore not to be classified according to CLP regulation.