5H-dibenz[b,f]azepine

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

other information

Study period:

April 28 to May 09, 1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented and reported study, conducted according to internationally accepted technical guideline and in compliance with GLP in recognized industrial research organization.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

of 1992

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

5H-dibenz[b,f]azepine

EC Number:

205-970-0

EC Name:

5H-dibenz[b,f]azepine

Cas Number:

256-96-2

Molecular formula:

C14H11N

IUPAC Name:

5H-dibenzo[b,f]azepine

Details on test material:

- Name of test material (as cited in study report): PBS 7049
- Supplier: Pharma Chemical Production
- Description: orange crystalline powder
- Expiration date of the lot/batch: 03/96
- Storage conditions: room temperature

Test animals

Species:

rabbit

Strain:

other: Russian rabbit, Chbb:HM (SPF)

Details on test animals or test system and environmental conditions:

- Animal supplier: Dr. K. Thomae, GmbH, Biberach (FRG)
- Initial Age (at dosing): 41 - 43 weeks.
- Number and sex of animals: 3 female rabbits.
- Weight on day of treatment (at dosing): Minimum 2.793 kg, maximum 2.925 kg.
- Housing: Individual housing in stainless steel cages.
- Diet (ad libitum): Commercially available pelleted standard diet (NAFAG No. 814, analysed by the
manufacturer, NAFAG, 9202 Gossau, Switzerland).
- Water (ad libitum): Tap water. (Periodically analysed)
- Acclimation period: At least 5 days under laboratory conditions.


ENVIRONMENTAL CONDITIONS

Air conditioned room:
- Temperature (°C): 20 ± 3°C
- Relative Humidity (%): 30 to 70%
- Photoperiod: 12 hrs artificial light/day

Test system

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.5 g test material per approx. 6 cm2 skin per animal. The unchanged test material was loaded on gauze patches moistened with physiological saline (0.9% formulation from B. Braun Medical AG, St. Gallen, Switzerland).

Duration of treatment / exposure:

single exposure for 4 hours

Observation period:

From prior to treatment (i.e. predose) until 7 days post patch removal

Number of animals:

3 (females)

Details on study design:

TEST SITE PREPARATION:

Approximately 3 days before treatment, both flanks of the rabbits were shaved with an electric clipper.

- Area of treated skin: Approx. 6 cm2 (= 2.5 x 2.5 cm gauze patch).
- Type of wrap used: Gauze patches were loosely covered with plastic foil and fastened to the rabbit body with adhesive tape.

TEST MATERIAL AND DOSE PREPARATION

- Administration Volume/animal (on a gauze patch of approx. 6 cm2 per animal):
0.5 g unchanged test material was loaded on a gauze patch moistened with physiological saline.
On the contralateral flank the wetting agent alone, physiological saline, was administered using another gauze patch.

TREATMENT PERIOD AND REMOVAL OF TEST SUBSTANCE

Topical, occlusive treatment lasted 4 hours. Then the dressings were removed.

SCORING SYSTEM:

The treated skin patches were evaluated at predose and 60 minutes 24, 48 and 72 hours and 7 days post patch removal. Skin reactions were evaluated for erythema/eschar formation and edema according to the cited test guideline (OECD 404 of 1992).

GENERAL OBSERVATIONS
The animals were checked for mortality and clinical signs. In addition, bodyweights were recorded at predose and on Days 2, 3, 6 and 7.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

overall irritation score

Basis:

mean

Remarks:

over 3 animals and 3 time points

Time point:

other: 24, 48, 72 h

Score:

1.11

Max. score:

8

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Two of three animals showed erythema and edema reactions on the treated skin patch. Skin reactions were not evident in patches exposed to the wetting agent alone.

Results 2

Irritation parameter:

erythema score

Basis:

mean

Remarks:

over 3 animals and 3 time points

Time point:

other: 24, 48, 72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 7days

Remarks on result:

other: Two of three animals showed erythema reactions on the treated skin patch. Skin reactions were not evident in patches exposed to the wetting agent alone.

Results 3

Irritation parameter:

edema score

Basis:

mean

Remarks:

over 3 animals and 3 time points

Time point:

other: 24, 48, 72 h

Score:

0.44

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Two of three animals showed edema reactions on the treated skin patch. Skin reactions were not evident in patches exposed to the wetting agent alone.

Irritant / corrosive response data:

Erythema and edema result tables for each individual animal are presented under "Remarks on results including tables and figures"

Other effects:

There were no mortality, clinical signs and no adverse effects on bodyweight.

Any other information on results incl. tables

   

Table 1: Gradings of Skin Reactions to PBS 7049 Attained for each Female Animal at Different Observation Time Points
Pretest / Time after Patch Removal	Pretest	1 h	24 h	48 h	72 h	7 days
Animal (Identification) No.	1   2   3	1   2   3	1   2   3	1   2   3	1   2   3	1   2   3
Erythema / Eschar	0   0   0	0   0   0	0   1   0	0   1   0	0   2   2	0   0   0
Edema	0   0   0	0   0   0	0   1   0	0   1   0	0   1   1	0   0   0

 

 

Skin reactions were not evident in patches exposed to the wetting agent alone.

 

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Although the minor skin reactions attained in the present study may reflect a slightly skin irritating effect, according to EU classification rules (DIRECTIVE 67/548/EEC and REGULATION (EC) 1272/2008) the test material is "not irritant" not necessitating any labelling regarding skin irritation.

Executive summary:

PBS 7049 was tested for skin irritation according to OECD Guideline 404 and in compliance with GLP. Reliability grade 1 was assigned to the study.

 

Each of three Russian rabbits [Chbb:HM (SPF)] was treated for 4 hours by topical, occlusive administration of a single dose of 0.5 g test substance to shaved intact skin (approximately 6 cm2/animal). A gauze patch moistened with physiological saline was used for administration. On the contralateral flank physiological saline was administered in the same way to shaved intact skin and served as a control using another gauze patch. The site of administration was examined for skin reactions at 1, 24, 48 and 72 hours and at 7 days post patch removal. In addition, general clinical signs, mortality and bodyweights were recorded.

 

There was no mortality. General symptoms or relevant changes in body weight were not evident. Erythema up to grade 2 (well defined) and very slight edema (Grade 1, barely perceptible) were seen in 2 of 3 animals and were attributed to treatment with the test material. By 7 days after patch removal all skin reactions had fully reversed to normal skin in the affected animals. In the remaining one animal skin reactions to PBS 7049, were not evident. Physiological saline alone did also not elicit any skin reactions.

 

The mean Draize scores (24, 48, 72 h over 3 animals) were 0.67 for erythema and 0.44 for edema. For each of the two affected animals, the mean scores (24, 48, 72 h) for erythema and those for edema were < 2. Although the skin reactions attained may reflect a slightly skin irritating effect, according to EU classification rules (DIRECTIVE 67/548/EEC and REGULATION (EC) 1272/2008) the test material is "not irritant" not necessitating any labelling regarding skin irritation.