3,4-dihydro-2H-1,4-benzoxazin-6-ol

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 05 May 1994 to 25 August 1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

17 July 1992

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

3,4-dihydro-2H-1,4-benzoxazin-6-ol

EC Number:

247-415-5

EC Name:

3,4-dihydro-2H-1,4-benzoxazin-6-ol

Cas Number:

26021-57-8

Molecular formula:

C8H9NO2

IUPAC Name:

3,4-dihydro-2H-1,4-benzoxazin-6-ol

Test material form:

solid: particulate/powder

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage Cunicole de Val de Selle, 80160 Prouzel, France
- Age at study initiation: not specified
- Weight at study initiation: mean body weight of 2.4 ± 0.1 kg
- Housing: the animals were housed individually in polystyrene cages (35 x 55 x 32 em or 48.2 x 58 x 36.5 em). Each cage was equipped with a food container and a water bottle.
- Diet (e.g. ad libitum): All the animals had free access to 112 C pelleted diet (U.A.R., 91360 Villemoisson-sur-Orge, France).
- Water (e.g. ad libitum): drinking water filtered by a F.G. Millipore membrane (0.22 micron) and contained in bottles was provided ad libitum.
- Acclimation period: at least 5 days before the beginning of the study

There were no contaminants in the diet or water at levels likely to have influenced the outcome of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3°C
- Humidity (%): 50 ± 20%
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: From 25 May 1994 To 28 May 1994

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
A dose of 500 mg of the test substance in its original form was applied to a 6 cm² hydrophilic gauze patch moistened with 0.5 ml of water for injections and this was then applied to the right flank.

NEGATIVE CONTROL
The left flank did not receive any test substance and served as control.

Duration of treatment / exposure:

The test substance was applied to the right flank of rabbits for 4 hours.

Observation period:

The skin was examined approximately 1, 24, 48 and 72 hours after removal of the dressing. When there is no evidence of dermal irritation after 72 hours, the study is ended. Any change in the animals' behaviour was noted.

Number of animals:

3

Details on study design:

TEST SITE
The day before treatment, the flanks of each animal were clipped using electric clippers. Only animals showing no obvious signs of irritancy were used for the study.
The test substance and the gauze patch were held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage.

REMOVAL OF TEST SUBSTANCE
Four hours after application, the dressings were removed and any residual test substance was removed with a dry gauze patch.

OBSERVATION TIME POINTS
1, 24, 48 and 72 hours after removal of the dressing

SCORING SYSTEM:
Dermal irritation was evaluated for each animal according to the following scoring scale:

Erythema and eschar formation:
no erythema .......................................................................................................... 0
very slight erythema (barely perceptible) ............................................................. 1
well-defined erythema .......................................................................................... 2
moderate to severe erythema ............................................................................. 3
severe erythema (beet redness) to slight eschar formation (injuries in depth) 4

Oedema formation
no oedema............................................................................................................. 0
very slight oedema (barely perceptible) .............................................................. 1
slight oedema (edges of area well-defined by definite raising) ......................... 2
moderate oedema (raised approximately 1 millimetre)...................................... 3
severe oedema (raised more than 1 millimetre and extending beyond area
of exposure) .......................................................................................................... 4

Any other lesions were noted.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No cutaneous reactions were observed during the study.

Other effects:

None.

Any other information on results incl. tables

Table 1: Individual cutaneous examinations and mean score of the values recorded after 24, 48 and 72 hours for each animal

Rabbit number	Dermal irritation	Scores				Mean irritation scores (24, 48, 72h)	Interpretation
		1h	24h	48h	72h
01	Erythema	0	0	0	0	0.0	Non-irritant
	Oedema	0	0	0	0	0.0	Non-irritant
	Other	none	none	none	none
02	Erythema	0	0	0	0	0.0	Non-irritant
	Oedema	0	0	0	0	0.0	Non-irritant
	Other	none	none	none	none
03	Erythema	0	0	0	0	0.0	Non-irritant
	Oedema	0	0	0	0	0.0	Non-irritant
	Other	none	none	none	none

 

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the experimental conditions of this test, the test substance hydroxybenzomorpholine was considered as non-irritant when administered by cutaneous route in rabbits.

Executive summary:

Approximately 24 hours prior to the application of hydroxybenzomorpholine, the flanks of 3 male rabbits were clipped free of fur. A 500 mg sample of neat hydroxybenzomorpholine moistened with 0.5 ml water was applied to a 6 cm² area of the right flank of each animal (the untreated left flank served as control). It was held in contact with the skin for 4 hours by means of a semiocclusive dressing.

Subsequently, the dressings were removed, any residual test substance was removed and the treated area was observed 1, 24, 48 and 72 hours afterwards.

Results
There were no skin reactions at any observation time-point.

Conclusion
Under the conditions of this study, hydroxybenzomorpholine was non-irritating to rabbit skin when tested undiluted.