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

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 5 May 1994 to 30th August 1994

Reliability:

1 (reliable without restriction)

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 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

24th February 1987

GLP compliance:

yes

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 / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Elevage Cunicole de Val de Selle, 80160 Pouzel, France
- Age at study initiation: not specified
- Weight at study initiation: 2.5 +/- 0.1 kg
- Housing: the animals were housed individually in polystyrene cages (35 x 55 x 32 cm) or (48.2 x 58 x 36.5 cm). Each cage was equipped with a food container and a water bottle.
- Diet (e.g. ad libitum): free access to 112 pelleted diet. Each batch of food was analysed by the supplier
- 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

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18+/- 3°C
- Humidity (%): 30 to 70 %
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12h/12h

IN-LIFE DATES: From: 1 June 1994 To: 5 June 1994

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution):

VEHICLE
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution):
- Lot/batch no. (if required):
- Purity:

Duration of treatment / exposure:

A single introduction of 100 mg of the test substance in its original form was placed into the conjunctival sac of the left eye of 3 animals after gently pulling the lower lid away from the eyeball. The lower and upper eyelids were held together for about one second to avoid any loss of test substance. The right eye, which remained untreated, served as a control.
The eyes were not rinsed after administration of the test substance.

Observation period (in vivo):

Date of treatment: 1.6.94 (day 1)
End of the observation period: 4.6.94 or 5.6.94.
The eye were examined approximately 1, 24, 48, 72 hours after administration of the test substance.
When there is persistent ocular irritation after 72h, the observation period is extended to a maximum of 21 days (unti day 22) in order to determine the progress of the lesions and their reversibility of irreversibility. Any change in the behaviour was noted.

Number of animals or in vitro replicates:

3 animals

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no


SCORING SYSTEM:

TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.3

Max. score:

3

Reversibility:

fully reversible within: 4 days

Results 2

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Results 3

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 3 days

Results 4

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 4 days

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 3 days

Results 6

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 4 days

Results 7

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Results 8

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Results 9

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 3 days

Results 10

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.7

Max. score:

1

Reversibility:

fully reversible within: 4 days

Results 11

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 3 days

Results 12

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 5 days

Any other information on results incl. tables

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

Rabbit number	Ocular region	Description of ocular reactions	Scores					Mean irritation scores (24, 48, 72h)	Interpretation
			1h (D1)	24h (D2)	48h (D3)	72h (D4)	96h (D5)
01	Conjunctivae	Chemosis	3	3	1	0		1.3	Non-irritant
		Redness	1	2	1	0		1.0	Non-irritant
		Discharge	0	2	0	0		0.7
	Iris		0	0	0	0		0.0	Non-irritant
	Corneal opacity	Intensity	0	1	1	0		0.7	Non-irritant
		Area	0	2	1	0		1.0
	Other		none	none	none	none
02	Conjunctivae	Chemosis	2	0	0	0		0.0	Non-irritant
		Redness	2	1	0	0		0.3	Non-irritant
		Discharge	2	0	0	0		0.0
	Iris		0	0	0	0		0.0	Non-irritant
	Corneal opacity	Intensity	0	1	0	0		0.3	Non-irritant
		Area	0	1	0	0		0.3
	Other		none	none	none	none
03	Conjunctivae	Chemosis	3	1	0	0	0	0.3	Non-irritant
		Redness	1	2	1	0	0	1.0	Non-irritant
		Discharge	2	2	0	0	0	0.7
	Iris		0	1	0	0	0	0.3	Non-irritant
	Corneal opacity	Intensity	0	1	1	1	0	1.0	Non-irritant
		Area	0	4	2	2	0	2.7
	Other		none	none	none	none	none

D = day

 

 

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

As the mean scores for chemosis, redness, iris, degree of corneal opacity for 2 out of the 3 animals did not reach the criteria values for irritation, under the experimental conditions of the test, Hydroxybenzomorpholine was considered as non-irritant when administered by ocular route in rabbits.

Executive summary:

A 100 mg sample of neat hydroxybenzomorpholine was instilled into the conjunctival sac of the left eye of 3 male rabbits after gently pulling the lower lid away from the eye ball. The lids were then held together for about one second to avoid any loss of test substance, and the eyes were not rinsed after instillation. The untreated right eye served as control, and ocular reactions were assessed 1, 24, 48, 72 and 96 hours after instillation.

Results
Marked conjunctival reactions (marked chemosis, slight to moderate redness) were observed in all animals one hour after instillation. These conjunctival reactions fully disappeared within 72 hours of instillation. Moderate to marked corneal opacity was observed in all animals on the day after instillation and fully disappeared within 96 hours. Isolated ocular discharge and minimal iris lesions were also observed.

Conclusion
Under the conditions of this study, hydroxybenzomorpholine was considered to be moderately irritating to rabbit eyes when tested undiluted.