Ethanone, 2,2-dichloro-1-(2,3-dihydro-3-methyl-4H-1,4-benzoxazin-4-yl)-

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

18 February 1986 to 4 March 1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPP 81-4 (Acute Eye Irritation)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2,2-dichloro-1-[(3R)-3-methyl-3,4-dihydro-2H-1,4-benzoxazin-4-yl]ethan-1-one; 2,2-dichloro-1-[(3S)-3-methyl-3,4-dihydro-2H-1,4-benzoxazin-4-yl]ethan-1-one

EC Number:

619-372-6

Cas Number:

98730-04-2

Molecular formula:

C11H11Cl2NO2

IUPAC Name:

2,2-dichloro-1-[(3R)-3-methyl-3,4-dihydro-2H-1,4-benzoxazin-4-yl]ethan-1-one; 2,2-dichloro-1-[(3S)-3-methyl-3,4-dihydro-2H-1,4-benzoxazin-4-yl]ethan-1-one

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

4 male and 5 female rabbits

Test system

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

100 mg

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

14 days

Number of animals or in vitro replicates:

9

Details on study design:

CGA154281 (100 mg) was instilled into the conjunctiva! sac of the right eye of 4 male and 5 female rabbits. The eye lids were gently held together for about one second to prevent the loss of material. The left eyes served as a control. The eyes of one male and two female rabbits were rinsed after 30 seconds with tap water for about 60 seconds. The eyes of the remaining rabbits were rinsed with water 24 hours after instillation. Elizabethan collars prevented the rabbits from removing the test article.
One, 24, 48 and 72 hours as well as 7 and 14 days after instillation of the test article the eyes were scored according to the Draize scheme. Additionally ophthal-mological examinations were made pre dose and after 1, 7, and 14 days.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0.22

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: not examined at 7 days

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0.17

Max. score:

2

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: not examined at 7 days

Results 3

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

24/48/72 h

Score:

1.61

Max. score:

3

Reversibility:

fully reversible within: 28 days

Remarks on result:

other: still present in 2 of 6 rabbits at 14 days, not examined 21 days

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.94

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: not examined at 7 days

Irritant / corrosive response data:

When the eyes were rinsed after 30 seconds, only minor signs of ocular irritation, i.e. conjunctival redness up to score 2 and conjunctival chemosis up to score 1 were observed. No signs of irritation were recorded at the 48 hour investigation.
The eyes rinsed after 24 hours displayed slight cornea (score 1) and iris lesions (score 1). Moderate conjunctival redness (up to score 3) and chemosis (up to score 2) were recorded. Beside slight conjunctival redness (score 1) in one male and one female rabbit, no signs of ocular irritation were recorded at 14 days. Both affected rabbits were free of any findings by 28 days.
Additionally, ocular discharge (score 1) was observed in all rabbits 1 and 24 hours after instillation of the test material. Discharge was also noted in one female after 72 and 168 hours, however, this was not considered test-article related, since discharge was also detected in the untreated eye. This female was killed due to poor physical condition on test day 7.

Any other information on results incl. tables

Mean Draize scores of ocular irritation
	Cornea		Iris		Conjunctival  redness		Chemosis
Time
	rinsed	not rinsed	rinsed	not rinsed	rinsed	not rinsed	rinsed	not rinsed
1 h	0	0.33	0	0.17	1.33	2.00	0.67	1.00
24 h	0	0.17	0	0.33	1.00	2.00	0	1.33
48 h	0	0.33	0	0.17	0	1.67	0	1.00
72 h	0	0.17	0	0	0	1.17	0	0.50
14 days	0	0	0	0	0	0.33	0	0
28 days	0	0	0	0	0	0	0	0
Mean 24, 48, 72 h		0.22		0.17		1.61		0.94

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Although there were signs of irritation in the rabbit eye 24, 48 and 72 hours after instillation of benoxacor, these were fully reversible and were not of sufficient severity to warrant classification.

Executive summary:

A single dose of 100 mg was instilled into the conjunctival sac of the right eye of nine rabbits. The left eye remained untreated as a contralateral control.

Eyes of three of the treated animals were rinsed with tap water 30 seconds after instillation. Eyes of the remaining 6 rabbits were rinsed 24 hours after test substance instillation. Reactions were assessed using the standard Draize methods for ocular iirritation.

Data obtained when eyes were rinsed after 30 seconds are not relevant to the the assessment of benoxacor. When the eyes were rinsed after 24 hours, the mean scores for the 24-72 hour post-instilllation period form the basis for assessment of the need to classifiy the test material as an ocular irritant. In this study none of the mean scores and no two individual scores exceeded the threshold values for classification.

While benoxacor did induce some signs of ocular irritation the severity and duration of the reactions were insufficient to necessitate classification.