4H-Pyrido[1,2-a]pyrimidin-4-one, 3-[2-[4-[(Z)-(2,4-difluorophenyl)(hydroxyimino)methyl]-1-piperidinyl]ethyl]-6,7,8,9-tetrahydro-2-methyl-

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1991-09-25 to 1991-09-28

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

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:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

3-(2-{4-[(Z)-(2,4-DIFLUOROPHENYL)(HYDROXYIMINO)METHYL]PIPERIDIN-1-YL}ETHYL)-2-METHYL-6,7,8,9-TETRAHYDRO-4H-PYRIDO[1,2-A]PYRIMIDIN-4-ONE

EC Number:

603-689-1

Cas Number:

132961-05-8

Molecular formula:

C23H28F2N4O2

IUPAC Name:

3-(2-{4-[(Z)-(2,4-DIFLUOROPHENYL)(HYDROXYIMINO)METHYL]PIPERIDIN-1-YL}ETHYL)-2-METHYL-6,7,8,9-TETRAHYDRO-4H-PYRIDO[1,2-A]PYRIMIDIN-4-ONE

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

- Analytical purity: Base titration revealed 99.8% (w/w) and acid titration revealed 101.6% (w/w).
- Lot/batch No.: BEA011
- Storage condition of test material: at room temperature in closed containers
- Other: The test substance was prepared in Janssen Research Foundation laboratories and passed the specifications of the chemical quality control
department.

Test animals / tissue source

Species:

rabbit

Strain:

other: Cunistar-MDL albino rabbits

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: established stock-farm of Buyens, Lichtaart, Belgium
- Age at study initiation: adult
- Weight at study initiation: ranged between 2.350 and 2.630 kg
- Housing: The rabbits were housed in an air-conditioned room in individual metallic cages. The cages consisted of stainless steel walls and a
wire mesh bottom and front door. The cages were suspended in racks above stainless steel drains with scrapers and sink holes for the collection of faeces and urine.
- Diet: The food consisted of Huybrechts pelleted rabbit food, administered in self-raising hoppers and fed ad libitum throughout the study. The diet met all the nutritional requirements of the test system with guaranteed analysis by the manufacturer.
- Water: free and continuous access to fresh tap-water administered via automatic drinking nipples
- Acclimation period: one week


ENVIRONMENTAL CONDITIONS: no data

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye of each animal served as control

Amount / concentration applied:

TEST MATERIAL
- Amount applied : 0.1 grams/rabbit administered once in the left conjunctival sac
- Concentration: not applicable


VEHICLE: not applicable

Duration of treatment / exposure:

single application

Observation period (in vivo):

3 days, at timepoints: 1, 24, 48, and 72 hours after exposure

Number of animals or in vitro replicates:

Three females

Details on study design:

REMOVAL OF TEST SUBSTANCE: no data
SCORING SYSTEM: Draize

SCORING SYSTEM:
- Draize


TOOL USED TO ASSESS SCORE:
- see below for measures used in calculating eye irritation

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

fully reversible

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritant / corrosive response data:

It was concluded that T 1624, when given to albino rabbits at a single dose of 0.1 g/rabbit by ocular application, produced no eye irritation. The erythema and chemosis noted 1 hour after conjunctival application was no longer present at 24 hours.

During grading, moderate erythema was noted in all rabbits (Draize grading = 2, max 3) 1 hour after conjunctival application, whereas rabbit No.3 also showed slight chemosis (Draize grading = 1, max 4) 1 hour after application. These observations were no longer present at 24 hours. The grading scores for corneal opacity, opacity area, iris, and conjunctiva discharge were 0 at 1 hour. Individual scores were 0 at 1, 24, 48, and 72 hours in all rabbits for the cornea, iris and conjunctiva. The overall irritation index was calculated to be 0.00 and evaluated as no eye irritation.

Other effects:

Body weight remained normal in the rabbits during the 3-day observation period.

Any other information on results incl. tables

Table 1.	Individual grading of eye irritation in rabbits
		Score after
		1 h	24 h	48 h	72 h
Rabbit No. 1
Cornea	opacity	0	0	0	0
	area	0	0	0	0
Iris		0	0	0	0
Conjunctiva
	redness	2	0	0	0
	chemosis	0	0	0	0
	discharge	0	0	0	0
Rabbit No. 2
Cornea	opacity	0	0	0	0
	area	0	0	0	0
Iris		0	0	0	0
Conjunctiva
	redness	2	0	0	0
	chemosis	0	0	0	0
	discharge	0	0	0	0
Rabbit No. 3
Cornea	opacity	0	0	0	0
	area	0	0	0	0
Iris		0	0	0	0
Conjunctiva
	redness	2	0	0	0
	chemosis	1	0	0	0
	discharge	0	0	0	0

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

It was concluded that T 1624, when given to albino rabbits at a single dose of 0.1 g/rabbit by ocular application, produced no eye irritation. The erythema and chemosis noted 1 hour after conjunctival application was no longer present at 24 hours. The test item is therefore considered not to be classified.