4H-Pyrazino[2,1-a]isoquinolin-4-one, 2-acetyl-1,2,3,6,7,11b-hexahydro-

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2004-11-18 to 2005-02-10

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

470-180-7

EC Name:

-

Cas Number:

61196-40-5

Molecular formula:

C14H16N2O2

IUPAC Name:

2-acetyl-1H,2H,3H,4H,6H,7H,11bH-pyrazino[2,1-a]isoquinolin-4-one

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Remarks:

rbt, Crl:KBL(NZW)

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: 28- 29 weeks
- Weight at study initiation: 4.78 kg
- Housing: separately in special rabbit cages (manufacturer: Becker; type K99/30 KU, floor area about 5400 cm2, a shelter with an integrated sitting board of about 1820 cm2; overall height: 60 cm)
- Diet: ad libitum
- Water:ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 17-18 °C
- Humidity: 46 - 60 %
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 / 12

Test system

Vehicle:

unchanged (no vehicle)

Remarks:

Before application, the test material was ground in a mortar using a pestle.

Controls:

not required

Amount / concentration applied:

100 mg

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

3 females

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: no

SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: fluorescein

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

24/48/72 h

Score:

1.67

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 2

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

24/48/72 h

Score:

1.67

Max. score:

3

Reversibility:

fully reversible within: 6 days

Results 3

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 5 days

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Results 5

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Results 6

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 7

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Results 8

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Results 9

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 5 days

Results 10

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 11

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 12

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritant / corrosive response data:

Reversibility of any observed effect: Changes fully reversible within 7 days

Other effects:

No signs of irritation could be observed at the iris. The cornea showed scattered or diffuse areas of opacity (score 1) at the first reading up to day 4 of the experimental part. The conjunctivae showed redness (scores 1 and 2) and chemosis (scores 1 to 4) from the first reading up to experimental day 6, maximally. Furthermore discharge (scores 2 and 3) was seen from the first reading up to day 3.
Thereafter no signs of irritation were observed. The untreated eyes were unchanged.

Any other information on results incl. tables

Table 1 Individual findings

		Mean score (24, 48, and 72 hours)			Maximum value (24, 48, or 72 hours)
Animal No		17	18	20	17	18	20
Cornea	A	0.33	0.67	1.00	1	1	1
Iris	A	0.00	0.00	0.00	0	0	0
Conjunctivae	A	1.67	1.67	1.00	2	2	1
	B	1.67	0.33	0.00	4	1	0

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of this study the test material is not regarded as irritant to the eyes.

Executive summary:

To test for primary eye irritation, 0.1 g of the solid test material was applied into the conjunctival sac of rabbits according to OECD TG 405. The first examination of the eyes followed 1 hour after instillation. The examinations were performed daily for further 7 days. No signs of irritation could be observed at the iris. The cornea showed scattered or diffuse areas of opacity (score 1) at the first reading up to day 4 of the experimental part. The conjunctivae showed redness (scores 1 and 2) and chemosis (scores 1 to 4) from the first reading up to experimental day 6, maximally. Furthermore discharge (scores 2 and 3) was seen from the first reading up to day 3. Thereafter no signs of irritation were observed. The untreated eyes were unchanged.

Evaluation of all animals (mean score)

Day	1	2	3	4
(after treatment)	(1 hour)	(24 hours)	(48 hours)	(72 hours)
Cornea	1.00	1.00	0.67	0.33
Iris	0.00	0.00	0.00	0.00
Redness	1.33	1.67	0.33	0.00
Chemosis	3.00	1.67	0.33	0.00

Evaluation of each animal

	Mean score			Max Score
	(1, 24, 48, 72 hours)			(1, 24, 48, 72 hours)
Animal No.	1	2	3	1	2	3
Cornea	0.33	0.67	1.00	1	1	1
Iris	0.00	0.00	0.00	0	0	0
Redness	1.67	1.67	1.00	2	2	1
Chemosis	1.67	0.33	0.00	4	1	0

Based on the results of this study the test material is not regarded as irritant to the eyes.