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

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2004-10-29 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.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal 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

Species:

rabbit

Strain:

New Zealand White

Remarks:

rbt, Crl:KBL(NZW)BR

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 24 weeks
- Weight at study initiation: 4.96 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: 20°C
- Humidity: 39 - 62 %
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Remarks:

some drops of Aqua pro injectione to ensure good contact with the skin

Controls:

not required

Amount / concentration applied:

The test material was administered undiluted with 0.5 g onto 6 cm² patches.

Duration of treatment / exposure:

4 h

Observation period:

up to day 8

Number of animals:

3 females

Details on study design:

SCORING SYSTEM: according to Draize

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 4

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 5

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 6

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 7

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 8

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

After a single application to the intact dorsal skin of rabbits, for 4 hours under semiocclusive conditions, no signs of irritation were observed at the treated areas.

Other effects:

- Other adverse local effects: none
- Other adverse systemic effects: No signs of clinical toxicity were detected. All animals survived the observation period.

Any other information on results incl. tables

Table 1 individual local findings after 4 h exposure under semiocclusive conditions

Animal No.		Local findings on day
		1	2	3	4	5	6	7	8
		(1 h)	(24 h)	(48 h)	(72 h)
15	Erythema	0	0	0	0	0	0	0	0
	Edema	0	0	0	0	0	0	0	0
19	Erythema	0	0	0	0	0	0	0	0
	Edema	0	0	0	0	0	0	0	0
21	Erythema	0	0	0	0	0	0	0	0
	Edema	0	0	0	0	0	0	0	0

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study no skin irritation potential could be detected with the test item.

Executive summary:

The study was performed according to the OECD Guideline for Testing of Chemicals, No. 404, the annex to Directive 92/69 EEC, and the recommendations of DRAIZE (1959). To test for primary skin irritation, 0.5 g of the test material was mixed with some drops of Aqua pro injectione to ensure good contact with the skin. Afterwards the test material was spread onto 6 cm² patches and applied to the intact skin of previously shaven rabbits for a 4 hours period under semiocclusive conditions. The study was started as an initial test with one animal and followed by the confirmatory test with two further animals. The first examination of the treated skin sites followed 1 hour after removal of the patches. Thereafter, examinations were performed daily for further 7 days.
Under the conditions of the present study no signs of irritation were seen.

Evaluation of all animals (mean score)

Day (after treatment)	1 (1 hour)	2 (24 hours)	3 (48 hours)	4 (72 hours)
Erythema	0	0	0	0
Edema	0	0	0	0

Evaluation of each animal

	Mean Score (24, 48, 72 hours)			Max Score (24, 48, 72 hours)
Animal No.	15	19	21	15	19	21
Erythema	0	0	0	0	0	0
Edema	0	0	0	0	0	0

Based on the results of this study, the test item is not considered to be irritating to skin.