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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2004-11-12 to 2005-02-03

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.3 (Acute Toxicity (Dermal))

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

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:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 8-9 weeks
- Weight at study initiation: 229 g (range from 209 to 249 g).
- Fasting period before study: no
- Housing: separately in type III Makrolon cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 to 23 °C
- Humidity: 44 to 57 %
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

water

Remarks:

Aqua pro injection, Merck KGaA, Darmstadt; Batch 189.

Details on dermal exposure:

Preparation: Before application, the test material was mixed with some drops of Aqua pro injectione and ground in a mortar using pestle. These test material were spread on the shaven skin.

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5m / 5f

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: for at least 6 hours after administration and then checked daily
- Body weight: on days 2, 4, 6, 8, 11, 13, and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: gross pathology

Statistics:

The body weight data were recorded with the PC-program “AKUDAT“ The statistical evaluations of the body weight were carried out with the PC-program “TOX 511 A“, developed by the Institute of Toxicology of Merck KGaA, Darmstadt. The body weight development of each rat and group was determined. The group mean value was calculated for each measurement and printed on tables.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0

Clinical signs:

other: Signs of toxicity related to dose levels: No signs of toxicity were detected @2000 mg/kg bw.

Gross pathology:

Effects on organs:
At necrospy, no organ alterations were seen.

Any other information on results incl. tables

Table 1 Summary of mortalities

Sex	LD50 on days 1 + 8+ 15
M + F	>2000 mg/kg bw

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the result of this study, the test item can be considered to have no acute toxic potential and to have a LD50 value higher than 2000 mg/kg bw after dermal application to rats.

Executive summary:

The study was performed accorting OECD TG 402. The test was performed as a limit test using a dose of 2000 mg/kg body weight. Directly before administration the test material was moistened and spread on the shaven skin in an area of 6 x 6 cm, and covered with a gauze patch. This was kept in place by a self-adhesive fabric (Fixomull® stretch, Beiersdorf). The time of exposure was 24 hours. Then the gauze and adhesive fabric were removed and any remaining test material was wiped off carefully. No signs of toxicity were detected in the rats (5 males and 5 females) after treatment with 2000 mg/kg bw. There were no deaths during the course of the study. The gross pathological examination revealed no organ alterations.

Based on the result of this study, the test material can be considered to have no acute toxic potential and to have a LD50 value higher than 2000 mg/kg bw after dermal application to rats.