Pyrazino[2,1-a]isochinolin-4-on, 4H-, 1,2,3,6,7,11b-hexahydr o-, Diphosphat

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Oct 11 - Dec 06, 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study performed according to OECD TG 423.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Automatically generated during migration to IUCLID 6, no data available

IUPAC Name:

Automatically generated during migration to IUCLID 6, no data available

Test material form:

other: solid

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: F. Winkelmann, Borchen, Germany
- Age at study initiation: 6 to 8 weeks
- Weight at study initiation: 166 (150 - 189) g
- Fasting period before study: 17 hours before until up to 4 hours after treatment
- Housing: separately in type III Makrolon cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 to 22 °C
- Humidity (%): 50 to 66 %
- Photoperiod (hrs dark / hrs light): 12 hour light - 12 hour dark regime

IN-LIFE DATES: From: day 1 To: day 15

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Methocel K4M Premium solution

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 15 and 100 g/L
- Amount of vehicle (if gavage): 20 mL/kg
- Justification for choice of vehicle: excellent vehicle performance in long range historical data


MAXIMUM DOSE VOLUME APPLIED: 20 mL

Doses:

300 and 2000 mg/kg

No. of animals per sex per dose:

300 mg/kg bw: 3 (m) / 3 (f)
2000 mg/kg bw: 3 (f)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: on days 2, 4, 6, 8, 11, 13, and 15 of the experimental part.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology

Statistics:

Standard statistical methods have been applied for data processing.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

At 300 mg/kg bw, all rats survived the observation period. Two female rats, treated with 2000 mg/kg, died 5 hours and two days after treatment. All the other animals survived the observation period.

Clinical signs:

Signs of toxicity were seen immediately after oral administration and continued up to day 3 in the rats treated with 2000 mg/kg. These consisted of: piloerection, retention of feces, lateral and abdominal position, locomotor disturbance, and dyspnea

Body weight:

An inhibition of body weight development was seen in the survived rat treated with 2000 mg/kg on day 2 and 4 ofthe study. The body weight development of all the other rats was inconspicuous.

Gross pathology:

Two of three rats which were treated with 2000 mg/kg died on day 1 or 2, respectively. One rat showed no abnormalities. In the other rat partly watery contents of the small intestine and coprostasis in cecum and colon were seen. All rats which were sacrificed at the end of the study showed no macroscopic abnormalities.

Other findings:

no

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: other: CLP REGULATION (EC) No 1272/2008

Conclusions:

Based on the result of this study, it is concluded that the LD50 of the test material is between 300 and 2000 mg/kg bw after single oral administration in rats.

Executive summary:

Study design

The test material was tested for acute toxicity in rats after single oral administration of 300 and 2000 mg/kg body weight. The study was performed according to the OECD Guideline for Testing of Chemicals, No. 423.

Results

No signs of toxicity were seen in the rats (3 males, 3 females) after treatment with 300 mg/kg of the test item. Signs of toxicity were seen immediately after oral administration and continued up to day 3 in the rats treated with 2000 mg/kg. These consisted of: piloerection, retention of feces, lateral and abdominal position, locomotor disturbance, and dyspnea. At necropsy all rats which were sacrificed at the end of the study showed no macroscopic abnormalities. One of the rats which died showed mild intestinal changes. The body weight development of the rats was inconspicuous during the study.

Conclusion

Based on the result of this study, it is concluded that the LD₅₀ of the test material is between 300 and 2000 mg/kg bw after single oral administration in rats.