1H-Purine-2,6-dione, 8-bromo-7-(2-butyn-1-yl)-3,7-dihydro-3-methyl-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

11 Sep 2003 - 02 Oct 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2004

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

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

8-bromo-7-(but-2-yn-1-yl)-3-methyl-2,3,6,7-tetrahydro-1H-purine-2,6-dione

EC Number:

613-975-8

Cas Number:

666816-98-4

Molecular formula:

C10-H9-Br-N4-O2

IUPAC Name:

8-bromo-7-(but-2-yn-1-yl)-3-methyl-2,3,6,7-tetrahydro-1H-purine-2,6-dione

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

other: CrlGlxBrlHan:WI (SPF quality)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH, Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: Approximately 7 weeks
- Weight at study initiation: males 173-174 g, females 126-138 g
- Fasting period before study: Food was available ad libitum, but was withdrawn in the afternoon of Day-1 until administration

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 45-75%
- Air changes (per hr): approximately 12 air changes per hour
- Photoperiod (hrs dark / hrs light): 12/12 hours

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 0.5% aqueous hydroxyethylcellulose (Natrosol® 250 HX)

Details on oral exposure:

In the morning of Day 1, a single oral administration of f BI 1344 BZ/CD 164 formulation by gavage was performed. The administration volume was 10mL/kg in each group.

Doses:

200mg/kg and 2000mg/kg

No. of animals per sex per dose:

3 male and 6 female

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
Mortality and the general health condition of the animals were inspected at least twice
daily in all groups (all animals). During the pretest period, on weekends and on non-working days the animals were inspected at least once daily.

The health status of the animals was checked at supply. The overall appearance and
behavior of each animal was inspected at least twice daily. Any abnormalities were
recorded with regard to onset, duration and, if possible, intensity. On weekends and on
non-working days clinical observations were performed in the morning only.

The body weights of all animals were recorded on Days 1, 2, 8 and 15.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

no mortality occurred

Clinical signs:

other:

Body weight:

other body weight observations

Remarks:

Keeping animals without food over night resulted in reduced body weight on Day 1. Thereafter, development of body weight during the observation period was typical for the strain of rats used at this age and not influenced by administration of different doses of the test item.

Gross pathology:

No necropsy findings were noted.

Applicant's summary and conclusion

Interpretation of results:

other: not classified acc. CLP

Conclusions:

The approximate lethal dose (ALD) for BI 1344 Alkin is above 2000mg/kg for both male and female rats.