1H-Pyrazolo[3,4-c]pyridine-3-carboxylic acid, 4,5,6,7-tetrahydro-1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxo-1-piperidinyl)phenyl]-, ethyl ester

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

September 9 to 30, 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study was conducted according to OECD and in accordance with GLP. The study material is well characterize

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

GLP compliance:

yes

Remarks:

ENV/MC/CHEM(98)17 and 1999/11/EC

Test type:

acute toxic class method

Test material

Test material information

Constituent 1

Reference substance name:

ethyl 1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxopiperidin-1-yl)phenyl]-1H,4H,5H,6H,7H-pyrazolo[3,4-c]pyridine-3-carboxylate

EC Number:

700-890-7

Cas Number:

503614-91-3

Molecular formula:

C27 H28 N4 O5

IUPAC Name:

ethyl 1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxopiperidin-1-yl)phenyl]-1H,4H,5H,6H,7H-pyrazolo[3,4-c]pyridine-3-carboxylate

Details on test material:

Powder

Test animals

Species:

rat

Strain:

other: Hsd:Sprague-Dawley(CD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan UK Ltd, Bicester, Oxon, England
- Age at study initiation: 5 - 7 weeks
- Weight at study initiation: 103 to 136 g
- Fasting period before study: overnight prior to, and 4 hours after, dosing.
- Housing: 3 of the same sex in metal cages with wire mesh mesh floors
- Diet: Standard lab rodent diet, ad libitum
- Water: tap water, ad libitum
- Acclimation period: minimum of 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3°C
- Humidity: 40-70 %
- Photoperiod (hrs dark / hrs light):12 hrs artificial light (06:00 - 18:00 hours in each 24hr period.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 1% methyl cellulose solution

Details on oral exposure:

by oral gavage using a plastic syringe and catheter (8 ch).

Doses:

dose level: 2,000 mg/kg

No. of animals per sex per dose:

3 females plus 3 males per dose

Control animals:

no

Details on study design:

The cages of the rats were checked at least twice daily for any mortalities.
Animals were observed soon after dosing and at frequent intervals for the remainder of day 1. On subsequent days animals were observed once in the morning and at the end of each experimental day (with the exception of day 15 - morning only).
All animals were observed for 14 days after dosing.

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths following a single oral gavage dose to a group of 6 rats (3 male/3 female) at a dose level of 2,000mg/kg bodyweight.

Clinical signs:

other: 1 female, on day 1, showed signs of piloerection. Recovery was complete by day 2.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral median lethal dose (LD50) of the test material was greater than 2000 mg/kg bodyweight

Executive summary:

The acute oral lethal dose (LD50) to rats of BMS 589154 -01 was demonstrated ot be greater than 2,000 mg/kg bodyweight.