4-[2-(2-amino-4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoic acid

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

18 November 1998 to 16 December 1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Report date:

1999

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

4-[2-(2-amino-4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoic acid

EC Number:

429-790-9

EC Name:

4-[2-(2-amino-4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoic acid

Cas Number:

137281-39-1

Molecular formula:

Hill formula: C15 H14 N4 O3 CAS formula: C15 H14 N4 O3

IUPAC Name:

4-(2-{2-amino-4-oxo-3H,4H,7H-pyrrolo[2,3-d]pyrimidin-5-yl}ethyl)benzoic acid

Test material form:

solid: particulate/powder

Details on test material:

- Compound 202723
- Storage condition of test material: In the dark at ambient temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: outside vendor
- Age at study initiation: 6 -8 weeks old
- Weight at study initiation: 149-186 grams
- Fasting period before study: Overnight prior to dosing


- Housing: Polypropylene cages with stainless steel grid tops and bottoms
- Diet: ad libitum supply of 'Rat and Mouse No. 1 Maintenance Diet' animal feed
- Water: ad libitum supply of domestic mains water
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS
- Temperature : 19 -20 °C
- Humidity: 39 -54%
- Air changes (per hr): minimum of 15
- Photoperiod (hrs dark / hrs light): 12 hr light/dark cycle (light hours 07:00-19:00)

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

distilled

Details on oral exposure:

An appropriate quantity of test material was added to the requisite amount of distilled water and mixed manually until visibly homogeneous. Test material was administered orally in a single dose by means of a gavage at a constant dose volume of 10ml/kg. Administered dose was calculated based on the weight of the animal on the day of dosing.

Doses:

Dose ranging treatment levels:
500 mg/kg
2000 mg/kg
Based on the results of the dose ranging, the main study was conducted at a dose level of 2000 mg/
kg.

No. of animals per sex per dose:

Preliminary sighting study: 0 (male)
Preliminary sighting study: 2 (female)
Main study: 5 (male)
Main study: 5 (female)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: Daily
- Frequency of body weight measurements: Dose ranging study - day of dosing (Day 1) only & Main s tudy - day of dosing (Day1), Day 2, 3,4, 8 and 15
- Necropsy of survivors performed: yes, on main study animals only - examination of the thoracic and abdominal organs and tissues in situ.
- Clinical observations: All animals were examined for reaction to treatment. The onset, intensity and duration of any signs were recorded.

Statistics:

No formal statistical analysis was conducted

Results and discussion

Preliminary study:

No adverse clinical signs were noted in the preliminary sigthting study conducted at fixed dose levels of 500mg/kg and 2000 mg/kg in female animals.

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

discriminating dose

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred

Clinical signs:

There were no adverse clinical signs noted during the observation period.

Body weight:

Body weight performance was unaffected by treatment

Gross pathology:

Effects on organs:
None

Other findings:

None

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 rat > 2000 mg/kg

Executive summary:

This study investigated the acute oral toxicity of compound 202723 after a single oral gavage administration to Sprague-Dawley rats.

Following preliminary dose ranging, at 500 and 2000 mg/kg, 5 male and 5 female rats, included in the main study, received 2000mg/kg. The test material was administrered using distilled water as a vehicle, at a dose volume of 10ml/kg. The animals were observed daily for viability and signs of reaction to treatment for up to 14 days after dosing. Body weights were recorded on Days 1,2,3,4,8 and 15. A necropsy examination was performed after death on all main study animals.

There were no premature decedents or adverse clinical signs during the study. Body weight performance was unaffected by treatment and no abnormalities were noted at necropsy.

Under the conditions of the study, following a single oral administration of intermediate 202723 to Sprague-Dawley rats, no mortality and no toxicity occurred at 2000mg/kg.