2-Chloro-8-((S)-1-cyclopropyl-ethyl)-6-[(5-methanesulfonyl-pyridin-2-ylmethyl)-amino]-8Hpteridin-7-one

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

21 December 2016 - 31 January 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-chloro-8-[(1S)-1-cyclopropylethyl]-6-{[(5-methanesulfonylpyridin-2-yl)methyl]amino}-7,8-dihydropteridin-7-one

EC Number:

825-281-4

Cas Number:

1817775-66-8

Molecular formula:

C18H19ClN6O3S

IUPAC Name:

2-chloro-8-[(1S)-1-cyclopropylethyl]-6-{[(5-methanesulfonylpyridin-2-yl)methyl]amino}-7,8-dihydropteridin-7-one

Test material form:

solid: bulk

Test animals

Species:

rat

Strain:

other: Crl:WI(Han)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
-Female (nulliparous, non-pregnant) Crl:WI(Han) strain rats were obtained from Charles
River (UK) Ltd., Margate.
-The rats were in a body weight range of 161 to 200 g on Day 1.
-Rats were approximately 8 to 10 weeks old on Day 1

CONDITIONS
-The animals were housed in groups of up to five in cages that conformed to the ‘Code of
Practice for the Housing and Care of Animals Bred, Supplied or Used for Scientific
Purposes’ (Home Office, London, 2014).
-Mains water was provided ad libitum via water bottles.
-Throughout the study the animals had access to 5LF2 EU Rodent Diet 14%, which was freely
available to the animals at all times, except for a period of fasting from the evening of the day
prior to dosing (Day-1) until approximately 3 hours after dosing.
-The animal rooms were designed to permit 15 to 20 air changes per hour. The target
temperature and humidity ranges were 20 to 24°C and 45 to 65% respectively.
-Fluorescent lighting was controlled automatically to give a cycle of 12 hours light and
12 hours dark.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

methylcellulose

Remarks:

1% w/v at a dose volume of 10 mL/kg.

Doses:

300 mg/kg and 2000 mg/kg (sighting study only)
2000 mg/kg (main study)

No. of animals per sex per dose:

1 female per 300 mg/kg (sighting study)
1 female per 2000 mg/kg (sighting study)
4 female per 2000 mg/kg (main study)

Control animals:

no

Details on study design:

All animals were observed at the beginning and the end of the working day for signs of ill
health or overt toxicity.

Treated rats were observed closely for clinical signs of reaction to treatment. Clinical signs
were recorded immediately post-dose, at approximately 15 and 30 minutes post-dose, hourly
between 1 and 4 hours post-dose (inclusive), twice daily on Days 2, 3 and 4 and once daily

Rats were weighed on Day-1 (day before dosing) and on Days 1, 4, 8 and 15.
from the fifth to last day of the observation period. Individual records of clinical signs were
maintained for each treated rat.

Results and discussion

Preliminary study:

1 female per 300 mg/kg (sighting study)
1 female per 2000 mg/kg (sighting study)

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other: Hunched posture and piloerection were noted on Day 2 in the animal treated at 300 mg/kg. No other clinical signs were seen.

Gross pathology:

No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:

other: not classified according to CLP

Conclusions:

The acute median lethal oral dose of BI 740293 to rats was found to exceed 2000 mg/kg.
The test material was considered to have no significant acute toxic risk in respect of its acute
oral toxicity and did not meet the criteria for classification according to the Globally
Harmonized System of Classification and Labelling of Chemicals (GHS).