(4-cyclopropyl-6-methyl-pyrimidin-5-yl)boronic acid

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10. January - 7 February 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2020

Report date:

2020

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: Method B1 bis of Council Regulation (EC) No 440/2008

GLP compliance:

yes

Remarks:

including Compliance Statement and signatur page

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

(4-cyclopropyl-6-methyl-pyrimidin-5-yl)boronic acid

EC Number:

826-639-2

Cas Number:

1817776-86-5

Molecular formula:

C8 H11 B N2 O2

IUPAC Name:

(4-cyclopropyl-6-methyl-pyrimidin-5-yl)boronic acid

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

other: Crl:Wl(Han)

Sex:

female

Details on test animals or test system and environmental conditions:

Female (nulliparous, non-pregnant) Crl:WI(Han) strain rats
Supplier: Charles River (UK) Ltd.
All animals were given a clinical inspection for ill health on arrival and a sample was weighed.

Body weight range of 158 to 201 g on Day 1.
Approximately 8 to 10 weeks old on Day 1.

Environmental Conditions
- Mains water was provided ad libitum via water bottles
- 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.
- temperature and humidity ranges were 20 to 24°C and 45 to 65% respectively.
- Fluorescent lighting 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 10mL/kg

Details on oral exposure:

Doses were administered orally, by gavage, using plastic syringes and rubber catheters. Each
rat was dosed once on Day 1, by passing the tip of a catheter along the oesophagus and
instilling the test article into the gastric lumen.

Doses:

300 mg/kg bw
2000 mg/kg bw

No. of animals per sex per dose:

4 females per 300mg/kg (main study)
1 female per 300 mg/kg and 1 female per 2000 mg/kg (primary 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
from the fifth to last day of the observation period. Individual records of clinical signs and
times of death were maintained for each treated rat.
- Rats were weighed on Day-1 (day before dosing) and on Days 1, 4, 8 and 15. Decedent
carcass weights were also recorded prior to necropsy.
- Rats surviving treatment were killed on Day 15.

Results and discussion

Preliminary study:

A preliminary test was performed to establish a dosing regimen for the main test. Dosing was
as follows:300 mg/kg bw, 2000 mg/kg bw

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50

Effect level:

< 2 000 mg/kg bw

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 mg/kg bw

Mortality:

The animal dosed at 2000 mg/kg was found dead on Day 5. No deaths were noted in animals
treated at 300 mg/kg.

Clinical signs:

other: Piloerection was noted in the animal dosed at 2000 mg/kg on Days 2, 3 and 4. Hunched posture, decreased activity and piloerection were noted in one animal dosed at 300 mg/kg. The signs developed from one hour after dosing and lasted up to four hours after

Gross pathology:

No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The test article, IN 79056, was classified as Category 4 in respect of its acute oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).