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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 guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
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

Constituent 1
Chemical structure
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 levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
< 2 000 mg/kg bw
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:
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
dosing.
Body weight:
All surviving rats gained weight during the first and second weeks of the observation period.
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).

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