5-bromo-4-chloro-6-cyclopropylpyrimidine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Nov. 2018 - Feb. 2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Report date:

2019

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:

given by compliance statement and signature

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

5-bromo-4-chloro-6-cyclopropylpyrimidine

EC Number:

823-376-5

Cas Number:

27192-21-8

Molecular formula:

C7H6BrClN2

IUPAC Name:

5-bromo-4-chloro-6-cyclopropylpyrimidine

Test material form:

solid: particulate/powder

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.

Environmental conditions
The animals were kept in the following conditions except for short periods of time where experimental procedures dictated otherwise.
The animals were housed in groups of up to four 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. The water was periodically analysed for specific contaminants.
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. Each batch of diet had been analysed for specific constituents and contaminants by the manufacturer.
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. Daily recordings of maximum and minimum temperature and humidity were made.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

methylcellulose

Remarks:

dispersed in 1% w/v aqueous methyl cellulose, dose volume of 10 mL/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:

Sighting Study (preliminary test)
300, 2000 mg/kg bw

Main Study
300 mg/kg bw

No. of animals per sex per dose:

2000 mg/kg bw: 1 female
300 mg/kg bw: 4 female

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.

Results and discussion

Preliminary study:

In the preliminary study female fasted rats were given the test article as a single dose by oral
gavage at a dose level of 300 and 2000 mg/kg.

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

300 mg/kg bw

Based on:

test mat.

Mortality:

1 animal at 2000 mg/kg bw

Clinical signs:

other: Clinical signs noted in the animal treated at 2000 mg/kg were decreased activity 1 hour after dosing and tonic convulsions 2 hours after dosing. As the convulsions lasted for over 2 minutes, the animal was humanely killed. Piloerection was noted 2 and 3 h

Gross pathology:

No abnormalities were noted at necropsy except for pale kidneys noted in two animals treated at 300 mg/kg.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The test article, BI 730357 Bromchlor / IN 79479, 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).
LD50 > 300 < 2000 mg/kg bw.