1H-Benzimidazole, 6-(2-chloro-5-fluoro-4-pyrimidinyl)-4-fluoro-2-methyl-1-(1-methylethyl)-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

17 October 2013 to 31 October 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

GLP compliance:

yes (incl. QA statement)

Test type:

up-and-down procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

6-(2-chloro-5-fluoropyrimidin-4-yl)-4-fluoro-2-methyl-1-(propan-2-yl)-1H-1,3-benzodiazole

EC Number:

941-461-6

Cas Number:

1231930-42-9

Molecular formula:

C15H13CIF2N4

IUPAC Name:

6-(2-chloro-5-fluoropyrimidin-4-yl)-4-fluoro-2-methyl-1-(propan-2-yl)-1H-1,3-benzodiazole

Specific details on test material used for the study:

- Source and lot/batch No.of test material: RS0-H71422-082- Storage condition of test material: Kept at room temperature under nitrogen

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: 8 weeks- Weight at study initiation: 214-271g (males) 180-197g (females)- Fasting period before study: Overnight prior to dosing- Housing: Polycarbonate cages containing appropriate bedding with an automatic watering valve- Diet (e.g. ad libitum): Standard certified commerical laboratory diet- Water (e.g. ad libitum): Municipal tap water- Acclimation period: 7 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 21-23- Humidity (%): 50-59- Air changes (per hr): minimum of 10- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

An appropriate quantity of test material was added to the requisite amount of de-ionised water and mixed manually until visibly homogeneous. Test material was administered orally as either a single dose (dose volume ≤20 mL/kg) or divided into two seperate doses (dose volume >20 mL/kg) administered with a 4-hour time span.Administered dose was calculated based on weight of the animal on the day of dosing.

Doses:

300 mg/kg body weight2000 mg/kg body weight

No. of animals per sex per dose:

300 mg/kg: 3 males and 3 females2000 mg/kg: 3 males and 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days- Frequency of observations and weighing: Frequency of observations and weighing: detailed clinical observations twice daily. Weighing prior to fasting (Day -1) prior to dosing (day 0), and on Days 7 and 14- Necropsy of survivors performed: No- Other examinations performed: clinical signs, body weight

Statistics:

Body weight means and standard deviations were calculated separately for males and females

Results and discussion

Preliminary study:

Not relevant, this is not a fixed dose study

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No morality occurred during the study

Clinical signs:

other: No abnormal clinical signs were present at 300 mg/kg and 2000 mg/kg

Gross pathology:

As no morality occurred during the study complete necropsy examinations were not undertaken

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this test, LSN2833975 is considered to be non-toxic. The Median Lethal Dose is estimated to be greater than 2000 mg/kg.

Executive summary:

The single-dose oral toxicity of LSN2833975 was evaluated in Sprague Dawley rats. Two groups of rats (3 males and 3 females per group) were given a single oral dose of the test article at 300 mg/kg or 2000 mg/kg body weight. Following dosing, the rats were observed daily and weighed weekly. There were no test article-related clinical signs, effects on body weight, or gross necropsy findings observed at 300 mg/kg and 2000 mg/kg. Under the conditions of this test, LSN2833975 is considered to be non-toxic. The Median Lethal Dose is estimated to be greater than 2000 mg/kg.