Pyrimidine, 2,4-dichloro-5-fluoro-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10 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:

no

Test type:

up-and-down procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2,4-dichloro-5-fluoropyrimidine

EC Number:

625-810-7

Cas Number:

2927-71-1

Molecular formula:

C4HCl2FN2

IUPAC Name:

2,4-dichloro-5-fluoropyrimidine

Test material form:

solid

Specific details on test material used for the study:

- Source and lot/batch No.of test material: RZ2-H70762-064- Storage condition of test material: Kept in a room temperature area under nitrogen- Potency: 98.6%; dose calculations were not corrected for potency

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: 7 to 12 weeks- Weight at study initiation: 200-300g (males) 150-250g (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 days ENVIRONMENTAL 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 waster 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 within a 4-hour time span. Administered dose was calculated based on the 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: detailed clinical observations twice daily. Weighing prior to fasting (Day -1), prior to dosing (day 0), and on Days 7 an d 14 - Necropsy of survivors performed: yes evaluation of the carcass and musculoskeletal system; all external surfaces and orifices; cranial cavity and external surfaces of the brain; and thoracic, abdominal, and pelvic cavities with their associated organs and tissues. - 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:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Mortality was noted at 2000 mg/kg with the death of all animals dosed. No mortality, adverse clinical signs, or effects on body weight were noted at 300 mg/kg during the study.

Clinical signs:

other: Prior to death on Day 0, all 2000 mg/kg animals exhibited salivation and 4/6 had decreased activity; one 2000 mg/kg female also had dark material around the nose and mouth. No abnormal clinical signs were present at 300 mg/kg.

Gross pathology:

Gross necropsy observations included haircoat matting around the face and abnormal content in the stomach.

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Systemic toxicity attributable to LSN2431768 was observed during this study, as mortality was noted at 2000 mg/kg with the death of all animals dosed. No mortality, adverse clinical signs, or effects on body weight were noted at 300 mg/kg during the study. Under the conditions of this test, LSN2431768 is considered to be toxic. The Median Lethal Dose is estimated to be greater than 300 mg/kg and less than 2000 mg/kg.

Executive summary:

Under the conditions of this test, LSN2431768 is considered to be acutely toxic. The Median Lethal Dose is estimated to be greater than 300 mg/kg and less than 2000 mg/kg.